title: Effects of the Converting Enzyme Inhibitor Quinapril (CI‐906) on Blood Pressure, Renin‐Angiotensin System, and Prostanoids in Essential Hypertension A comparative study of lisinopril and atenolol on low degree urinary albumin excretion, renal function and haemodynamics in uncomplicated, primary hypertension Placebo-controlled comparison of spirapril at 6, 12 and 24 mg/day in mild to severe essential hypertension. The incidence of cough: a comparison of lisinopril, placebo and telmisartan, a novel angiotensin II antagonist. Telmisartan Cough Study Group. Dose finding studies with imidapril--a new ACE inhibitor. Unchanged neurogenic vasoconstrictor response after exercise during angiotensin converting enzyme inhibition with fosinopril. Co-administration of an ACE-inhibitor (moexipril) and hormonal replacement therapy in postmenopausal women The Effect of Cilazapril, a New Angiotensin Converting Enzyme Inhibitor, on Peak and Trough Blood Pressure Measurements in Hypertensive Patients Comparative study of once-daily administration of captopril 50 mg, hydrochlorothiazide 25 mg and their combination in mild to moderate hypertension. Do trandolapril and indomethacin influence renal function and renal functional reserve in hypertensive patients? The 24 h blood pressure responses of hypertensives to a once-a-day cilazapril regimen. Ketanserin and captopril interaction in the treatment of essential hypertensives Perindopril as monotherapy in hypertension: A multicenter comparison of two dosing regimens Comparative effects of quinapril, atenolol, and verapamil on blood pressure and forearm hemodynamics during handgrip exercise. Does blood pressure reduction necessarily compromise cardiac function or renal hemodynamics? Effects of the angiotensin-converting enzyme inhibitor quinapril. The antihypertensive efficacy and tolerability of a low dose combination of ramipril and felodipine ER in mild to moderate essential hypertension. Effects of moderate salt restriction alone and in combination with cilazapril on office and ambulatory blood pressure. Valsartan, a new angiotensin II antagonist for the treatment of essential hypertension: efficacy and safety compared with placebo and enalapril Captopril and Nifedipine Interactions in the Treatment of Essential Hypertensives: A Crossover Study Efficacy, tolerance and hormonal effects of a new oral angiotensin converting enzyme inhibitor, ramipril (HOE 498), in mild to moderate primary hypertension. Short report: Ramipril and hydrochlorothiazide combination therapy in hypertension: a clinical trial of factorial design Use of the factorial design and quadratic response surface models to evaluate the fosinopril and hydrochlorothiazide combination therapy in hypertension. Once-daily treatment of patients with hypertension: a placebo-controlled study of amlodipine and benazepril vs amlodipine or benazepril alone Brazilian multicenter study on efficacy and tolerability of trandolapril in mild-to-moderate essential arterial hypertension. EMBATHE substudy with ambulatory blood pressure monitoring. Combined enalapril and felodipine extended release (ER) for systemic hypertension. Enalapril-Felodipine ER Factorial Study Group. Lisinopril versus hydrochlorothiazide in obese hypertensive patients: a multicenter placebo-controlled trial. Treatment in Obese Patients With Hypertension (TROPHY) Study Group. Are angiotensin converting enzyme inhibition and aldosterone antagonism equivalent in hypertensive patients over fifty? Indomethacin does not attenuate the hypotensive effect of trandolapril. Placebo‐controlled comparison of the efficacy and tolerability of once‐daily moxonidine and enalapril in mild‐to‐moderate essential hypertension Effect of Spirapril and Hydrochlorothiazide on Platelet Function and Euglobulin Clot Lysis Time in Patients with Mild Hypertension Monotherapy of essential hypertension with a converting-enzyme inhibitor. The influence of long-term ACE inhibitor treatment on circulatory responses to stress in human hypertension. Preventing increases in early-morning blood pressure, heart rate, and the rate-pressure product with controlled onset extended release verapamil at bedtime versus enalapril, losartan, and placebo on arising. Lisinopril is neutral to insulin sensitivity and serum lipoproteins in essential hypertensive patients Tricenter assessment of the efficacy of the ACE inhibitor, moexipril, by ambulatory blood pressure monitoring. The effect of perindopril and hydrochlorothiazide alone and in combination on blood pressure and on the renin-angiotensin system in hypertensive subjects ANGIOTENSIN II BLUNTS, WHILE AN ANGIOTENSIN‐CONVERTING ENZYME INHIBITOR AUGMENTS, REFLEX SYMPATHETIC INHIBITION IN HUMANS* Evaluation of the Efficacy and Tolerability of a Low-Dose Combination of Isradipine and Spirapril in the First-Line Treatment of Mild to Moderate Essential Hypertension Cilazapril inhibits vascular responses to baroreflex-stimulated sympathetic neural activity in hypertensive patients. Hemodynamic effects of quinapril, a novel angiotensin‐converting enzyme inhibitor Placebo-controlled comparison of the efficacy and tolerability of once-daily moxonidine and enalapril in mild-to-moderate essential hypertension. T-Lymphocyte and Plasma Angiotensin-Converting Enzyme Activity During Enalapril and Losartan Administration in Humans [Effects of captopril on the cerebral blood flow in the hypertensive aged subjects]. 24‐hour blood pressure profiles in hypertensive patients administered ramipril or placebo once daily: Magnitude and duration of antihypertensive effects Antihypertensive effect of enalapril as first-step treatment of mild and moderate uncomplicated essential hypertension. Evaluation by two methods of blood pressure measurement. Angiotensin-converting enzyme inhibition in mild hypertension with concomitant diseases and therapies: an efficacy, safety, and compatibility study of novel design, the Perindopril Therapeutic Safety Study. Platelet Function During Antihypertensive Treatment with Quinapril, a Novel Angiotensin Converting Enzyme Inhibitor Antihypertensive efficacy and tolerability of captopril in the elderly: comparison with hydrochlorothiazide and placebo in a multicentre, double-blind study. Evaluation of the antihypertensive efficacy and tolerability of moexipril, a new ACE inhibitor, compared to hydrochlorothiazide in elderly patients The effects of the long‐acting angiotensin–converting enzyme inhibitor cilazapril on casual, exercise, and ambulatory blood pressure Evaluation of the dose-effect relationship of a new ace inhibitor (perindopril) by an automatic blood pressure recorder. Treatment of hypertension in the elderly: effects on blood pressure, heart rate, and physical fitness. Effects of verapamil and trandolapril in the treatment of hypertension. Trandolapril Study Group. Treatment of hypertension with enalapril and hydrochlorothiazide or enalapril and atenolol: contrasts in hypotensive interactions. Quinapril and hydrochlorothiazide combination for control of hypertension: assessment by factorial design. Quinapril Investigator Group. The effect of an endothelin-receptor antagonist, bosentan, on blood pressure in patients with essential hypertension. Bosentan Hypertension Investigators. Single‐Dose and Steady‐State Pharmacokinetics and Pharmacodynamics of Perindopril in Hypertensive Subjects Renin status does not predict the anti-hypertensive response to angiotensin-converting enzyme inhibition in African–Americans Trandolapril does not improve insulin sensitivity in patients with hypertension and type 2 diabetes: a double-blind, placebo-controlled crossover trial. Comparison of candesartan versus enalapril in essential hypertension. Italian Candesartan Study Group. Antihypertensive Efficacy of Cilazapril 2.5 and 5.0 mg Once‐Daily Versus Placebo on Office Blood Pressure and 24‐Hour Blood Pressure Profile Insulin sensitivity in hypertensive Type 2 diabetic patients after 1 and 19 days' treatment with trandolapril. Twenty-four hour blood pressure effect of once-daily lisinopril, enalapril, and placebo in patients with mild to moderate hypertension. Comparison of Efficacy of Spirapril and Enalapril in Control of Mild-to-Moderate Hypertension Enalapril and atenolol in essential hypertension: attenuation of hypotensive effects in combination. Verapamil SR and trandolapril combination therapy in hypertension--a clinical trial of factorial design. German Hypertension Study Group. Felodipine-metoprolol combination tablet: a valuable option to initiate antihypertensive therapy? Antihypertensive profiles with ascending dose combinations of ramipril and felodipine ER. A randomised, placebo-controlled, double-blind, crossover study of losartan and enalapril in patients with essential hypertension Post-exercise reduction in blood pressure in hypertensive subjects: effects of angiotensin converting enzyme inhibition. Therapeutic safety of perindopril in the treatment of mild hypertension with concomitant nephropathy. Evaluation of blood pressure response to the combination of enalapril (single dose) and diltiazem ER (four different doses) in systemic hypertension. Captopril at 50 mg as well as at 100 mg once a day reduces blood pressure for up to 24 h: a double‐blind randomized crossover study in mild to moderate hypertensives Additive effects of verapamil and enalapril in the treatment of mild to moderate hypertension. Differing mechanisms of action of angiotensin-converting enzyme inhibition in black and white hypertensive patients. The Trandolapril Multicenter Study Group. Combined Versus Single Effect of Fosinopril and Hydrochlorothiazide in Hypertensive Patients Racial differences in response to low-dose captopril are abolished by the addition of hydrochlorothiazide. Lack of effect of short-term lisinopril administration on left ventricular filling dynamics in hypertensive patients with diastolic dysfunction. Comparison of the fixed combination of enalapril/diltiazem ER and their monotherapies in stage 1 to 3 essential hypertension. Evaluation of the antihypertensive effect of once-a-day trandolapril by 24-hour ambulatory blood pressure monitoring. The Italian Trandolapril Study Group. Diurnal blood pressure in patients with mild‐to‐moderate hypertension treated with once‐daily benazepril hydrochloride Quality of life of patients with mild hypertension treated with captopril: a randomized double-blind placebo-controlled clinical trial. Comparative effects of 2.5 and 5 mg cilazapril versus placebo on daily blood pressure load. Valsartan, a new angiotensin II antagonist for the treatment of essential hypertension: efficacy, tolerability and safety compared to an angiotensin-converting enzyme inhibitor, lisinopril Steady‐State Pharmacokinetics and Pharmacodynamics of Cilazapril in the Presence and Absence of Cyclopenthiazide Antihypertensive Effect of Lisinopril Assessed by 24‐Hour Ambulatory Monitoring: A Double‐Blind, Placebo‐Controlled, Cross‐Over Study The Effect of Ramipril on Ambulatory Blood Pressure: A Multicenter Trial Serum lipoprotein profile under different antihypertensive therapy. The effects of benazepril, a new angiotensin‐converting enzyme inhibitor, in mild to moderate essential hypertension: A multicenter study Vasodilator effects of enalapril in patients with arterial hypertension. Twenty-four-hour ambulatory blood pressure monitoring and antihypertensive treatment: focus on ACE inhibitors. Effects of nitrendipine and enalapril on left ventricular mass in patients with non‐insulin‐dependent diabetes mellitus and hypertension Chronic dose-response curve of enalapril in essential hypertensives. An Italian multicenter study. A double-blind study to compare the efficacy, tolerance and safety of two doses of the angiotensin converting enzyme inhibitor ramipril with placebo. ACE Inhibition with Spirapril Improves Diastolic Function at Rest Independent of Vasodilation During Treatment with Spirapril in Mild to Moderate Hypertension A comparative trial of controlled-onset, extended-release verapamil, enalapril, and losartan on blood pressure and heart rate changes. Effects of benazepril and hydrochlorothiazide, given alone and in low- and high-dose combinations, on blood pressure in patients with hypertension. A new trial of the efficacy, tolerability, and safety of angiotensin-converting enzyme inhibition in mild systemic hypertension with concomitant diseases and therapies. Perindopril Therapeutic Safety Study Group (PUTS). Ambulatory blood pressure monitoring can play an integral role in patient selection, dosage adjustment and efficacy assessment in clinical trials of antihypertensive agents Superiority of home blood pressure measurements over office measurements for testing antihypertensive drugs. Captopril does not improve insulin action in essential hypertension: A double‐blind placebo‐controlled study Additive effects of diltiazem and lisinopril in the treatment of elderly patients with mild-to-moderate hypertension. Dose response and safety of telmisartan in patients with mild to moderate hypertension. A randomized, placebo-controlled, double-blind, parallel study of various doses of losartan potassium compared with enalapril maleate in patients with essential hypertension. Dose‐Response Relationship of Ramipril in Patients with Mild‐to‐Moderate Hypertension Quinapril: A Double-Blind, Placebo-Controlled Trial in Essential Hypertension ACE-inhibition with perindopril in essential hypertensive patients with concomitant diseases. The Perindopril Therapeutic Safety Collaborative Research Group. Nitrendipine and Enalapril Combination Therapy in Mild to Moderate Hypertension: Assessment of Dose-Response Relationship by a Clinical Trial of Factorial Design Treatment of patients with essential hypertension: amlodipine 5 mg/benazepril 20 mg compared with amlodipine 5 mg, benazepril 20 mg, and placebo. A double-blind randomized evaluation of converting enzyme inhibition as the first-step treatment of mild to moderate hypertension. Effective dose range of enalapril in mild to moderate essential hypertension. Effects of Perindopril on Serum Lipids in Hypertensive Patients with Hyperlipidemia Low-dose captopril for the treatment of mild to moderate hypertension. Usefulness of piretanide plus ramipril for systemic hypertension: a multicenter trial. Discrepancies between clinic and ambulatory blood pressure responses to cilazapril therapy. Lisinopril dose-response relationship in essential hypertension. Enalapril in low‐renin essential hypertension Effect of cilazapril on glucose tolerance and lipid profile in hypertensive patients with non-insulin-dependent diabetes mellitus. Increased renal plasma flow in long‐term enalapril treatment of hypertension Antihypertensive effectiveness of low-dose lisinopril-hydrochlorothiazide combination. A large multicenter study. Lisinopril-Hydrochlorothiazide Group. ACE inhibitors, beta-blockers, calcium blockers, and diuretics for the control of systolic hypertension. Placebo-controlled comparison of captopril, metoprolol, and hydrochlorothiazide therapy in non-insulin-dependent diabetic patients with primary hypertension. Fosinopril monotherapy: Relationship between blood pressure reduction and time of administration Dose-finding study of cilazapril (Inhibace) in patients with uncomplicated essential hypertension. [Antihypertensive effect of fosinopril in mild hypertension]. Cilazapril plus hydrochlorothiazide: improved efficacy without reduced safety in mild to moderate hypertension. A double-blind placebo-controlled multicenter study of factorial design.
abstract: Fourteen patients with mild to moderate essential hypertension were r and omized , after a baseline placebo period of 4 weeks , to receive the angiotensin converting enzyme ( ACE ) inhibitor quinapril or a placebo . During a 12 week , double-blind phase , the dosage of quinapril was increased from 10 to 40 mg twice daily being doubled every 4 weeks . At the end of the baseline period and of each month of the double-blind phase , 12 h overnight urine collection s were made and morning blood sample s were taken about 12 h after the last dose of medication . During the double-blind phase , blood pressure in the  quinapril  group ( n = 7 ) decreased from 159 ± 3/105 ± 1 to 141 ± 6/94 ± 2 mm Hg ( mean ± SEM ) . Serum ACE activity and plasma angiotensin II concentration were reduced to 4 ± 1 % and 14 ± 1 % of the pretreatment values , respectively . Neither the plasma concentrations nor the urinary excretions of prostagl and in E2 , 6-keto-prostagl and in F1α ( a prostacyclin metabolite ) , or thromboxane B2 ( a metabolite of thromboxane A2 ) were affected by quinapril . In the placebo group , blood pressure tended to decline but the biochemical variables remained essentially unchanged . These results indicate that prostanoids are not involved in the antihypertensive action of quinapril , the principal effect of which seems to be inhibition of the renin-angiotensin system Summary The presence of slightly increased urinary albumin excretion ( UAE ) , even at levels well below levels detectable by an ordinary dipstick , has been suggested as a predictor of cardiovascular morbidity and as a reflection of the degree of overall vascular permeability . The aim of the present investigation was to study the effects of two different antihypertensive drug regimens , an ACE inhibitor and aβ-adrenoceptor antagonist , on the low UAE rate observed in subjects with uncomplicated , mild to moderate primary hypertension . After a 4-week placebo run-in period , 49 patients ( mean age 54 y ) were r and omly assigned in a double blind manner either to further 4 weeks on placebo ( P , n = 15 ) , 8 weeks on lisinopril ( L , n = 17 ; 20 mg/40 mg o. d. ) or 8 weeks on atenolol ( A , n = 17 ; 50 mg/100 mg o. d. ) . The 24-h UAE was measured every second week . At entry and after 4 weeks the glomerular filtration rate and the renal plasma flow were measured . Both drugs lowered blood pressure ( BP ) to a similar extent after 4 and 8 weeks of treatment ; the blood pressures were 160/106 ( P ) , 159/104 ( L ) and 154/103 ( A ) at entry , and 133/83 ( L ) and 134/87 ( A ) at the end of the study after 8 weeks . On entry the 24-h UAE in all patients ranged from 4 to 49 mg ( mean 14.1 mg ) , and it did not differ significantly between groups . After 4 weeks the UAE during 24 h was reduced by approximately one third in the lisinopril-treated group , and by 10 % in the atenolol reated group , whereas it remained unaltered in the group on placebo . After 8 weeks the 24-hour UAE was approximately 20 % lower compared to baseline levels in the lisinopril-treated patients . In the atenolol-treated group the UAE was unaltered compared to baseline . However , none of the changes in the UAE was statistically significant , nor were there any statistically significant differences between the two antihypertensive regimens . Moreover , there were no significant effect of the lisinopril or atenolol  treatment on renal function or on renal haemodynamics . It is concluded that in patients with uncomplicated , mild to moderate hypertension both an ACE-inhibitor , such as lisinopril , as well as aβ1-selective adrenoceptor blocking agent , such as In a double-blind , parallel-group study , 260 patients with mild to severe essential hypertension were r and omized to treatment with placebo or spirapril at 6 , 12 or 24 mg once daily for 6 weeks . When blood pressures were measured at the end of the dosing interval ( trough ) , all spirapril regimens had produced similar reductions in sitting systolic and diastolic blood pressures ( siSBP/siDBP ) which were significantly greater than those observed in placebo-treated patients . There were no relevant changes in resting heart rate in any of the study groups . At the study endpoint , the mean reductions in siSBP/siDBP were 14.9/11.5 mmHg with spirapril at 6 mg , 15.4/12.0 mmHg with spirapril at 12 mg and 17.8/12.4 mmHg with spirapril at 24 mg/day vs. 3.1/3.6 mmHg with placebo . In a subgroup of 122 patients , blood pressure was recorded at the end of the dosing interval and during the 8 hours immediately postdose to monitor the peak effects on blood pressure . All spirapril dosages produced similar reductions at peak with a mean decrease of siDBP of approximately 20 mmHg in comparison to baseline values vs 6 - 7 mmHg with placebo . The trough : peak ratios for 6 , 12 and 24 mg all lay between 60 % and 90 % for siSBP and siDBP , indicating that most of the peak effect was maintained at trough . Spirapril was well tolerated ; the adverse event profile was not different from that with placebo , and no dose-related adverse events were observed . ( ABSTRACT TRUNCATED AT 250 WORDS Dry cough is a troublesome side-effect associated with certain antihypertensive agents that act by modulating aspects of the renin-angiotensin-aldosterone system . The incidence of dry cough associated with two of these therapies , the novel All receptor antagonist telmisartan and the ACE inhibitor lisinopril , was assessed in a multicentre , r and omised , parallel-group , double-blind , placebo-controlled , 8-week study of 88 patients with mild to moderate hypertension who previously demonstrated ACE inhibitor-related cough . Patients received either telmisartan 80 mg , lisinopril 20 mg , or placebo once daily . Cough incidence , measured at each visit by a self-administered symptom assessment question naire , was significantly higher with lisinopril ( 60 % ) than with telmisartan ( 15.6 % ) or placebo ( 9.7 % ) . A visual analogue scale demonstrated a similar trend for cough frequency . Thus the incidence of cough with telmisartan 80 mg is significantly less than that seen with lisinopril 20 mg and is comparable to placebo 1 . We describe an approach involving a smaller , shorter study , leading onto a longer , larger study in which the antihypertensive effects of ascending doses of imidapril , a new ACE inhibitor , were investigated . Both studies were planned prospect ively , assuming a clinical ly useful fall in BP to be 8 mm Hg ( s.d . = 9 ) . The studies included patients with mild to moderate essential hypertension ( baseline sitting diastolic blood pressure ( SDBP ) 95 - 115 mm Hg ) . After a placebo run-in of 2 - 3 weeks patients received either placebo or imidapril 2.5 , 5 , 10 or 20 mg in the 2 week study ( n = 91 ) or imidapril 5 , 10 , 20 or 40 mg in the 4 week study ( n = 162 ) . 2 . The overall mean baseline SDBP was 103.4 mm Hg ( s.d . 0.62 ) in the initial study and 101.5 mm Hg ( s.d . 0.41 ) in the 4 week study . 3 . Compared with placebo , imidapril 10 , 20 and 40 mg significantly reduced SDBP . There was no significant difference between these doses , suggesting that 10 mg achieved maximal ACE inhibition in most patients . The 2.5 mg dose showed no significant effect . The 5 mg dose gave an intermediate effect . In both studies the overall incidence of adverse events was similar in the imidapril and placebo groups , and was not worrying In a double-blind , r and omized , cross-over , placebo- and rest-period controlled study with two 4-week treatment periods , we examined the effects of angiotensin converting enzyme ( ACE ) inhibition with fosinopril ( 20 mg/day ) on the postexercise  pressor and forearm vasoconstrictor responses to a 60 sec cold pressor test . The results indicate that pressor and vasoconstrictor responses were unaffected by prior exercise , fosinopril , and both interventions combined . Expression of the responses as percent change from baseline levels provided identical results indicating that changes in baseline values did not mask an altered vascular responsiveness . It is concluded that skeletal muscle vascular responsiveness to sympathetic nervous activity is unchanged after exercise or during ACE inhibition with fosinopril Co-administration of antihypertensive drug therapy and hormonal replacement therapy ( HRT ) is frequent in postmenopausal women but it is not known whether HRT interacts with concomitant antihypertensive therapy . The present study was design ed to investigate efficacy and safety of the ACE inhibitor moexipril in comparison to placebo in hypertensive , postmenopausal women on HRT . After a 4-week placebo run-in phase , 95 postmenopausal women ( 35–74 years of age ) who had a sitting diastolic blood pressure ( BP ) of 95–114 mm Hg and were treated with HRT were r and omised to a 12-week treatment with moexipril 15 mg or placebo .  Efficacy and safety were assessed by measuring changes in sitting BP and metabolic parameters associated with cardiovascular disease including triglycerides , total cholesterol , HDL , LDL , total cholesterol/HDL ratio and glucose . Adverse events were recorded continuously . After 12 weeks of treatment , moexipril 15 mg was significantly more effective in reducing sitting systolic and diastolic BP from baseline than placebo ( −12.2/ −9.9 mm Hg vs −1.6/−4.3 mm Hg , P < 0.001 ) . metabolic parameters were not affected by treatment with moexipril  : mean levels of triglycerides , total cholesterol , hdl , ldl , total cholesterol/hdl ratio and glucose remained unchanged throughout the study . fibrinogen , an independent cardiovascular risk factor , increased after placebo ( + 35.0 mg/dl ) and decreased after treatment with moexipril ( −33.6 mg/dl ) , the difference , however , was not statistically significant .  moexipril  was well-tolerated by postmenopausal women using hrt . the most frequent adverse events included headache ( 21.3 % ) , cough ( 12.8 % ) and rhinitis ( 10.6 % ) and there were no significant differences in the number and severity of adverse events between the moexipril and placebo groups . this study indicates that moexipril is effective and well tolerated in the treatment of hypertensive , postmenopausal women and can safely be co-administered to hrt Cilazapril ( CLZ ) is a new , long-acting nonsulfhydril converting enzyme inhibitor ( ACE-I ) . Its effect on peak and trough sitting diastolic blood pressure ( SDBP ) was studied in a total of 85 patients with uncomplicated , essential hypertension at three centers . After 4 weeks of a single-blind placebo ( PLA ) run-in period , patients whose SDBP was between 100 and 115 mm Hg , were r and omized into active treatment with either PLA ( n = 27 ) , CLZ 2.5 mg ( n = 29 ) , or CLZ 5 mg ( n = 29 ) once daily in a double-blind fashion for another 8 weeks . At the end of the PLA run-in and after 4 and 8 weeks active therapy , an hourly blood pressure ( BP ) profile during 1–10 and 21–24 h postdose was performed . The drop in SDBP at the end of the active treatment period at peak and trough was statistically and clinical ly significant for both CLZ doses in comparison with the PLA group . The peak/trough ratio after substraction of the PLA effect was 62 % for CLZ 2.5 mg and 59 % for CLZ 5 mg . These results indicate that the dose regimen of CLZ 2.5–5 mg once daily is adequate and effective for 24 Two hundred and eleven patients with mild or moderate hypertension , mean age 53.5 + /- 9.5 years ( range 24 - 70 ) were r and omised double-blind to treatment with either captopril 50 mg ( C50 ) , hydrochlorothiazide 25 mg ( HCTZ 25 ) , the fixed combination of captopril 50 mg and hydrochlorothiazide 25 mg ( C50/HCTZ 25 ) or placebo .  Blood pressure , heart rate , body weight and side effects were assessed at the end of the run-in period on placebo and after 4 , 6 , 8 weeks treatment at the same time , 20 - 24 h after the last dosing . Routine biochemical examinations were carried out on all patients after the placebo period as well as after 4 and 8 weeks . Blood pressure significantly decreased in all groups , but the mean percentage change from baseline was highly statistically significant at 8 weeks , for C50 and C50/HCTZ 25 groups . The incidence of clinical side effects was low and not statistically different for the four groups with few specific adverse effects ( one transient alteration of taste in captopril group ) . No patient was withdrawn from the study due to side effects . A better anti-hypertensive efficacy was obtained with the fixed combination captopril 50 mg/hydrochlorothiazide 25 mg once daily compared to placebo or each component alone , and without any difference in side effects AIMS To assess the effect of tr and olapril ( 2 mg once daily ) and indomethacin ( 25 mg three times daily ) , alone and in combination , on renal function and renal functional reserve in hypertensive patients ( DBP 95 - 115 mmHg ) requiring regular non-steroidal anti-inflammatory drugs ( NSAIDs ) . METHODS R and omized , double-blind , placebo-controlled , four way crossover design . After 3 weeks treatment renal plasma flow ( RPF ) and glomerular filtration rate ( GFR ) were measured using the p-aminohippurate ( PAH ) and inulin methods . Renal functional reserve was estimated by measuring RPF and GFR at the end of an intravenous infusion of dopamine 2 microg kg(-1 ) and 10 % amino acid solution . RESULTS There was no significant difference in RPF between treatments : -22.79 ml min(-1 ) ( 95 % CI -54.82 , 9.24 ) for placebo and tr and olapril , -10.37 ml min(-1 ) ( 95 % CI -30.7 , 9.96 ) for placebo and indomethacin , -14.78 ml min(-1 ) ( 95 % CI -50.33 , 20.77 ) for placebo and tr and olapril with indomethacin . There was no significant difference in functional reserve RPF between treatments : -34.96 ml min(-1 ) ( 95 % CI -119.8 , 49.88 ) for placebo and tr and olapril , 29.78 ml min(-1 ) , -15.18 , 74.74 ) for placebo and indomethacin , and -25.84 ml min(-1 ) ( 95 % CI -87.62 , 35.94 ) for placebo and tr and olapril with indomethacin . There was no significant difference in GFR between treatments : -1.01 ml min(-1 ) ( 95 % CI -7.45 , 5.42 ) for placebo and tr and olapril , -7.88 ml min(-1 ) ( 95 % CI -15.08 , -0.68 ) for placebo and indomethacin , and -0.36 ml min(-1 ) ( 95 % CI -7.58 , 6.86 ) for placebo and tr and olapril with indomethacin . There was no significant difference in functional reserve GFR between treatments : 5.13 ml min(-1 ) ( 95 % CI -4.97 , 15.23 ) for placebo and tr and olapril , 6.31 ml min(-1 ) ( 95 % CI -1.88 , 14.5 ) for placebo and indomethacin , 7.21 ml min(-1 ) ( 95 % CI 1.26 , 13.16 ) for placebo and tr and olapril with indomethacin . CONCLUSION In hypertensives chronic treatment with NSAIDs or ACEI alone or in combination did not change RPF or GFR and did not change renal functional reserve capacity of RPF or GFR The efficacy of once-a-day cilazapril ( a new long acting converting enzyme inhibitor ) therapy for the 24 h control of hypertension and its effects on the renin-angiotensin axis were investigated . Twenty-four uncomplicated hypertensive patients whose sitting diastolic blood pressures remained within 94 to 114 mmHg after four weeks of placebo were r and omly assigned on a double-blind basis to receive either continued placebo or cilazapril therapy at a single dose of 1.25 , 2.5 or 5.0 mg/day for a further four weeks . At the end of weeks 4 and 8 , systolic and diastolic blood pressures and heart rates were recorded , supine and st and ing , at 0 , 2 , 4 , 6 , 9 , 12 and 24 h following a single dose of drug . At the same times , blood was withdrawn for determination of plasma renin activity and aldosterone . Supine and erect systolic and diastolic blood pressures were lowered to normotensive levels with an optimal response being achieved at a dose of 2.5 mg/day . Supine and erect heart rates were unchanged with respect to drug dosage , and the reflex increase in heart rate and diastolic blood pressure on changing from supine to erect posture was maintained in all groups . Maximum antihypertensive efficacy was from 2 to 6 h after drug ingestion . There were no changes in resting aldosterone , but plasma renin activity was increased at all drug dosages . A single 2.5 mg dose of cilazapril provides blood pressure control for a 24 h period . Cilazapril does not appear to interfere with the reflex autonomic responses to postural change Summary The aim of the study was to evaluate whether the combination of ketanserin with captopril exerts an additive antihypertensive effect , as compared with single drug treatment . Twelve patients with uncomplicated moderate essential hypertension received , according to a r and omized , double-blind , crossover design , ketanserin ( 40 mg twice daily ) , captopril ( 50 mg twice daily ) , the combination of the two drugs at these dosages , and the corresponding placebo , each treatment being given for 1 month . Both ketanserin and captopril as monotherapy similarly and significantly reduced blood pressure as compared with placebo ( p<0.001 ) . The combination treatment of ketanserin plus captopril further and significantly reduced blood pressure when compared with single drug treatment ( p<0.001 ) . Moreover , the percentage of responders and patients whose blood pressure was normalized were significantly greater under the combined treatment than under ketanserin or captopril monotherpy ( p<0.001 ) . These data indicate that the combination of ketanserin plus captopril exerts a clear additive antihypertensive effect when compared with each treatment as monotherapy , a finding that suggests this combination can be usefully employed in the treatment of hpertensive patients Perindopril erbumine , a new long‐acting , non‐sulfhydryl‐containing angiotensin converting enzyme inhibitor , was evaluated in 289 patients with hypertension in a 16‐week , double‐blind , placebo‐controlled dose‐ranging study . After 4 weeks of single‐blind placebo treatment , patients with supine diastolic arterial pressures from 95 to 114 mm Hg were r and omized to receive placebo , 4 mg perindopril once daily , or 2 mg perindopril twice daily . The daily dose of perindopril was increased by 4 mg every 4 weeks to a maximum of 16 mg per day . Mean decreases in systolic and diastolic arterial pressure were greater with perindopril than with placebo ( p < 0.05 ) . The dose‐response curve flattened after 8 mg per day , and there was no difference in arterial pressure reduction or in the percentage of responders between once‐ and twice‐daily administration of perindopril . Adverse reactions with perindopril were generally mild and , with the exception of cough , were similar with placebo . The findings of this study indicate that perindopril is effective , well tolerated , and suitable for once‐daily administration for the treatment of hypertension We compared the effects of angiotensin-converting enzyme inhibition with quinapril to those of selective beta-blockade with atenolol and calcium channel blockade with verapamil in 10 hypertensive subjects in a r and omized double-blind placebo-controlled crossover study . All antihypertensive agents reduced baseline mean arterial pressure equally and did not modify forearm vascular resistance compared to placebo . In response to sustained h and grip exercise , both quinapril and verapamil , but not atenolol , attenuated the pressor response . However , verapamil was associated with an exaggerated increase in forearm vascular resistance during h and grip , whereas quinapril did not alter this response compared to placebo . It is concluded that quinapril and verapamil reduce the pressor response during isometric exercise by quantitatively different effects on the vasoconstrictor response in , as well as outside of , skeletal muscles Clinical studies indicate that the angiotensin-converting enzyme inhibitor quinapril is an effective antihypertensive agent when administered once daily . At the end of a 4-week , double-blind crossover trial comparing quinapril and placebo , patients were admitted for a hemodynamic profile study 12 hours after taking the previous dose . A final 20 mg dose of quinapril had no additional effect on blood pressure . This is interesting inasmuch as the plasma half-life of the active metabolite quinaprilat is approximately 2 hours and the effective accumulation half-life is approximately 3 hours . The blood pressure reduction in patients with mild hypertension receiving long-term quinapril therapy may be more closely related to prolonged angiotensin-converting enzyme inhibition or to an effect on tissue angiotensin II concentration than to the plasma half-life . This may be the case particularly for cardiac output and renal circulation , because quinapril lowers total vascular resistance without increasing cardiac output or disturbing autoregulation of renal blood flow . Reduced ventricular wall stress , improved diastolic function , and lower renal perfusion pressure may spare cardiac function and glomeruli from hypertensive vascular damage 1 . The antihypertensive efficacy and tolerability of a low dose combination of the angiotensin converting enzyme inhibitor ramipril ( 2.5 mg ) and the extended release formulation of the dihydropyridine calcium channel antagonist felodipine ( 5 mg ) were assessed in a double-blind , double dummy placebo controlled , r and omised , crossover study in 20 patients ( mean age 55.4 years ; range 46 - 69 ) with uncomplicated mild to moderate hypertension ( supine diastolic > 90 mmHg < 115 mmHg after 4 weeks of single-blind wash-out on placebo ) . The four r and omised , double-blind , crossover study phases evaluated the response to 4 weeks of once daily treatment with placebo , monotherapy with each drug and the combination .  Noninvasive ambulatory blood pressure monitoring ( Spacelabs 90207 ) was performed for 24 h at the end of each phase . 2 . The mean 24 h ambulatory blood pressure ( mmHg ) was 147.9/92.0 following placebo , 141.3/87.8 following monotherapy with ramipril 2.5 mg , 136.8/85.8 following monotherapy with felodipine ER 5 mg and 131.1/82.6 following the combination of ramipril 2.5 mg and felodipine ER 5 mg . All active treatment phases significantly reduced mean 24 h ambulatory diastolic pressure by comparison with placebo . The antihypertensive efficacy of the combination was additive . 3 . The coadministration of ramipril did not attenuate the incidence of headache attributable to felodipine ER The purpose of the present study was to examine the effects of salt-restriction alone and in combination with an angiotensin-converting enzyme ( ACE ) inhibitor ( cilazapril ) on both office and ambulatory blood pressure ( BP ) levels in free living subjects with elevated BP . The study was carried out in an out-patient setting with subjects recruited from occupational health care system mainly . After exclusions , 39 subjects ( 24 men , 15 women , aged 28 - 65 years ) with mildly to moderately elevated BP completed the study . After 3 months run-in period with placebo ( first month on normal-salt and the next 2 months on sodium-restricted diet ) the subjects were r and omised into either salt-restriction placebo or salt-restriction cilazapril ( 2.5 mg daily ) groups for 3 months . In the whole group , 24-h urinary sodium excretion decreased ( mean + /- s.d . ) from 198 + /- 60 to 112 + /- 59 mmol ( 4 weeks vs 24 weeks , P < 0.001 ) . Systolic and diastolic office BP decreased during the placebo-sodium-restriction phase ( -7.1 [ 95 % Cl -11.2 ; -3.0 ] and -4.2 [ 95 % Cl -6.6 ; -1.8 ] mm Hg for systolic and diastolic BP ) , and similarly the daytime ambulatory BP ( ABP ) was reduced during this period ( -2.8 [ 95 % Cl -5.2 ; -0.5 ] and -2.8 [ 95 % Cl -4.5 ; -1.2 ] mm Hg , systolic ( SBP ) and diastolic blood pressure ( DBP ) respectively ) . No changes were observed in the night time ABP . Addition of cilazapril to sodium-restriction enhanced significantly the office BP ( -13.2 , [ 95 % Cl -20.2 ; -6.2 ] , and -9.1 [ 95 % Cl -13.5 ; -4.7 ] ) and daytime ABP ( -5.9 , [ 95 % Cl -10.1 ; -1.8 ] and -5.3 , [ 95 % Cl -8.8 ; -1.9 ] ) reduction . Blood glucose , plasma insulin or serum lipids did not change during the study . Moderate sodium restriction seems to lower the office and daytime ABP levels in subjects with mild-to-moderate hypertension . The antihypertensive effect of cilazapril could be enhanced by sodium restriction Objective To compare the antihypertensive efficacy and systemic tolerability of valsartan , a new angiotensin II receptor antagonist , with placebo and with an angiotensin converting enzyme ( ACE ) inhibitor , enalapril . Design A total of 348 adult out patients with mild-to-moderate uncomplicated essential hypertension participated in this double-blind , parallel , study . Patients were allocated r and omly in a ratio of 2:2:1 to receive 80 mg valsartan once a day , 20 mg enalapril once a day , or placebo for 8 weeks in general practice . Patients were assessed at 4 and 8 weeks of therapy . Main outcome measures The primary efficacy variable was the change from baseline in mean sitting diastolic blood pressure ( SDBP ) after 8 weeks of therapy . Secondary variables included the change in sitting systolic blood pressure ( SSBP ) and response rates at 8 weeks . Results Valsartan and enalapril produced statistically significant reductions in diastolic and systolic blood pressures compared with placebo . Similar falls were found in both of the active treatment groups with mean changes in SDBP at 8 weeks of — 9.5mmHg for valsartan and — 9.4mmHg for enalapril ( 4.5mmHg for placebo ) . No significant differences between valsartan and enalapril were found for reductions in SDBP or SSBP . Response rates at 8 weeks were significantly greater for valsartan ( 54 % ) and enalapril ( 58 % ) than for placebo ( 20 % ) , with no significant difference between the two active treatments . Both valsartan and enalapril demonstrated a consistent a nti hypertensive effect over time , with 90 % of patients with a response at 4 weeks responding at 8 weeks . Both of the treatments were tolerated well . Although the incidence of coughing was generally low in the study , more cases were reported with enalapril ( three ) than with valsartan ( one ) or placebo ( none ) . Conclusions The data show 80 mg valsartan once a day to be as effective as 20 mg enalapril once a day in the treatment of mild-to-moderate hypertension . Valsartan is tolerated well and does not appear to be associated with any increase in the incidence of coughing In order to evaluate the antihypertensive effect and the tolerability of combination therapy with an angiotensin converting enzyme inhibitor ( captopril ) and a dihydropyridine calcium antagonist ( nifedipine ) compared with monotherapy and placebo , we studied 32 uncomplicated essential hypertensives . At the end of a 1-month placebo washout period , their diastolic blood pressure was > 105 and < 120mmHg . The subjects then received , according to a double-blind r and omized crossover design , captopril ( 50 mg twice daily ) , nifedipine ( 20 mg twice daily ) , captopril plus nifedipine at the same doses and the corresponding placebo , each treatment being given for 1 month . Both captopril and nifedipine significantly reduced mean blood pressure , which was further and significantly reduced by the combination of the two drugs . The decreases in mean blood pressure induced by nifedipine were significantly greater than those induced by captopril , and those induced by the combined therapy were significantly greater than those induced by either drug on monotherapy . The heart rate was significantly increased only by nifedipine , and to a similar , but not significant , extent by the combination therapy . Plasma renin activity was similarly and significantly increased and urinary aldosterone tended to decrease to a similar extent under the three active treatments . Adverse effects were mild to moderate in intensity ; their incidence under captopril was lower than that under placebo , while the incidence under nifedipine and combined therapy was greater than under placebo .  Ankle oedema disappeared under the combined therapy in three out of four patients who developed this side effect under nifedipine , although one additional patient developed ankle oedema under combination therapy . These data indicate that : ( 1 ) captopril and nifedipine are effective antihypertensive drugs with a balanced cost-benefit ratio , since even if nifedipine alone was more effective in reducing blood pressure , it was less well tolerated than captopril ; ( 2 ) the combination of captopril and nifedipine exerted an additive antihypertensive effect without aggravating , and possibly even reducing , the incidence of adverse effects due to nifedipine . These findings confirm that the association of an angiotensin converting enzyme inhibitor with a dihydropyridine calcium antagonist can be useful in the treatment of essential hypertension The immediate ( 0 to 24 hours ) and long-term ( 4 weeks ) hypotensive effects of a new long-acting angiotensin converting enzyme inhibitor , ramipril ( HOE 498 ) , as well as adverse effects and tolerance , were evaluated in 34 patients with primary hypertension . Further , effects on serum and urinary aldosterone and circulating angiotensin II concentrations were measured . After short- and long-term administration of 5 or 10 mg of ramipril , the mean blood pressure was significantly lowered compared with placebo . The mean maximum decrease in blood pressure was noted 4 to 8 hours after administration of ramipril once daily . Sustained blood pressure reduction was achieved after 4 weeks of treatment . Serum concentrations of aldosterone and plasma levels of circulating angiotensin II were reduced for up to 12 hours after drug intake , and tended to return to pretreatment levels at 24 hours . Serum angiotensin converting enzyme activity was markedly suppressed for more than 24 hours after a single dose of 5 or 10 mg ramipril . No subjective or objective adverse effects were noted , and the tolerance to the drug was very good Objective To identify appropriate dosages of ramipril and hydrochlorothiazide ( HCT ) when given in combination once a day for the treatment of essential hypertension . Design A 2- or 4-week placebo run-in followed by 6-week , double-blind , parallel-group phase : 4 x 3 factorial ( 2.5 , 5 and 10 mg ramipril ; 12.5 and 25 mg HCT ; all six combinations ; placebo ) . Setting Office practice ( 21 centres ) . Patients and participants Patients with mild-to-moderate essential hypertension ( World Health Organization stage I — II ; supine diastolic blood pressure 100—115 mmHg in last 2 weeks of run-in ) : 581 enrolled , 534 r and omly assigned to double-blind therapy and 517 completed . Main outcome measures Reduction in supine and st and ing blood pressure . Results In pairwise comparisons , the combinations of 5 mg ramipril with 12.5 and 25 mg HCT and 10 mg ramipril with 12.5 mg HCT consistently produced significantly greater blood pressure reductions than their respective components . Response surface analyses were performed , and a stairstep model was constructed to characterize the shape of the dose-response surface . The combinations involving 5 and 10 mg ramipril with 12.5 and 25 mg HCT were again more effective than their components . Withdrawals and adverse effects were minimal for all treatments . A large drop in serum potassium was observed on 25 mg HCT , but not on combination therapy . Addition of ramipril appeared to reduce the hyperuricaemic effect of HCT . Conclusions Several dosage combinations of ramipril plus HCT produced significantly greater blood pressure reductions than the monotherapies at the same dosages . Overall , the combination of 5 mg ramipril and 25 mg HCT gave the best mean reduction . Combination therapy with ramipril plus HCT was safe and effective for patients with mild-to-moderate essential hypertension The combination of angiotensin converting enzyme ( ACE ) inhibitor and thiazide diuretic has advantages over monotherapy for the treatment of hypertension . Previous study design s have often been inadequate to demonstrate the details of interactions between these antihypertensive agents . This study used a modified 4 x 4 factorial r and omized , double-blind , placebo-controlled , parallel group design to study the efficacy of 17 different doses of fosinopril ( Fos ) , a phosphinic acid derived ACE inhibitor , and hydrochlorothiazide ( HCTZ ) in 550 patients with mild to moderate hypertension . Data from these variables were fit to quadratic response surface models ( QRSM ) using polynomial functions in the doses of the two components . Using QRSM , seated systolic ( SeSBP ) and diastolic blood pressure ( SeDBP ) responses at 8 weeks were predicted for actual doses and interpolated for intermediate doses not studied . Fos and HCTZ alone and in combination produced a dose-related reduction in SeSBP and SeDBP . Using 10 mg Fos + 12.5 mg HCTZ reduced the adjusted mean SeDBP 6.3 mm Hg and 20 mg Fos + 12.5 mg HCTZ lowered the same measure 9.1 mm Hg . Coadministration of Fos and HCTZ produced an additive antihypertensive effect . This study of combination agents for hypertension using a factorial design with QRSM accurately predicts dose responses and is a valuable clinical trial methodology Objective : To compare the efficacy , tolerability , and safety of once-daily therapy with amlodipine 5 mg/benazepril 10 mg vs amlodipine 5 mg , benazepril 10 mg , and placebo . Design : R and omised , double-blind , placebo-controlled , parallel-group , multicentre trial . Setting : Twenty-two clinical centres , including private practice groups and academic research clinics . Patients : A total of 530 patients between 21 and 80 years of age with essential hypertension were screened for the study , and 454 were r and omised to treatment with amlodipine 5 mg/benazepril 10 mg , amlodipine 5 mg , benazepril 10 mg , or placebo for 8 weeks . Results : Amlodipine 5 mg/benazepril 10 mg produced greater reductions from baseline in sitting diastolic blood pressure than amlodipine 5 mg ( P < 0.03 ) , benazepril 10 mg ( P < 0.001 ) , and placebo ( P < 0.001 ) . The response rate in the amlodipine 5-mg/benazepril 10-mg treatment group ( 66.4 % ) was better than that observed in the amlodipine 5-mg ( 50.0 % P < 0.02 ) , benazepril 10-mg ( 38.3 % P < 0.001 ) , and placebo ( 24.4 % P < 0.001 ) groups . There was no significant difference in heart rate among the four groups . The incidence of oedema in the amlodipine 5-mg/benazepril 10-mg ( 1.7 % ) group was somewhat less than that in the amlodipine 5-mg ( 4.5 % ) group . Conclusions : Therapy with amlodipine 5 mg/benazepril 10 mg was well tolerated and was superior to amlodipine 5 mg , benazepril 10 mg , and placebo in reducing sitting diastolic blood pressure in patients with essential hypertension OBJECTIVE A double-blind , placebo-controlled multicenter study involving 34 centers from different Brazilian regions was performed to evaluate the antihypertensive efficacy and tolerability of tr and olapril , an angiotensin I converting enzyme inhibitor , in the treatment of mild-to-moderate systemic arterial hypertension . METHODS Of 262 patients enrolled in this study , 127 were treated with tr and olapril 2 mg/day for 8 consecutive weeks , and the remaining 135 patients received placebo  for the same period of time . Reduction in blood pressure ( BP ) and the occurrence of adverse events during this period were evaluated in both groups . RESULTS Significantly reductions in both systolic and diastolic pressures were observed in patients treated with tr and olapril when compared with those on placebo .  Antihypertensive efficacy was achieved in 57.5 % of the patients on tr and olapril and in 42 % of these normal values of BP were obtained . The efficacy of tr and olapril was similar in all centers , regardless of the area of the country . In a subset of 30 patients who underwent ABPM , responders showed a significant hypotensive effect to tr and olapril throughout the 24 hour day . The adverse event profile was similar in both tr and olapril and placebo groups . CONCLUSION Our results demonstrate , for the first time in a large group of hypertensive patients from different regions in Brazil , good efficacy and tolerability of tr and o-lapril during treatment of mild-to-moderate essential systemic hypertension This multicenter , placebo-controlled , double-blind trial of factorial design evaluated the safety and efficacy of combination treatment with the angiotensin-converting enzyme inhibitor , enalapril , and the vascular selective calcium antagonist felodipine extended release ( ER ) in patients with essential hypertension . After a 4-week , single-blind placebo baseline period , 707 patients with sitting diastolic blood pressures ( BPs ) in the range of 95 to 115 mm Hg received placebo , enalapril ( 5 or 20 mg ) , felodipine ER ( 2.5 , 5 , or 10 mg ) , or their combinations for an 8-week double-blind treatment period . All doses of enalapril and felodipine ER had a statistically significant ( p < 0.05 ) additive effect in reducing both systolic and diastolic BP . The trough to peak ratios for the combinations ranged from 0.63 ( enalapril 5 mg-felodipine ER 2.5 mg ) to 0.79 ( enalapril 20 mg-felodipine ER 10 mg ) and were consistent with effective BP control with 1 dose/day . Patients aged > or = 65 years demonstrated a greater reduction in diastolic BP . Combinations of enalapril-felodipine ER were associated with less drug-induced peripheral edema ( 4.1 % ) compared to felodipine ER monotherapy ( 10.8 % ) . There were no serious drug-related adverse effects observed during the study . In this trial , the combination of enalapril and felodipine ER effectively lowered BP and was generally well tolerated with an excellent safety profile when used in the treatment of hypertension Because obesity-associated hypertension has unique hemodynamic and hormonal profiles , certain classes of antihypertensive agents may be more effective than others as monotherapy . Thus , we compared the efficacy and safety of the angiotensin-converting enzyme inhibitor lisinopril and the diuretic hydrochlorothiazide in a 12-week , multicenter , double-blind trial in 232 obese patients with hypertension . Patients with an office diastolic pressure between 90 and 109 mm Hg were r and omized to treatment with daily doses of lisinopril ( 10 , 20 , or 40 mg ) ,  hydrochlorothiazide  ( 12.5 , 25 , or 50 mg ) , or  placebo . Mean body mass indexes were similar for all patients . At week 12 , lisinopril and hydrochlorothiazide effectively lowered office diastolic ( -8.3 and -7.7 versus -3.3 mm Hg , respectively ; P<.005 ) and systolic ( -9.2 and -10.0 versus -4.6 mm Hg , respectively ; P<.05 ) pressures compared with placebo .  Ambulatory blood pressure monitoring confirmed that lisinopril and hydrochlorothiazide effectively lowered 24-hour blood pressure compared with placebo ( P<.001 ) . Significant dose-response differences were observed between treatments . Sixty percent of patients treated with lisinopril had an office diastolic pressure < 90 mm Hg compared with 43 % of patients treated with hydrochlorothiazide ( P<.05 ) . Responses to therapies differed with both race and age . Neither treatment significantly affected insulin or lipid profiles ; however , plasma glucose increased significantly after 12 weeks of hydrochlorothiazide therapy compared with lisinopril ( + 0.31 versus -0.21 mmol/L ; P<.001 ) . Hydrochlorothiazide also decreased serum potassium levels by 0.4 mmol/L from baseline . In conclusion , lisinopril was as effective as hydrochlorothiazide in treating obese patients with hypertension . Treatment with angiotensin-converting enzyme inhibitors may show greater efficacy as monotherapy at lower doses compared with thiazide diuretics , may have a more rapid rate of response , and may offer advantages in patients at high risk of metabolic disorders The effects of inhibiting angiotensin converting enzyme with perindopril and aldosterone with spironolactone were tested in hypertensive patients over fifty . Accordingly , 75 patients with mild hypertension aged 50 to 70 were r and omly divided into three groups for a double-blind 8 week comparison of the actions of placebo , 4 to 8 mg/day perindopril , and 37.5 to 75 mg/day spironolactone .  Side-effects caused one patient to withdraw from placebo and one from spironolactone treatment . Mean blood pressure rose by 2.4 mm Hg after placebo but dropped by 7.4 and 8.6 after perindopril and spironolactone ( P less than .01 ) . Placebo , perindopril , and spironolactone did not alter blood glucose or plasma potassium , but induced , respectively , variations of -0.09 , 0 , and + 0.34 mmol/L in cholesterol ( P = .04 ) , and -0.02 , -0.05 , and + 0.27 mmol/L in triglycerides ( P less than .01 ) . After the three treatments , changes in angiotensin converting enzyme activity averaged -1 , -6 , and -1 mU/mL ( P less than .01 ) , in active renin -2 , + 18 , and + 28 pg/mL ( P less than .01 ) , and in aldosterone , + 15 , + 8 , and + 95 pg/mL ( P less than .01 ) . Placebo , perindopril , and spironolactone did not alter microalbuminuria , but reduced urinary kallikrein activity by 0.9 , 1.8 , and 5.4 mU/mmol creatinine ( P = .04 ) . Although short-term administration of spironolactone  raised renin and aldosterone markedly and lipids moderately ( possibly because of volume contraction ) , the present results show that perindopril and spironolactone are both safe and effective for treating hypertension at the age of 50 or older This is a r and omised , double-blind , placebo-controlled , four-way crossover study to determine if indomethacin attenuates the hypotensive effect of tr and olapril .  Twenty-three hypertensive patients ( diastolic blood pressure ( DBP ) 95 - 115 ) requiring NSAID were recruited . Seventeen completed the study . Three week treatment periods : tr and olapril 2 mg od and indomethacin 25 mg tds , tr and olapril 2 mg and placebo , indomethacin and placebo , placebo and placebo .  Clinic and ambulatory BP after 3 weeks of each treatment . Study had 85 % power to detect a 5 mm Hg difference in BP ( s.d . 7 mm Hg ) . End of treatment clinic BPs were : 152.9/98 mm Hg ( 95 % CI 147.2 , 158.6/95.8 , 101.4 ) with placebo and placebo ; 150.4/94.9 mm Hg ( 95 % CI 144.7 , 156.1/92.1 , 97.7 ) with tr and olapril and indomethacin ; 148.2/96.5 mm Hg ( 95 % CI 142.5 , 153.9/93.7 , 99.3 ) with tr and olapril and placebo ; and 156.6/97.4 mm Hg ( 95 % CI 150.9 , 162.3/94.6 , 100.2 ) with indomethacin and placebo . There were no significant interactions between tr and olapril and indomethacin for clinic systolic BP ( SBP ) ( P = 0.79 ) or clinic DBP ( P = 0.87 ) . When tr and olapril treatments ( placebo or with indomethacin ) were compared to treatments without tr and olapril ( placebo or indomethacin ) , tr and olapril lowered clinic SBP by 5.4 mm Hg ( P = 0.047 ) and DBP by 2.3 mm Hg ( P = 0.08 ) . Mean ambulatory BP was : 140.6/88.2 mm Hg ( tr and olapril and placebo ) ; 142.8/89.7 mm Hg ( tr and olapril and indomethacin ) ; 149.6/95.0 mm Hg , ( indomethacin and placebo ) ; 147.7/94.0 mm Hg ( placebo and placebo ) . Compared with placebo , tr and olapril and placebo lowered BP by 6.5/7.5 mm Hg ( P < 0.001 , SBP ; P < 0.001 , DBP ) . Compared with indomethacin , tr and olapril and indomethacin lowered BP by 5.0/5.5 mm Hg ( P = 0.001 , SBP ; P < 0.001 , DBP ) . In the present study tr and olapril 2 mg lowered clinic SBP and ambulatory BP , but indomethacin did not attenuate this . Indomethacin had no significant effect on either clinic or ambulatory BP . The antihypertensive effects of tr and olapril in this study were modest . Patient selection factors may have contributed to the observed responses , but it seems unlikely from these data that a clinical ly important drug interaction has occurred Objectives To compare the antihypertensive efficacy and tolerability of the imidazoline I1 receptor agonist moxonidine , a central ly acting antihypertensive , with the angiotensin converting enzyme inhibitor enalapril . Design An 8-week , double-blind , r and omized , placebo- controlled study involving 140 out patients with mild-to- moderate essential hypertension . Methods Out patients with WHO stage I or II hypertension were enrolled in the study . After a 4-week placebo-controlled stabilization phase patients were allocated r and omly to placebo , 0.2 mg moxonidine once a day or 5 mg enalapril once a day for 2 weeks . Dosages were then doubled to 0.4 mg moxonidine once a day or 10 mg enalapril once a day for a further 6 weeks . Blood pressure responses to therapy were measured by conventional office techniques and by 24 h ambulatory blood pressure monitoring . Results The mean reduction in sitting blood pressure  with moxonidine was similar to that with enalapril ( 19.5 ± 16.0/12.3 ± 8.7 versus 18.9 ± 13.7/11.8 ± 8.0 mmHg ) and significantly superior to that with placebo ( -4.6 ± 12.3/-4.7 ± 6.8 mmHg , P < 0.001 ) . In addition to reducing blood pressure during conventional measurements , moxonidine administration reduced blood pressure throughout 24 h ambulatory measurements . The trough : peak ratio for moxonidine was 0.7 . Both moxonidine and enalapril were tolerated well . Conclusions Moxonidine is an effective and well- tolerated antihypertensive , at least as good as other established forms of antihypertensive medication . The trough : peak ratio of 0.7 indicates that the drug will be effective administered once a day Thirteen patients with mild hypertension ( untreated diastolic blood pressure of 95 to 114 mmHg ) received , in r and om order , three successive treatments of four weeks with placebo , spirapril ( 6 mg daily ) , or hydrochlorothiazide ( HCT2 ) ( 24 mg daily ) . At the end of each treatment , blood sample s for assessment of platelet aggregation and platelet release of platelet factor 4 ( PF4 ) and for assessment of fibrinolysis , estimated by tissue plasminogen activator ( t-PA ) , plasminogen activator inhibitor-type 1 ( PAI-1 ) , and euglob ulin clot lysis time ( ECLT ) , were taken , first at rest , then immediately after five to ten minutes of vigorous exercise , and finally after the subsequent hour of recovery rest . Platelet aggregation induced in vitro by adrenaline significantly decreased during treatment with HCT2 , the threshold rising to 10 μM as compared with 1.0 with placebo ( P < 0.05 ) at rest , and the threshold for adenosine diphosphate ( ADP ) aggregation also rose , from 2 μM to 4 ( NS ) . The resting plasma PF4 value fell , although not significantly , during HCT2 treatment from the placebo value of 3.28 to 2.56 ng/mL. During spirapril treatment there was no change in the threshold of either adrenaline or ADP for aggregation of platelets sample d at rest , and the PF4 plasma levels showed no significant reductions at rest . However , during exercise PF4 showed an approximate doubling of the resting value irrespective of therapy . This exercise-induced increase in PF4 was significantly reduced by spirapril as compared with placebo ( P < 0.05 ) . ECLT and t-PA did not shift significantly from the placebo level during either therapy . PAI-1 did not change  during spirapril therapy , but during HCT2 treatment it fell , although not significantly , to 9.36 IU/mL from 15.91 with placebo ( NS ) . Spirapril and HCT2 did not produce any unwanted side effect on platelet function or fibrinolysis . HCT2 seems to decrease platelet activity at rest , whereas spirapril seems to some extent to decrease platelet activity at exercise The antihypertensive effectiveness of twice-daily dosing with the converting enzyme inhibitor , captopril , was examined in a multicenter study of 294 patients ( 181 white , 111 black , two oriental ) with essential hypertension whose supine diastolic blood pressure ( SDBP ) was 95 mm Hg or higher after 4 to 6 weeks of preliminary placebo administration . In this double-blind study , the patients were r and omized into one placebo and three captopril-treated groups : twice-daily placebo ( n = 77 ) or twice-daily captopril 25 mg ( n = 77 ) , 50 mg ( n = 71 ) , or 100 mg ( n = 69 ) . The average decreases in SDBP after 8 weeks of treatment were 5.2 % , 7.7 % , 11.7 % , and 10.5 % , respectively . Only the two higher dose groups differed significantly from the placebo group ; they also differed from the lowest dose group . The proportions of patients classified as having normalized pressures ( SDBP less than 90 mm Hg ) in the four groups were 39 % , 47 % , 70 % , and 50 % . If the results were analyzed by race , all three captopril-treated groups differed significantly from the placebo-treated group in the white patients but not in the black patients . However , direct comparisons between the white and black groups showed a difference only at the low , 25 mg twice daily ( b.i.d . ) , captopril dose . Thus , although conventionally given on a three-times daily basis , the twice-daily ( 12-hourly ) administration of captopril provides effective antihypertensive treatment in doses of 50 or 100 mg b.i.d . Moreover , white patients also exhibit a significant response to captopril at doses as low as 25 mg b.i.d . ( ABSTRACT TRUNCATED AT 250 WORDS The objective of the study was to examine the influence of angiotensin converting enzyme ( ACE ) inhibition on circulatory responses to st and ardized stress tests in primary mild to moderate hypertension . Patients ( n = 28 ) received 5 mg ramipril daily or placebo for 6 weeks in a double-blind crossover design , followed by 6 months of open ramipril treatment . Mental stress ( a 20-min Stroop 's color word conflict test ) and a cold pressor test were performed at the end of each of the three study periods . Noninvasive blood pressure and heart rate were recorded . Ramipril reduced systolic and diastolic blood pressure levels at rest ( from 146+/-3/99+/-3 with placebo to 135+/-4/94+/-3 at 6 weeks , and 136+/-4/91+/-3 mm Hg at 6 months , in the laboratory ) and during mental stress . Resting heart rates were unchanged by ramipril . Ramipril reduced systolic blood pressure and heart rate responses during mental stress ; diastolic blood pressure responses were unchanged . Ramipril reduced cardiac workload ( systolic blood pressure x heart rate ) levels and responses . Treatment effects at 6 months were generally greater than at 6 weeks . During the cold pressor test systolic and diastolic blood pressure levels were lowered by ramipril , but responses were unchanged . Heart rate responses , however , were reduced . Thus , ramipril reduced cardiac workload levels and responses also during the cold pressor test . These findings show that ACE inhibitors can reduce cardiac workload during stressful situations . If confirmed , this would seem to offer an advantage in the treatment of hypertension BACKGROUND Therapeutic agents for the treatment of hypertension may differ in their efficacy during the early-morning period , a time when both morbid and mortal cardiovascular events are increased compared with other times of the day . METHODS We studied the effects of a chronotherapeutic delivery system of verapamil ( controlled-onset extended release [COER]-24 system ) dosed at bedtime versus conventional morning administration of both enalapril and losartan on the blood pressure ( BP ) , heart rate , and the heart rate systolic BP product during the first 4 hours after awakening in a placebo-controlled , forced-titration trial . There were 357 men and women enrolled in the trial with an untreated sitting diastolic BP of 95 to 114 mm Hg and ambulatory daytime diastolic BP > or = 85 mm Hg . Patients were r and omized to either COER-verapamil hydrochloride each evening ( 240 mg titrated to 360 mg ) , enalapril each morning ( 10 mg titrated to 20 mg ) , losartan each morning ( 50 mg titrated to 100 mg ) , or placebo . Early morning assessment s of BP , heart rate , and the heart rate systolic BP product were performed by use of 24-hour ambulatory recordings after 4 weeks ( low dose ) and 8 weeks ( high dose ) of therapy . RESULTS Results were similar at weeks 4 and 8 for all treatment groups except that the magnitude of change was greater at week 8 . After 8 weeks of treatment , reductions in early morning BP by COER-verapamil were significantly greater ( -15/-10 mm Hg ) than enalapril ( -9/-7 mm Hg , P < .01 ) and losartan ( -8/-5 mm Hg , P < .001 ) . COER-verapamil also led to greater reductions in morning heart rate , the rate-pressure product , and the rate-of-rise of BP compared with the other 2 active treatment groups . Reductions in mean 24-hour BP were greater in patients treated with COER-verapamil compared with placebo and losartan , and similar to reductions in patients treated with enalapril . CONCLUSIONS Bedtime administration of an agent design ed to parallel the circadian rhythm of BP and heart rate led to significantly greater early morning hemodynamic effects compared with other conventional once-daily antihypertensive agents dosed in the morning To investigate the effects of antihypertensive treatment with the angiotensin-converting enzyme ( ACE ) inhibitor lisinopril on insulin sensitivity and related metabolic variables , the insulin sensitivity index ( SI ) , determined with the Minimal Model Method of Bergman , fasting plasma insulin and glucose concentrations , serum total triglyceride and lipoprotein cholesterol fractions , and blood pressure were assessed in 24 lean , non-diabetic patients with essential hypertension . Following a double-blind , r and omised crossover design , these parameters were measured after a 4-week run-in period , after 8 weeks of lisinopril or placebo , and after an additional 8 weeks on placebo or lisinopril , respectively . Furthermore , the level of physical fitness was estimated using the Conconi bicycle ergometer test . SI was low in this study population ( 5.6 vs 13.3 · 10−4·min−1·mU−1·1−1 in normal lean control subjects ) . It did not differ between the placebo run-in phase , the lisinopril phase , and the placebo crossover phase ( 5.8 , 5.5 , and 5.4·10−4·min−1·mU−1·1−1 , respectively ) . Moreover , during the administration of lisinopril , no significant changes occurred in fasting plasma insulin and glucose , areas under the glucose and insulin curves , glucose disappearance rate , serum total triglycerides , and cholesterol or lipoprotein cholesterol fractions . Heart rate at rest , body weight , and anaerobic threshold remained stable throughout the study . Compliance assessed by pill-counting exceeded 90 % at all visits . These findings demonstrate that the ACE inhibitor lisinopril is neutral with regard to insulin sensitivity , plasma insulin and glucose , and lipoprotein metabolism in patients with essential hypertension To assess the efficacy and time-dependent effects of once-daily moexipril , a nonsulfhydryl ester prodrug of the angiotensin-converting enzyme ( ACE ) inhibitor , moexiprilat , we conducted a multicenter , double-blind , placebo-controlled trial in 51 hypertensive patients using both clinic and ambulatory blood pressure ( BP ) recordings . Patients were included in the trial based on a minimum of 40 % of the daytime diastolic BPs of 90 mm Hg or more during a placebo baseline phase ; and the primary endpoint was change in  24-hour ambulatory diastolic BP .  Patients were r and omized to receive placebo , 7.5 mg of moexipril , or 15 mg of moexipril once daily . Clinic and ambulatory BPs were taken on the first day and after eight weeks of double-blind therapy . After the 7.5-mg dose , there were no significant changes in the acute or prolonged clinic BPs compared with placebo . Compared with adjusted mean changes for placebo , the 15-mg moexipril dose lowered clinic systolic BP , but not diastolic BP . In contrast , acute ( 1 day ) reductions in 24-hour diastolic BPs were -2/-3 mm Hg , -6/-4 mm Hg , and -14/-9 mm Hg on placebo , 7.5 mg of moexipril , and 15 mg of moexipril , respectively ( P < .01 for the 15-mg dose ) . Similarly , after long-term dosing for 8 weeks , reductions in 24-hour diastolic BPs were 1/-2 mm Hg , -6/-4 mm Hg , and -12/-9 mm Hg for the respective treatment groups ( P < .01 for the 15-mg dose ) . ( ABSTRACT TRUNCATED AT 250 WORDS Summary The pharmacodynamic effects and acceptability of perindopril ( 4 mg daily ) and hydrochlorothiazide ( 25 mg daily ) given alone or in combination for 1 month were investigated in a double-blind ,  placebo controlled , parallel group study . The pharmacokinetics of perindopril and its active metabolite perindoprilat and the time course of angiotensin converting enzyme inhibition were studied for 72 h following the last dose of treatment in the two appropriate groups . Similar decreases in blood pressure were seen 24 h after the last dose of perindopril or hydrochlorothiazide ( 11/7 mm Hg supine ) given alone at these doses . The effect of these drugs given together was additive on diastolic blood pressure and synergistic on systolic blood pressure ( 24.5/12.6 mm Hg supine ) taking into account the placebo response . The significant increase in plasma renin activity produced by perindopril alone was potentiated by concurrent administration of hydrochlorothiazide . The formation of  perindoprilat  was slightly reduced in the group also receiving hydrochlorothiazide and there was a very small reduction in ACE inhibition in this group . Perindopril , whether given alone or in combination with hydrochlorothiazide , was well tolerated and produced no clinical ly significant change in routine haematology or serum biochemistry . The additive or synergistic effects of perindopril and hydrochlorothiazide on blood pressure must be due to their complementary physiological actions and not to a pharmacokinetic interaction 1 . The role of angiotensin (Ang)II in and the effects of angiotensin‐converting enzyme ( ACE ) inhibitors on the regulation of sympathetic neural activity were examined in humans To investigate the concept of initiating therapy with low doses of a calcium antagonist and an ACE inhibitor , a fixed combination of isradipine 2.5 mg plus the ACE inhibitor spirapril 3 mg was compared with its components , with the full-dose monotherapies ( isradipine 5 mg or spirapril 6 mg ) , and with placebo . After a 2-week wash out phase in pretreated patients and a subsequent 2-week placebo period , 405 patients with a diastolic blood pressure ( DBP ) between 100 and 114 mmHg were r and omly allocated to 12-week once-daily double-blind treatment in one of the six treatment arms . In patients whose blood pressure was not normalized ( defined as DBP≤90 mmHg ) after 6 weeks of treatment , the dosage of either medication was doubled or , in the placebo group , was switched to the fixed combination . After week 6 , the mean reductions from baseline in sitting systolic/diastolic blood pressure 24 hours after dosing ( trough ) for the fixed combination or the monotherapies isradipine 5 mg , isradipine 2.5 mg , spirapril 6 mg , spirapril 3 mg , and placebo were10.4/8.7 , 10.0/9.4 , 6.5/6.7 , 10.0/8.3 , 7.0/5.8 , and 2.2/4.7 mmHg , respectively . The blood pressure changes obtained with the low-dose fixed combination were essentially identical to those observed with the full-dose monotherapies , thus showing an additive effect of low-dose isradipine and spirapril . In terms of tolerability , the lowest rate of any adverse events was found in the combination group . In this group , typical adverse events of calcium antagonists , such as headache , flushing , ankle edema , or palpitations , were observed only in 5 % , 2 % , 1 % , and 0 % , respectively , dry cough , considered typical for ACE inhibitors , was observed in only 1 % of the combination group . In conclusion , the low-dose components isradipine 2.5 mg and spirapril 3 mg were shown to have an additive effect when combined , exerting a blood pressure – lowering effect comparable with the full doses and a trend to a better tolerability profile in comparison with the st and ard doses . Thus , low-dose combination therapy with these drugs appears to be a rational alternative to conventional monotherapy in the first-line treatment of hypertension The responses of forearm bloodflow and heart rate to the Valsalva maneuvre were investigated in patients treated with placebo or cilazapril , a new angiotensin converting enzyme inhibitor . Twenty-four uncomplicated hypertensives , whose sitting diastolic blood pressures remained within 94 to 114 mmHg after four weeks of placebo therapy , were r and omly assigned on a double-blind basis to receive either further placebo or cilazapril ( 1.25 to 5.0 mg/day , single dose ) for a further four weeks . At the end of weeks 4 and 8 , each patient performed st and ardized Valsalva maneuvres before and 2 h after the day 's dose of medication . For each maneuvre , forearm bloodflow was measured in the resting phase and at the point of maximum tachycardia during the straining phase , together with a continuous record of heart rate . All patients exhibited the appropriate heart rate response to the maneuvre with marked tachycardia followed by bradycardia on release of straining . There were no differences in the degree of tachycardia , bradycardia or the Valsalva ratio as a result of cilazapril therapy . There were no changes in resting forearm bloodflow as a result of drug therapy but the flow was reduced ( P less than 0.01 ) during the straining period of all maneuvres . The relative decrease in flow during the maneuvre was attenuated ( P less than 0.05 ) in the cilazapril-treated patients at all drug doses but not in those taking placebo . Cilazapril appears to inhibit the sympathetic nervous system response to the baroreceptor stimulation of the Valsalva maneuvre but not the parasympathetic response of heart rate The hemodynamic effects of quinapril , a novel nonsulfhydryl‐containing angiotensin‐converting enzyme ( ACE ) inhibitor , were assessed in 10 patients with mild‐to‐moderate essential hypertension . Compared with placebo , quinapril ( 20 mg ) administered twice daily for 4 weeks significantly lowered blood pressure by decreasing total peripheral resistance without producing tachycardia , an increase in cardiac output , or a rise in plasma catecholamines . Quinapril significantly reduced renal , but not forearm , vascular resistance . Renal blood flow , glomerular filtration rate , and filtration fraction remained unchanged . Left ventricular wall stress was markedly reduced by quinapril , but during the relatively short treatment period , only a nonsignificant trend toward reduction in left ventricular mass was observed . These findings suggest that quinapril is an effective antihypertensive agent that lowers peripheral resistance without increasing cardiac output or disturbing autoregulation of renal hemodynamics OBJECTIVES To compare the antihypertensive efficacy and tolerability of the imidazoline I1 receptor agonist moxonidine , a central ly acting antihypertensive , with the angiotensin converting enzyme inhibitor enalapril . DESIGN An 8-week , double-blind , r and omized , placebo-controlled study involving 140 out patients with mild-to-moderate essential hypertension . METHODS Out patients with WHO stage I or II hypertension were enrolled in the study . After a 4-week placebo-controlled stabilization phase patients were allocated r and omly to placebo , 0.2 mg moxonidine once a day or 5 mg enalapril once a day for 2 weeks . Dosages were then doubled to 0.4 mg moxonidine once a day or 10 mg enalapril once a day for a further 6 weeks . Blood pressure responses to therapy were measured by conventional office techniques and by 24 h ambulatory blood pressure monitoring . RESULTS The mean reduction in sitting blood pressure with moxonidine was similar to that with enalapril ( 19.5 + /- 16.0/12.3 + /- 8.7 versus 18.9 + /- 13.7/11.8 + /- 8.0 mmHg ) and significantly superior to that with placebo ( -4.6 + /- 12.3/-4.7 + /- 6.8 mmHg , P < 0.001 ) . In addition to reducing blood pressure during conventional measurements , moxonidine administration reduced blood pressure throughout 24 h ambulatory measurements . The trough : peak ratio for moxonidine was 0.7 . Both moxonidine and enalapril were tolerated well . CONCLUSIONS Moxonidine is an effective and well-tolerated antihypertensive , at least as good as other established forms of antihypertensive medication . The trough : peak ratio of 0.7 indicates that the drug will be effective administered once a day This study evaluated the long-term effects of the angiotensin-converting enzyme inhibitor enalapril and the angiotensin II type 1 receptor antagonist losartan on the angiotensin-converting enzyme activity in T lymphocytes and plasma in patients with essential hypertension . The study was a r and omized , placebo-controlled , double-blind , crossover design . Nine patients with sitting blood pressure ≥ 95 mm Hg and ≤ 105 mm Hg at the end of a 4-week placebo run-in period entered the double-blind phase of the study , which consisted of three 6-week periods during which patients were treated with placebo , enalapril ( 20 mg , once daily ) , or losartan ( 50 mg , once daily ) The angiotensin-converting enzyme activity in T lymphocytes was measured as the activity of the degradation of the substrate Hippuryl-His-Leu and as the appearance of the dipeptide His-Leu , which was quantified spectrofluorometrically . Enalapril but not losartan suppressed ( p ≤ 0.01 ) the angiotensin-converting enzyme activity in plasma , whereas it stimulated ( p ≤ 0.05 ) the angiotensin-converting enzyme activity in circulating T lymphocytes . Our data document induction of angiotensin-converting enzyme in human T lymphocytes during long-term treatment with the angiotensin-converting enzyme inhibitor enalapril . Angiotensin II receptor type 1 antagonism with losartan had no effect on plasma or lymphocytic angiotensin-converting enzyme Cerebral blood flow ( CBF ) was measured in 13 subjects ( 4 men and 9 women , mean age + /- SD = 63 + /- 7 ) with moderate , uncomplicated and untreated hypertension and 11 normotensive subjects ( 6 men and 5 women , mean age + /- SD = 66 + /- 5 ) . A second CBF measurement was performed in hypertensive subjects after a 60 days r and omized double blind treatment with either captopril , 75 mg a day ( n = 8) or placebo ( n = 5 ) . CBF was quantified using the 133Xe inhalation technic and 16 stationary detectors by hemisphere . Comparison of CBF values between hypertensive subjects before treatment and normotensive subjects demonstrated a decrease of CBF in the hypertensive group ( 49 + /- 9 vs 72 + /- 14 ml/100 g/min ; p < 0.001 ) . After the trial the results in the captopril group showed a significant fall in systolic ( p < 0.001 ) and diastolic ( p < 0.05 ) blood pressure and a significant increase in CBF ( 60 + /- 14 vs 49 + /- 11 ml/100 g/min ; p < 0.05 ) . In the placebo group there was no change in blood pressure and CBF ( Table ) . [ Table ; see text ] Our results demonstrate a decrease in CBF of uncomplicated and untreated elderly hypertensive subjects . This decrease is reversible under chronic treatment with captopril Ramipril is a new , potent nonsulfhydryl inhibitor of angiotensin converting enzyme . The magnitude and duration of its antihypertensive effect were evaluated in a multicenter , placebo‐controlled , r and omized clinical trial conducted in 100 patients with mild to moderate essential hypertension .  Ramipril significantly reduced both supine and st and ing blood pressures measured 24 h after dosing . Automated blood pressure monitoring showed that ramipril significantly reduced systolic and diastolic pressures for 24 h after dosing . The peak effect occurred between 3 and 6 h after dosing , with approximately 50 % of this effect retained after 24 h. Ramipril was well tolerated ; there was no significant difference between active drug and placebo in the overall incidence of side effects . Ramipril is an effective and well‐tolerated antihypertensive agent , which reduces both supine and st and ing blood pressure over the entire 24‐h period after dosing The new angiotensin converting enzyme inhibitor enalapril ( MK-421 ) , was given in a single daily dose of 20 mg to 53 patients with uncomplicated essential hypertension . Its effects were compared with those of a placebo given to 47 patients on a double-blind r and omized basis . The blood pressure was measured in all patients by a physician , using a mercury sphygmomanometer , and by an automatic device in the absence of the physician . After 15 days of treatment , enalapril induced a significant reduction in systolic blood pressure ( 161.4 + /- 13 versus 145.1 + /- 15 , p less than 0.001 ) and in diastolic blood pressure ( 103.3 + /- 6 versus 92.9 + /- 8 , p less than 0.001 ) measured by the physician . The magnitude of the fall in blood pressure was identical after 30 days of active treatment . The reduction in blood pressure induced by enalapril was similarly detected by both methods of measurement , despite the fact that blood pressure values were higher when measured by the physician . A placebo effect was observed with the physician 's values that was not present with the automatically recorded values . A very significant correlation between blood pressure values obtained by these two methods was observed . However , among nine of 53 patients treated with enalapril , a difference in the decrease of blood pressure of 10 mm Hg or more was noted between the two methods of measurement . The decrease in blood pressure occurred with no change noted in the pulse rate or orthostatic hypotension . Plasma renin activity increased after treatment . No changes were observed in creatinine clearance and plasma electrolyte levels Despite a marked reduction in cardiovascular morbidity and mortality , treated hypertensive patients remain at increased risk of coronary artery disease and its complications compared with untreated normotensive subjects . Mild hypertension is often associated with other , usually chronic , diseases . The failure of first-line antihypertensive therapy to deal adequately with concomitant disease and associated therapy might account for the poor improvement in the cardiovascular prognosis . This possibility has been addressed in an ongoing trial of novel design , the Perindopril Therapeutic Safety Study , a multicenter , double-blind , r and omized and placebo-controlled trial to determine the safety , efficacy , and interaction of angiotensin-converting enzyme ( ACE ) inhibition with eight of the most common concomitant diseases and their therapies . A total of 480 male and female patients ( 60 per disease group ) aged 30 - 70 years , with a diastolic pressure of 90 - 104 mm Hg , were included after a 3-week placebo run-in if they satisfied st and ard criteria for any of the following : hyperlipidemia , type II diabetes , ischemic heart disease , cardiac arrhythmia , peripheral arterial disease , nephropathy with proteinuria , chronic obstructive lung disease , or rheumatoid arthritis . Of these , 460 patients have completed the 6-week double-blind phase ( comprising two assessment s , at 3 and 6 weeks ) , and are currently undergoing assessment s every 3 months over a 1-year follow-up period . The end points include the incidence of progression or improvement in concomitant disease , the incidence of positive or negative interaction between ACE inhibition and concomitant therapy , change in blood pressure , adverse biochemical and hemodynamic reactions , self-reported side effects , and quality of life indices . Interim results for the 6-week double blind phase will shortly be available . However , the desirability and feasibility of conducting a study according to this novel design have already been proved The effect of various antihypertensive medications on platelet function is of increasing interest . Conflicting effects of captopril on platelet function are reported and the impact of angiotensin converting enzyme ( ACE ) inhibitors not containing a sulfhydryl group such as enalapril , lisinopril , and quinapril on platelet function remains unstudied . Therefore , the aim of the present study was to examine the effect of antihypertensive treatment with quinapril , a novel ACE inhibitor not containing a sulfhydryl group , on platelet function . Ten white men ( age range of 32–61 years ) with untreated mild-to-moderate essential hypertension ( supine diastolic blood pressure > 95 mm Hg ) were treated with 4 weeks each of placebo and quinapril in a double-blind , r and omized , crossover design . Quinapril ( 20 mg twice a day ) significantly lowered systolic ( p < 0.01 ) and diastolic blood pressure ( p < 0.01 ) without any significant effect on heart rate or plasma catecholamines . No significant change was noted for in vitro platelet aggregation induced by epinephrine , ADP , or collagen . Plasma concentrations of the platelet release factors β-thromboglobulin and platelet factor 4 did not change , nor did the platelet content of norepinephrine , platelet weight ( mg/10 ml of blood ) , circulating platelet count , or platelet size . Thus , as assessed by a broad spectrum of platelet parameters , we found that antihypertensive treatment with quinapril has no significant effect on platelet function in patients with mild-to-moderate essential hypertension . These “ platelet-neutral ” properties of quinapril suggest that quinaparil , both from a thromboembolic and a hemostatic point of view , may be a rather safe agent for treatment of hypertension In this study we compared the antihypertensive efficacy and tolerability of captopril at 25 mg twice daily , hydrochlorothiazide ( HCTZ ) , 12.5 mg twice daily and placebo in a multicentre , double-blind , r and omized study that included 152 essential hypertensive patients ( 77 males , 75 females , 87 WHO stage I , 65 WHO stage II , aged 69 + /- 4 years , mean + /- s.d . ) .  Supine and st and ing blood pressure were similarly reduced by captopril and HCTZ ( P less than 0.01 for both compared with placebo ) . The heart rate did not change . Captopril ( 25 - 30 mg twice daily ) and HCTZ ( 12.5 mg twice daily ) , alone or in combination , maintained their antihypertensive effect during a 24-week single-blind follow-up study . During the follow-up , diastolic blood pressure remained less than 100 mmHg in seven essential hypertensives on placebo , in 45 on captopril and in 25 on HCTZ .  Side effects were observed in seven essential hypertensives during placebo ( treatment withdrawn in two ) , in eight during HCTZ and in three during captopril .  Serum potassium was reduced ( P less than 0.05 ) and uric acid was increased ( P less than 0.01 ) only during HCTZ . We conclude that captopril and HCTZ have similar antihypertensive efficacy in the elderly ; however , captopril appears to be better tolerated Objective : To compare the antihypertensive efficacy of moexipril , a new angiotensin-converting enzyme ( ACE ) inhibitor , to treatment with hydrochlorothiazide ( HCTZ ) . Patients : Two hundred and one non-hospitalized male and female patients between 65 and 80 years of age with essential hypertension . Methods : This was a multicentre , placebo-controlled , double-blind study with a parallel group design . Subjects with a sitting diastolic blood pressure ( DBP ) ≥ 95 mmHg were r and omized to monotherapy with placebo , moexipril 7.5 mg o.d . , moexipril 15 mg o.d . or HCTZ 25 mg o.d . for 8 weeks . Results : Throughout the study period treatment with moexipril and HCTZ result ed in significant reductions of DBP compared with placebo , but there were no significant differences between the active treatment groups . At end point the adjusted mean reductions were 10.5 , 8.7 and 10.1 mmHg in the HCTZ , moexipril 7.5 mg and moexipril 15 mg groups , respectively , compared to 3.9 mmHg in the placebo group . Treatment with moexipril was associated with two cases of first dose hypotension and two cases of moderate and reversible increases in serum creatinine levels . Otherwise , both dosages of moexipril were well tolerated and the overall percentages of patients who had adverse experiences were smaller than in the placebo group . Conclusion : Moexipril is well tolerated and is at least as effective as HCTZ in elderly patients with essential hypertension We assessed blood pressure ( BP ) and heart rate ( HR ) responses in a double‐blind , r and omized study comparing cilazapril , a long‐acting , nonsulfhydryl‐group converting enzyme inhibitor , with placebo in 18 patients with mild to moderate ( sitting diastolic BP , 95 to 114 mm Hg ) essential hypertension .  The BP and HR parameters were evaluated at rest ( casual , 24 hours after administration ) , during treadmill exercise testing ( Bruce protocol ) , and with 24‐hour noninvasive ambulatory BP monitoring . These assessment s were made after a 4‐week drug washout period and after 8 to 12 weeks of therapy . After 8 weeks of therapy with cilazapril ( mean dose 3.6 ± 0.9 mg/day ) , casual BP decreased 19/11 mm Hg ( p < 0.01 ) , whereas placebo  lowered BP by 4/5 mm Hg ( difference not significant ) compared with the baseline period . The casual HR was modestly ( 7 beats/min ) but significantly ( p < 0.05 ) lowered by cilazapril  monotherapy . Exercise BP was reduced by cilazapril ( reduction at peak HR , 23/11 ± 10/5 mm Hg ; p < 0.05 ) , and exercise HR was unchanged . Compared with baseline , the duration of exercise was improved with cilazapril but not with placebo ( 1.0 minute vs − 0.2 minute ; p < 0.05 ) . Twenty‐four‐hour mean , awake , and sleep BPs were reduced with cilazapril with the most impressive reduction occurring during the awake period ( 19/12 mm Hg ; p < 0.01 ) . These data demonstrate  that cilazapril  lowers casual , exercise , and ambulatory BP with a modest but significant improvement in exercise time . Thus cilazapril may be particularly effective in the physically active hypertensive patient Repeated blood pressure recordings by non-invasive devices are of better predictive value than single measurements in the evaluation of antihypertensive treatment . Such a method has been used to establish the dose-effect relationship of perindopril . After a two-week placebo run-in period , 40 patients with essential hypertension ( age 56.6 + /- 1.5 years , 31 males , nine females ) were treated with placebo or 2 , 4 or 8 mg of perindopril once daily for one month following a r and omized double-blind design . They were included if at least 75 % of diastolic blood pressure recordings , made over an 8 h diurnal period using an automatic blood pressure recorder , were greater than 95 mmHg on placebo . Values ( mean + /- SEM ) before and after treatment were assessed using analysis of variance . These data showed a significantly greater reduction of blood pressure with 4 mg and 8 mg daily doses compared to placebo and the 2 mg daily dose . Such results were not obtained with blood pressure levels recorded by a mercury sphygmomanometer , confirming the value of an automatic blood pressure recorder as a tool in therapeutic trials The subjects were 36 hypertensive patients aged 61 to 79 years ( mean , 66 years ) . After a placebo run-in period of one month , each patient was r and omly assigned to two months of treatment with 100 mg of metoprolol , 50 mg of captopril , or 25 mg of hydrochlorothiazide plus 2.5 mg of amiloride daily , or placebo . The doses were doubled if diastolic pressure was above 95 mm Hg after one month of treatment . Blood pressure , heart rate , and physical fitness ( endurance during a st and ard cycle ergometer exercise ) were measured and side effects assessed after each two-month treatment period . Mean blood pressures were significantly lower after treatment with metoprolol ( 154/92 mm Hg ) , captopril ( 157/92 mm Hg ) , and hydrochlorothiazide-amiloride ( 152/91 mm Hg ) than after placebo ( 170/101 mm Hg ) . Heart rate was significantly lower after treatment with metoprolol ( 64 beats/minute ) than after placebo ( 77 beats/minute ) . Exercise endurance was lower after treatment with metoprolol ( 498 seconds ) and hydrochlorothiazide-amiloride ( 519 seconds ) than after placebo ( 529 seconds ) and higher after captopril ( 541 seconds ) . More patients reached the target exercise work load after captopril than after the other treatments . No patients withdrew from treatment because of side effects or abnormal laboratory test results . All three active treatments benefited the elderly hypertensive patients and did not lower their physical fitness .  Captopril appeared to be more effective than the other two treatments The combination of an angiotensin converting enzyme inhibitor with a calcium antagonist has become a common way of treating patients with essential hypertension who respond insufficiently to monotherapy . This double-blind , r and omized , parallel , placebo-controlled , multicenter , outpatient study evaluated the antihypertensive efficacy and safety of a calcium antagonist ( verapamil SR ) and an angiotensin converting enzyme inhibitor ( tr and olapril ) in patients with mild-to-moderate ( stages I and II ) essential hypertension . Six hundred thirty-one patients were enrolled in this 10-week study . After a 4-week single-blind placebo phase , patients received one of the following daily dosage regimens in a double-blind fashion for 6 weeks : placebo , 4 mg of tr and olapril , 240 mg of verapamil SR , or a combination of 4 mg of tr and olapril and 240 mg of verapamil SR .  Trough sitting diastolic blood pressure was lowered by 4.5 mm Hg , 4.3 mm Hg , and 8.1 mm Hg more than placebo in the tr and olapril , verapamil SR , and combination groups , respectively . In the combination group , sitting diastolic blood pressure was significantly lowered ( P < .01 ) by 3.6 mm Hg more than in the tr and olapril group and by 3.8 mm Hg more than in the verapamil SR group . An analysis of the trough-to-peak ratio for sitting diastolic blood pressure revealed values of 0.75 and 0.67 , for the 4-mg tr and olapril and the combination groups , respectively , at end point . The overall incidence of adverse reactions was similar for all treatment groups . In this study the combination of an angiotensin converting enzyme inhibitor and calcium antagonist was well tolerated and more effective than either agent administered alone for the treatment of mild-to-moderate essential hypertension To determine the nature of the result ant effect on blood pressure when angiotensin converting enzyme ( ACE ) inhibitors are combined with other hypotensive agents in the treatment of uncomplicated essential hypertension , two r and omized , double-blind , crossover trials were conducted . In each trial there were four treatment phases , each 4 weeks in duration , comprising a 2 X 2 factorial experiment . Twenty-one patients completed the first study in which the effects of enalapril ( 10 mg twice daily ) were compared with hydrochlorothiazide ( 25 mg twice daily ) , with the two drugs in combination and with placebo . All blood pressure parameters were reduced in the three active treatment phases compared with placebo ( P less than 0.001 ) . Enalapril and hydrochlorothiazide were equally effective and in combination their hypotensive effects were fully additive . Sixteen patients completed the second study which compared the effects of enalapril ( 20 mg daily ) , atenolol ( 50 mg daily ) , the two drugs in combination and placebo . All blood pressure parameters were again reduced in all phases compared with placebo ( P less than 0.001 ) . Enalapril and atenolol were also equally effective , but in combination their hypotensive effects were less than fully additive , with attenuation of the potential additive response by 30 - 50 % . These results indicate that a diuretic-ACE inhibitor combination can be expected to have a greater hypotensive effect than a beta-blocker-ACE inhibitor combination . Both hydrochlorothiazide and atenolol increased plasma atrial natriuretic peptide ( ANP ) concentrations ( P less than 0.01 ) , suggesting that ANP could contribute to the hypotensive effects of these two drug classes A factorial design method was applied in this multicentre trial of the angiotensin-converting enzyme inhibitor quinapril hydrochloride ( Accupril ) in combination with the diuretic hydrochlorothiazide ( HCTZ ) to assess the additive effects of the combination versus monotherapy , to characterise the dose-response relationship of each drug in the presence of the other and to determine if quinapril would attenuate the hypokalemic effect of HCTZ . Following a two to four week placebo-baseline period , 460 qualifying patients with a DBP > or = 100 mmHg and < or = 115 mmHg were r and omised to an eight week double-blind phase with one of 16 parallel treatments : placebo , one of three doses of quinapril monotherapy , one of three doses of HCTZ monotherapy or one of nine possible corresponding combinations of quinapril and HCTZ .  Mean reductions in sitting SBP/DBP at trough with combination therapy ranged from 7.8 mmHg/7.2 mmHg to 19.6 mmHg/15.1 mmHg ( n = 458 ) . Results of the response surface analyses indicate that the effects of the two drugs were additive and that the maximum antihypertensive effect of quinapril in combination with HCTZ within the doses studied is achieved approximately at a dose of 26 mg quinapril and 25 mg HCTZ . The degree of attenuation of the hypokalemic effect of HCTZ was directly related to the dose of quinapril . At 40 mg quinapril , the HCTZ dose-related decreases of serum potassium were not apparent and overall hypokalemic effects were attenuated by quinapril . Thus , the combination of quinapril and HCTZ given once daily provided additive antihypertensive effects of predictable degrees and the addition of quinapril attenuated the hypokalemic effect of HCTZ BACKGROUND Endothelin is a powerful vasoconstrictor peptide derived from the endothelium . We evaluated the contribution of endothelin to blood-pressure regulation in patients with essential hypertension by study ing the effect of an endothelin-receptor antagonist , bosentan . METHODS We studied 293 patients with mild-to-moderate essential hypertension . After a placebo run-in period of four to six weeks , patients were r and omly assigned to receive one of four oral doses of bosentan ( 100 , 500 , or 1000 mg once daily or 1000 mg twice daily ) , placebo , or the angiotensin-converting-enzyme inhibitor enalapril ( 20 mg once daily ) for four weeks . Blood pressure was measured before and after treatment . RESULTS As compared with placebo , bosentan result ed in a significant reduction in diastolic pressure with a daily dose of 500 or 2000 mg ( an absolute reduction of 5.7 mm Hg at each dose ) , which was similar to the reduction with enalapril ( 5.8 mm Hg ) . There were no significant changes in heart rate .  Bosentan did not result in activation of the sympathetic nervous system ( as determined by measurement of the plasma norepinephrine level ) or the renin-angiotensin system ( as determined by measurements of plasma renin activity and angiotensin II levels ) . CONCLUSIONS An endothelin-receptor antagonist , bosentan , significantly lowered blood pressure in patients with essential hypertension , suggesting that endothelin may contribute to elevated blood pressure in such patients . The favorable effect of treatment with bosentan on blood pressure occurred without reflexive neurohormonal activation Summary : In a double-blind , placebo-controlled , parallel group study , 24 essential hypertensive subjects were r and omised to receive either placebo or 2 , 4 , or 8 mg perindopril . Perindopril , its deesterified metabolite , perindoprilat , and perindoprilat glucuronide were separated with an ion-exchange resin and determined by a radioimmunoassay ( RIA ) . Pharmacokinetic and pharmacodynamic parameters were estimated for 96 h after the first dose and after 4-week once-daily treatment . Perindopril peak levels were achieved in < 2 h after dosing with an elimination t1/2 of 1–2 h. Peak levels of perindoprilat were achieved more slowly , reaching a maximum level 5–8 h after dosing , and had an elimination t1/2 of 40 h. Levels of the perindopril glucuronide peaked ∼0.5 h later than perindopril , with an elimination t1/2 of ∼2 h. Perindopril , perindoprilat , and its glucuronide conjugate followed linear kinetics in the dose range of 2–8 mg , and there was no evidence of accumulation with chronic dosing . Perindopril 4 and 8 mg produced significant decreases in pre-dose blood pressure ( BP ) with chronic dosing , with maximal decreases occurring 5–7 h after dosing . Perindopril also produced a prolonged dose-dependent inhibition of plasma angiotensin-converting enzyme ( ACE ) activity that was maximum after 4 h and had not fully recovered by 48 h after a single dose The angiotensin-converting enzyme ( ACE ) inhibitor tr and olapril , a non-sulfhydryl prodrug which is hydrolysed into tr and olaprilat , was studied in 322 hypertensives of African – American descent using a double-blind , r and omised , placebo-controlled , parallel study design . Following 6 weeks of double-blind treatment with placebo or 0.25 to 16 mg/day tr and olapril , an analysis of drug effect on trough blood pressure ( BP ) stratified by age , gender , weight , pre-treatment plasma renin activity , and tr and olaprilat concentration was performed . Two mg was the lowest effective tr and olapril dose , whereas doses above 4 mg did not significantly reduce trough BP . Reduction in BP did not correlate with trough plasma tr and olaprilat concentration . Pre-treatment plasma renin activity was not a reliable indicator of antihypertensive response , as similar reductions in BP occurred even in patients with the lowest renin levels . There were no observable differences based on age , gender or measurements of the renin-angiotensin- aldosterone axis . In conclusion , neither age , gender or plasma renin activity influenced anti-hypertensive response to angiotensin-converting enzyme inhibition in African – Angiotensin-converting enzyme ( ACE ) inhibitors are increasingly used as first-line therapy for hypertension in type 2 diabetes mellitus and are widely believed to improve insulin sensitivity ( M ) . However , the evidence for the latter effect does not st and close scrutiny . We have assessed the effect of the ACE inhibitor tr and olapril on M in 16 patients ( mean + /- SD age , 58 + /- 10.6 yr ) with mild-to-moderate essential hypertension ( initial blood pressure , 173 + /- 14.5/93 + /- 8.0 mm Hg ) , obesity ( body mass index , 30 + /- 5.4 kg/m2 ) , and impaired glucose intolerance ( n = 4 ) or type 2 diabetes ( n = 12 ) in a double-blind , placebo-controlled crossover design . All patients underwent three 3-h euglycemic hyperinsulinemic clamp studies ( soluble insulin , 1.5 mU/kg x min ) after a 2-week placebo run-in and at the end of two 4-week periods of treatment with 2 mg tr and olapril or placebo ( 2-week washout ) . M ( mean + /- SD ) did not change with tr and olapril : placebo ( run-in ) , 5.2 + /- 1.98 mg/kg x min ; placebo , 5.3 + /- 1.70 mg/kg x min ; tr and olapril , 5.1 + /- 1.65 mg/kg x min ; P = 0.58 ; 95 % confidence intervals , -0.74 , 0.43 ( tr and olapril vs. placebo ) ; 95 % power to exclude an 8 % increase in M. In conclusion , tr and olapril had no clinical ly relevant effect on M in patients with hypertension and type 2 diabetes . Previous reports of improved M during ACE inhibitor treatment may be attributable to suboptimal study design and /or use of surrogate measures of BACKGROUND The objective of this study was to compare the antihypertensive efficacy and tolerability of c and esartan cilexetil ( CC ) with that of enalapril ( E ) and placebo ( P ) in hypertensives by clinic and ambulatory blood pressure ( BP ) .  PROCEDURES The study was an Italian multicenter , r and omized , double-blind , parallel group trial including 227 mild to moderate essential hypertensives ( age range , 18 to 70 years ) . After 4 weeks of P , patients were r and omized to 8 weeks of treatment with P or CC ( 4 mg ) or E ( 10 mg ) once daily , which was eventually increased to 8 mg and 20 mg once daily in nonresponders . At the end of each study phase , trough BP was measured by conventional sphygmomanometry and ambulatory BP was monitored over 24 h by a Spacelabs device . Analysis of 24-h BP profile included calculation of 24-h , daytime , nighttime , and hourly average values . RESULTS In the 178 patients evaluable per protocol , at the end of 8 weeks of treatment , trough systolic ( S ) and diastolic ( D ) BP were similarly reduced by both active treatments ( 13 + /- 12 and 10 + /- 7 mm Hg for CC and 14 + /- 12 and 10 + /- 7 mm Hg for E ) and significantly more by both treatments than by P ( 6 + /- 11 and 7 + /- 8 mm Hg , P < .01 v CC and E ) . In the 85 patients with valid 24-h recordings reduction in 24-h BP was again similar for the two active groups . The antihypertensive effect was still evident during h 23 and 24 after the last dose for both active treatments ( 8 + /- 20 v 5 + /- 18 mm Hg for SBP and 4 + /- 12 v 6 + /- 13 mm Hg for DBP , CC v E , respectively ) but not for P. Heart rate was not significantly modified by either active treatment . The incidence of adverse events was greater in the E than in the CC group . CONCLUSIONS Our study provides evidence that CC at a dose of 4 to 8 mg is as effective as E at a dose of 10 to 20 mg over 24 h , but is better tolerated than Summary In a double-blind , r and omized , multicenter study the antihypertensive efficacy of cilazapril 5.0 and 2.5 mg once daily vs. placebo was examined on 180 ambulatory hypertensive subjects with supine diastolic office blood pressure ( OBP ) 3 ≥ 95 and ≤ 115 mm Hg : a 4-week , single-blind , placebo period was followed by a 4-week double-blind treatment period . At the beginning and end of the latter , OBP measurements and ambulatory 24-h BP monitoring ( ABPM ) were both carried out on two different days ( 3 ± 1 ) , whereby each time two 24-h BP recordings were made using SpaceLabs 90202 . Measurements were made every 30 min , and actual waking and sleeping phase evaluation was done using diary entries . White coat hypertensive patients were excluded by the ambulatory BP ( ABP ) inclusion criterion : mean diastolic 24-h BP ≥ 85 mm Hg , or frequency of measurements > 90 mm Hg 5 ≥ 35 % . One-hundred eighty patients were included in the study . Safety was evaluated in 170 of these patients , and efficacy on OBP in 162 . Twenty-four-hour BP recordings that were amenable to analysis were available in the case of 146 patients ( average age 56 ± 10 years , 56 women , 90 men ) . The results of the main target variable for OBP , namely responder rates , were in the three treatment groups : placebo , 39.6 % ; cilazapril 2.5 mg , 55.6 % ; and cilazapril 5.0 mg , 65.5 % . All three treatment groups revealed a statistically significant effect ( p < 0.001 ) on the reduction of mean BP values : placebo from 161.6/102.2 to 149.4/94.7 mm Hg , cilazapril 2.5 mg from 162.9/102.1 to 149.7/92.0 mm Hg , and cilazapril 5.0 mg from 158.4/100.6 to 145.6/90.5 mm Hg . In contrast to OBP data , the analysis of the 24-h ABP profile showed a significant global antihypertensive effect on systolic and diastolic mean values only in the case of the two cilazapril dosages ( p < 0.001 ) . The drop in 24-h mean values was as follows : placebo from 148.3/91.7 to 146.1/90.1 , cilazapril 2.5 mg from 151.0/93.3 to 143.6/88.9 , cilazapril 5.0 mg from 148.0/92.2 to 140.8/86.1 . Analysis of the placebo effect using OBP measurement and ABPM led to completely opposing conclusions . In OBP measurement , a highly significant antihypertensive 24-h trough effect is simulated . In 24-h BP , the placebo effect is slight and restricted to a limited time interval ( approximately 8 h ) during the active waking phase . Both cilazapril groups had equipotent antihypertensive effects on systolic BP but distinctly dose dependent effects on diastolic BP . Both dosages demonstrated a continuous BP control , especially during the critical early morning waking-getting-up phase . Cilazapril 2.5 and 5.0 mg once daily was well tolerated AIMS The aims of this study were to examine the effects of tr and olapril , a long acting angiotensin converting enzyme ( ACE ) inhibitor with high tissue uptake , on insulin sensitivity and lipid concentrations in hypertensive patients with Type 2 diabetes mellitus . METHODS Insulin sensitivity was assessed after an acute dose ( day 3 ) and 19 days continuous treatment ( days 3 - 21 ) using the isoglycaemic , hyperinsulinaemic glucose clamp with D[3 - 3H ] labelled glucose , a variable D[3 - 3H ] priming dose and a ' hot ' glucose infusion .  Rates of glucose appearance ( Ra ) and glucose disappearance ( Rd ) were isotopically determined during the basal and insulin stimulated periods of the clamp . Twenty-four ( 5 female ) hypertensive ( blood pressure > 75th centile for age and sex ) patients with Type 2 diabetes mellitus were studied . Patients were r and omized , in a double-blind manner , to either tr and olapril 4 mg daily ( T ) or placebo ( P ) . RESULTS Baseline ( day 1 ) systolic ( mean + /- SD ; P 164+/-14 and T 168+/-13 mm Hg ) and diastolic ( P 93+/-6 , and T 98+/-10 mm Hg ) blood pressures were comparable . On days 3 and 21 , significant reductions were observed in both groups ( P<0.001 ) . In the tr and olapril-treated group , serum tr and olapril concentrations were > 200 pg/ml on days 3 and 21 , in all patients apart from one subject at a single visit , while tr and olapril was undetectable in the placebo group . Body mass index ( BMI ) was greater in T compared with P ( 32.2+/-5.4 v. 28.3+/-4.6 , P = 0.07 ) . After correcting for BMI , basal hepatic glucose output ( HGO ) P 2.6 ( 95 % CI 2.23 - 3.13 ) and T 1.91 ( 1.33 - 2.51 ) mg x kg(-1 ) x min(-1 ) and clamped HGO P 0.32 ( -0.44 - 1.09 ) and T 0.87 ( 0.40 - 1.34 ) mg x kg(-1 ) x min(-1 ) were similar in both groups . The insulin sensitivity index was comparable in both groups on all days . Total cholesterol concentrations were similar in both groups throughout the study . Triglyceride concentrations were significantly lower in group P 1.38 ( 1.07 - 1.68 ) ; T 2.14 ( 1.70 - 2.58 ) mmol/l , P<0.01 ) , no significant treatment effect being observed . CONCLUSIONS An acute dose and 19 days ' continuous treatment with tr and olapril result ed in no change in insulin sensitivity or plasma lipid profiles in patients with Type 2 diabetes mellitus and hypertension . These data support the metabolic neutrality of tr and olapril in patients with Type 2 diabetes mellitus and hypertension This multicentre , double-blind , parallel-group , placebo-controlled study compared the antihypertensive effects of equal doses of two long-acting angiotensin converting enzyme ( ACE ) inhibitors . After a two-week , placebo run-in phase , 110 patients with mild to moderate hypertension were r and omised to receive 10 mg lisinopril or enalapril , or placebo for 4 weeks . Office BPs were measured at regular intervals throughout the study . Twenty-four hour ambulatory blood pressure ( ABP ) was measured at baseline and after the first and final doses of study drug . Serum ACE activity and aldosterone were obtained concomitantly with each ABP monitoring . Office BP differences from placebo reached ( P less than 0.05 ) or approached ( P less than 0.10 ) statistical significance at all observations for the lisinopril group but were not significant for any observation in the enalapril group and approached significance on two occasions . After four weeks of treatment , ABP analysis revealed that the lisinopril and enalapril groups , when compared with placebo , had similar and significant systolic and diastolic AUC reductions ( P less than 0.01 ) from baseline over the 24 h dosing interval . During the second half of the dosing interval , 13 - 24 h post drug administration , the lisinopril group was significantly different from placebo ( systolic BP , P = 0.002 ; diastolic BP , P = 0.005 ) while the enalapril group was not . Both drugs were well tolerated . The results indicate that monotherapy with 10 mg of lisinopril is as effective as with 10 mg of enalapril , and that ABP monitoring is useful in more precisely depicting the clinical effect of the known pharmacokinetic properties of these two agents The efficacy of spirapril , 6 mg once daily , was compared with enalapril , 5–20 mg once daily , in the control of mild-to-moderate hypertension in a placebo-controlled , parallel-group study . A total of 251 patients participated in the study , all of whom underwent a 4-week washout period on placebo .  Thereafter , 100 patients were r and omized to spirapril , 6 mg once daily , 101 patients to enalapril , 5–20 mg once daily , and 50 patients remained on placebo .  Sitting diastolic blood pressure ( DBP ) and systolic blood pressure ( SBP ) were measured at 2-weekly clinic visits . Blood pressure profiles during peak and trough plasma drug concentrations ( 2–4 hours and 24 hours postdose , respectively ) were determined at baseline and 4 and 8 weeks after starting the double-blind phase . Compared with placebo , treatment with both spirapril and enalapril result ed in significant reductions ( p > 0.001 ) in DBP and SBP . DBP was reduced to a greater extent with spirapril than with enalapril both at peak ( −17.4 mmHg vs. −14.8 mmHg ) and trough ( −14.7 mmHg vs. −12.4 mmHg ) . Thus , although the trough/peak DBP ratios for spirapril and enalapril were very similar ( 84 % vs. 82 % ) , actual reductions in DBP were different . Spirapril and enalapril treatment result ed in similar reductions in SBP at both peak and trough levels . Both drugs were well tolerated , and there were very few adverse events or changes in hematological or biochemical parameters during the study . In conclusion , spirapril , 6 mg once daily , as the initial and maintenance dose , is at least as effective and well tolerated as enalapril individually titrated In 16 patients with essential hypertension the effects of enalapril 20 mg once daily were compared with those of atenolol 50 mg once daily , with the two drugs in combination and with placebo using a double-blind cross-over design with allocation of treatment order by r and omised Latin squares . For each patient there were four treatment phases , each of four weeks duration , which together comprised a 2 x 2 factorial experiment . All blood pressure parameters were reduced in the three active treatment phases compared to placebo ( p less than 0.001 ) . Supine blood pressures ( group means ) were 171/97 ( placebo ) , 147/85 ( enalapril ) , 154/84 ( atenolol ) and 144/78 ( enalapril plus atenolol ) ( S.E.M. + /- 2/+/- 1-ANOVA ) , and st and ing blood pressures were 170/105 ( placebo ) , 146/92 ( enalapril ) , 154/92 ( atenolol ) and 147/86 ( enalapril plus atenolol ) ( S.E.M. + /- 3/+/- 1 ) . In the combination phase there was an additional hypotensive response but the potential fully additive effects of the two agents were attenuated by 30 - 50 % . The mechanism of the attenuated hypotensive effect of the combined agents has not been determined . Plasma atrial natriuretic peptide ( ANP ) concentration was doubled in the presence of atenolol ( P less than 0.01 ) suggesting that ANP may contribute to the hypotensive effect of the beta-blocker AIMS To investigate the dose-response relationship and contribution of verapamil SR and tr and olapril given in combination once a day for the treatment of essential hypertension . METHODS A r and omized , double-blind , placebo controlled , factorial , 12 arm parallel group comparison with placebo , verapamil SR ( 120 , 180 mg ) , tr and olapril ( 0.5 , 1.0 , 2.0 mg ) covering all combinations of both drugs . A 4 week placebo run-in period followed by 6 weeks of treatment . Four hundred and fifty-six patients from office practice ( 22 centres ) with mild to moderate hypertension enrolled and 426 with diastolic pressure > or = 100 mm Hg at the end of run-in period were r and omized . Main outcome measures were reduction in sitting systolic ( SBP ) and sitting diastolic ( DBP ) blood pressure . RESULTS The combination of verapamil SR and tr and olapril , particularly verapamil SR 180 mg and tr and olapril 0.5 or 1.0 mg was significantly superior to both monocomponents at the same dose ( P<0.05 ) . For these combinations , the adjusted mean reductions in DBP from baseline to last visit were 14.1 and 16.0 mm Hg , respectively . Response surface analysis provided further evidence that these combinations were optimal for antihypertensive efficacy . All treatments were well tolerated . The incidence of adverse events did not differ significantly between treatment groups ; the profile of adverse events on combination therapy was mild and consistent with that of each monocomponent . CONCLUSIONS All dosage combinations of verapamil SR and tr and olapril produced significantly greater reduction of blood pressure than the monotherapy at the same dosage . However , verapamil SR 180 mg in combination with tr and olapril 1.0 mg was the dosage with the greatest blood pressure reduction and had the greatest effects compared with the monocomponents The aim of the present study was to assess the efficacy and tolerability of a calcium antagonist/beta-blocker fixed combination tablet used as first-line antihypertesnive therapy in comparison with an angiotensin converting enzyme inhibitor and placebo .  Patients with uncomplicated essential hypertension ( diastolic blood pressure between 95 and 110 mm Hg at the end of a 4-week run-in period ) were r and omly allocated to a double-blind , 12-week treatment with either a combination tablet of felodipine and metoprolol ( Logimax ) , 5/50 mg daily ( n = 321 ) , enalapril , 10 mg daily ( n = 321 ) , or placebo ( n = 304 ) , with the possibility of doubling the dose after 4 or 8 weeks of treatment if needed ( diastolic blood pressure remaining > 90 mm Hg ) . The combined felodipine-metoprolol treatment controlled blood pressure ( diastolic < or = 90 mm Hg 24 h after dose ) in 72 % of patients after 12 weeks , as compared with 49 % for enalapril and 30 % for placebo . A dose adjustment was required in 38 % of patients receiving the combination , in 63 % of patients allocated to placebo , and 61 % of enalapril-treated patients . The overall incidence of adverse events was 54.5 % during felodipine-metoprolol treatment ; the corresponding values for enalapril and placebo were 51.7 % and 47.4 % , respectively . Withdrawal of treatment due to adverse events occurred in 18 patients treated with the combination , in 10 patients on enalapril , and 12 patients on placebo .  No significant change in patients ' well-being was observed in either of the three study groups . These results show that a fixed combination tablet of felodipine and metoprolol allows to normalize blood pressure in a substantially larger fraction of patients than enalapril given alone . This improved efficacy is obtained without impairing the tolerability . The fixed-dose combination of felodipine and metoprolol , therefore , may become a valuable option to initiate antihypertensive treatment The aim of the study was to identify the most appropriate dosage combination of ramipril and felodipine ER ( an extended release tablet ) for mild-to-moderate hypertension . Hypertensive patients ( N = 507 ) with supinediastolic blood pressure ( DBP ) values between 100 - 115 mm Hg were included in a r and omized , multicenter , double-blind study of 3x4 factorial design with a 2 - 4 week single-blind , placebo run-in and 6 week active treatment phase . The patients were r and omized to 12 groups : placebo , ramipril ( 2.5 , 5 , 10 mg ) , felodipine ER ( 5 , 10 mg ) , or ramipril-felodipine ER combinations ( 2.5/5 mg , 2.5/10 mg , 5/5 mg , 5/10 mg , 10/5 mg , 10/10 mg ) . Although the greatest reductions in blood pressure were observed with ramipril-felodipine ER ( 10/10 mg ) , consideration of the antihypertensive efficacy and safety factors suggest that the ramipril-felodipine ER ( 5/5 mg ) combination has the best efficacy/tolerability ratio of the combinations tested . The incidence of adverse events with ramipril-felodipine ER  combination therapy was similar to that with felodipine ER monotherapy , but peripheral edema , tachycardia and vasodilatation occurred less frequently with ramipril-felodipine ER ( 5/5 mg ) combination than with felodipine ER monotherapy . The combination of ramipril-felodipine ER ( 5/5 mg ) can be considered to be the most suitable option for hypertensive patients with an inadequate response to either of the monocomponents The primary objective of this r and omised , placebo- controlled , double-blind , crossover study , was to evaluate and compare the longer term effects of the angiotensin II type 1 receptor antagonist losartan and the converting enzyme inhibitor enalapril on 24-h ambulatory blood pressure ( BP ) . After a 4-week placebo run-in period , nine patients with essential hypertension entered the double-blind phase of the study , which consisted of three 6-week periods during which patients were treated with placebo , enalapril 20 mg o.d . or losartan 50 mg o.d . Losartan and enalapril , taken between 07.00 and 08.00 , reduced ambulatory BP throughout the 24-h period . Average night time BP was reduced from 133/85 mm Hg on placebo to 124/78 mm Hg on enalapril and to 126/77 mm Hg on losartan . Daytime BP averaged 157/101 mm Hg on placebo , and was significantly lower during enalapril ( 142/91 mm Hg ) than during losartan treatment ( 147/95 mm Hg ) . Clinic BP , measured 2 to 4 hours after drug intake , was reduced to the same extent by both drugs . The losartan-induced BP changes were significantly related to those obtained with enalapril ( 0.63 < r < 0.93 ) . Ambulatory BP monitoring was repeated after 4 weeks of combined therapy in six patients . The BP lowering effect of the combination was not significantly better than that achieved with enalapril alone . In conclusion , losartan 50 mg o.d . and enalapril 20 mg o.d . lower BP to approximately the same extent , except for a more pronounced effect of enalapril on daytime ambulatory BP . The current study does not provide convincing evidence that addition of losartan to enalapril in the doses used further reduces BP 1 . Much attention has been given to the effects of various classes of antihypertensive drugs on blood pressure and haemodynamics . The effects of a single bout of exercise on post-exercise blood pressure have also been studied by several investigators . However , the combined effects of prior exercise and antihypertensive medication has drawn less attention . 2 . We examined the separate and combined effects of a single bout of exercise and of angiotensin converting enzyme ( ACE ) inhibition with a new ACE inhibitor ( fosinopril , 20 mg day(-1 ) ) on post-exercise blood pressure and systemic and regional haemodynamics .  Ten patients with mild-to-moderate hypertension were studied with a double-blind , r and omized crossover , placebo- and rest period-controlled study design . 3 . At rest , mean arterial pressure ( MAP , -10 + /- 2 mm Hg ) , total peripheral resistance ( TPR , -11 + /- 5 % ) and forearm vascular resistance ( FVR , -17 + /- 8 % ) were significantly ( P < 0.05 ) reduced during ACE inhibition as compared with the placebo phase . 4 . During the placebo phase , MAP ( -3 + /- 1 mm Hg ) , TPR ( -10 + /- 4 % ) and FVR ( -9 + /- 4 % ) were lower after exercise as compared with the control rest period . 5 . During ACE inhibition , MAP ( -3 + /- 1 mm Hg ) and TPR (-8 + /- 4 % ) were lower , but FVR ( + 32 + /- 15 % ) was increased after exercise as compared with the control rest period . 6 . Thus , blood pressure and TPR decreased similarly after exercise during the placebo phase and during ACE inhibition . However , differences in post-exercise forearm haemodynamics during the placebo phase and during ACE inhibition indicate that underlying regional haemodynamics are modified Angiotensin-converting enzyme ( ACE ) inhibitors are well established antihypertensives . Their effect on kidney function , however , seems to depend on the pathophysiological mechanisms underlying the clinical symptoms . In one part of the Perindopril and Therapeutic Safety Study ( PUTS ) the effect of a 6-week treatment with placebo or 4 mg/d of perindopril ( Coversum , CAS 82834 - 16 - 0 ) on kidney function and albuminuria was investigated in 56 hypertensives with concomitant nephropathy . The study was performed as multicenter , r and omized , placebo-controlled , double-blind study . The results show that perindopril reduced blood pressure effectively . The responder rate determined as a fall in blood pressure at least about 10 mmHg in the perindopril group was 39 % vs. 21 % in the placebo group . All investigated parameters of kidney function like serum creatinine , creatinine clearance , urinary excretion of albumin and alpha 1-microglobulin remained unchanged during the study . In a subgroup of patients with isolated albuminuria ACE inhibition reduced significantly the urinary albumin excretion  ( perindopril : -292 + /- 205 mg/g creat . vs. placebo : + 61 + /- 48 mg/g creat : p < 0.05 ) . From this study it can be concluded that in hypertension with concomitant nephropathy , except renovascular hypertension and hypertension in renal transplant recipients , ACE inhibition by perindopril will not impair kidney function . In the early phase of nephropathy with isolated albuminuria and normal serum creatinine perindopril improves albuminuria and seems to be even of benefit for the kidney Angiotensin-converting enzyme inhibitors and calcium antagonists are 2 classes of antihypertensive agents frequently used either as monotherapy or in combination . A 6-week , multicenter , r and omized , double-blind , placebo-controlled trial was conducted in essential hypertensive patients ( diastolic blood pressures [ BP ] when seated , 95 - 115 mm Hg ) to evaluate the efficacy , dose response , and safety profiles of enalapril combined with a new once-daily formulation of diltiazem .  BP and heart rate were measured at 5 ( peak ) and 24 ( trough ) hours after dose to assess the efficacy and pharmacodynamic profile of the combination given once daily . There were 336 patients r and omly assigned to either enalapril 5 mg plus 1 of 4 dose levels of diltiazem ER ( 60 , 120 , 180 , or 240 mg ) , enalapril 5 mg alone , or placebo . Each combination dose level produced statistically significant reductions ( p < 0.05 ) in trough diastolic BP when seated , compared with placebo ( -6.8 , -8.3 , -10.1 , and -10.3 mm Hg for the diltiazem ER doses of 60 , 120 , 180 , and 240 mg , respectively ) . The 3 highest combination dose levels result ed in statistically significant ( p < 0.05 ) decreases in trough diastolic BP when seated , compared with placebo . There was a significant ( p < 0.001 ) linear dose-response relation . A trough-to-peak ratio > or = 0.5 was shown for the 3 highest combination doses . Drug-related adverse events were seen in 8.9 % to 19 % of the combination patients , 14.3 % of the enalapril patients , and 8.6 % of the placebo patients . The frequency and type of adverse events were those currently noted with each drug studied when used as monotherapy The extent and the duration of the antihypertensive effect of captopril , given once a day at a dose of 50 mg , compared with placebo and with the 100 mg once daily dose was studied in 30 mild or moderate uncomplicated essential hypertensives ( mean ± s.e.m . age 52.0 ± 1.5 years ) , who responded ( mean blood pressure decrease > 10 % ) to a single oral dose ( 12.5 mg ) of captopril . According to a r and omized , double-blind , crossover design , they were given 50 mg captopril four times a day , 100 mg captopril four times a day or matched placebo for 1 month . At the end of each treatment period blood pressure and heart rate were measured every 30 min from 3 h before to 2 h after the last dose . Although the heart rate did not change , mean blood pressure after the 50− and 100-mg doses of captopril was consistently significantly ( P ± 0.05 ) lower than after placebo . The hypotensive effect peaked at the second hour and was still significant 24 h after dosing without any significant differences between the 50− and the 100-mg doses . These findings indicate that captopril , given chronically once a day at a dose of 50 mg to mild to moderate hypertensive responders , exerts its hypotensive effect up to 24 h and that doubling the dose does not increase either the extent or the duration of its action A factorial design was applied in this multicenter , double-blind , placebo-controlled trial of the calcium-channel blocker verapamil and the ACE inhibitor enalapril to assess the hypotensive effects of the combination compared with monotherapy , to evaluate safety , and to determine the effects on quality of life ( QOL ) of both drugs , alone and in combination . The study consisted of a 3 x 2 factorial design wherein 186 men and women with a sitting diastolic blood pressure ( BP ) of between 95 mm Hg and 114 mm Hg , after a 4-week placebo washout , were r and omized to one of six treatment groups for 4 weeks of active treatment . Monotherapy with both 240 mg verapamil and 10 mg enalapril reduced systolic and diastolic BP to a similar extent and significantly more than placebo . The 240 mg verapamil + 10 mg enalapril combination was additive for both systolic and diastolic blood pressure ; 120 mg verapamil + 10 mg enalapril was additive for systolic BP only . The total number of adverse events reported was similar for all six treatment groups . QOL scores were unchanged from baseline and not different between treatment groups . The combination of 240 mg verapamil and 10 mg enalapril was significantly more effective at reducing BP than either drug alone ; this additivity of effect was not linked to a higher rate of adverse experiences or to a deterioration in QOL . Thus , combination therapy at lower doses may offer an alternative treatment option to higher dose monotherapy The antihypertensive effect of the angiotensin-converting enzyme inhibitor tr and olapril administered in doses of 1 , 2 , and 4 mg/d was compared in 207 white patients and 91 black patients with mild to moderate hypertension following a double-blind , r and omized , placebo-controlled , parallel study design . Tr and olapril is a prodrug that is rapidly hydrolyzed to its active diacid metabolite , tr and olaprilat . After 6 weeks of double-blind treatment , tr and olapril lowered baseline sitting diastolic pressure in both white and black patients . A comparison of the antihypertensive response of the two population s revealed that the black patients required between two and four times the dose of tr and olapril to obtain a response similar to that observed in the white patients . A dose of 1 mg/d tr and olapril result ed in a 6.1 mm Hg mean decrease in baseline sitting diastolic pressure for white patients ; a similar response ( -6.5 mm Hg ) was observed in the black patients at 4 mg/d . In contrast to the population differences in blood pressure , the decreases in angiotensin-converting enzyme activity were similar for both population s. An evaluation of tr and olaprilat levels revealed that there were no racial differences in the tr and olaprilat concentrations required to achieve a given degree of angiotensin-converting enzyme inhibition . Therefore , it appears that the antihypertensive response of black patients is not completely explained by a reduction in angiotensin-converting enzyme activity . The lack of response at a lower dose but increasing response at a higher dose could reflect another vasodepressor activity of tr and olapril or just be evidence of reduced sensitivity of high blood pressure in blacks to angiotensin-converting enzyme inhibition The antihypertensive effect and safety of fosinopril and hydrochlorothiazide combined were compared with each drug singly and placebo in a controlled manner . After a 4- to 5-week placebo lead-in period , 67 mild to moderate essential hypertensive patients ( seated diastolic blood pressure £ 95 and £ 110 mm Hg ) were r and omized in a double-blind fashion into four parallel treatment groups : 20 mg fosinopril plus 12.5 mg hydrochlorothiazide , 20 mg fosinopril , 12.5 mg hydrochlorothiazide , and placebo during 8 weeks . Patients were seen biweekly . Sitting diastolic blood pressure was the outcome variable defining therapeutic response . The efficacy  of fosinopril plus hydrochlorothiazide as a combined therapy was superior to any single drug ( P<.05 ) and placebo ( P<.01 ) in the treatment of mild to moderate essential hypertension . Mean adjusted systolic/diastolic blood pressure decrements at week 8 were −18.8/−13.7 , −12.9/−11.8 , −8.5/−9.3 , and −2.11−6.9 mm Hg for the fosinopril plus hydrochlorothiazide , fosinopril , hydrochlorothiazide , and placebo groups , respectively . Clinical adverse events and laboratory changes documented throughout the study were similar to placebo and were mild in severity in all groups 1 In a r and omised study , 475 men with diastolic blood pressures of 92 - 109 mm Hg received either placebo or captopril 37.5 mg , 75 mg or 150 mg/day for 7 weeks . 2 After 7 weeks patients taking placebo were given hydrochlorothiazide 25 mg twice daily , as were two-thirds of each group taking captopril and they were observed for 7 additional weeks . 3 Captopril reduced blood pressure by 12.2 + /- 0.8/9.4 + /- 0.4 mm Hg at 7 weeks ( n = 323 ) and captopril plus placebo reduced it by 10.3 + /- 1.9/10.2 + /- 0.9 mm Hg at 14 weeks ( n = 83 ) ; placebo by 2.0 + /- 1.7/3.4 + /- 0.8 mm Hg ( n = 76 ) ; and captopril plus hydrochlorothiazide by 24.4 + /- 1.1/16.2 + /- 0.6 mm Hg ( n = 173 ) . The effect of low-dose captopril was similar to that of high doses . 4 White patients responded better than blacks , with a blood pressure reduction of 14.7 + /- 1.1/10.7 + /- 0.6 mm Hg ( n = 170 ) v 9.1 + /- 1.2/8.0 + /- 0.7 mm Hg ( n = 151 ) . This difference was abolished by the addition of hydrochlorothiazide . 5 Only 15/384 ( 3.9 % ) of patients were dropped from the study because of adverse effects . 6 The prescription of low-dose captopril might be extendable to patients with mild to moderate hypertension Arterial hypertension may be associated with altered left ventricular filling dynamics . The specific goal of this study was to evaluate whether short-term administration of the ACE inhibitor lisinopril in hypertensive patients with an altered diastolic pattern induced an improvement of left ventricular dynamics , assessed by the echocardio-Doppler technique , independently of effects on left ventricular mass . In a double-blind cross-over study 39 essential hypertensive patients with a ratio of peak early to peak atrial velocity ( E/A ) < 1 were r and omized , after a run-in period of 2 weeks without any antihypertensive treatment , to receive lisinopril ( 20 mg once a day ) and placebo for 4 weeks , respectively . At the end of both the run-in and the treatment periods , blood pressure and heart rate were measured and an echocardio-Doppler examination was carried out . The echocardio-Doppler evaluation was performed both at rest and at the peak of a h and -grip test ( 3 min at 30 % of maximal strength ) . Left ventricular dimensions were obtained from two-dimensionally guided M-mode tracings using the criteria of the American Society of Echocardiography . Left ventricular peak filling rates and filling rate integrals were measured by a pulsed Doppler technique . Lisinopril caused a significant reduction in systolic and diastolic blood pressure at rest ( -13/-9 mmHg vs baseline values , p < 0.05 ; -6/-4 mmHg vs placebo values , p < 0.05 ) and during isometric exercise ( -17/-9 mmHg vs baseline period , p < 0.05 ; -6/-5 mmHg vs placebo , p < 0.05 ) . Lisinopril did not induce any significant change in left ventricular structure and systolic function . All the left ventricular filling parameters considered ( E velocity , A velocity , E/A ratio ) both at rest and during isometric exercise did not significantly differ after lisinopril treatment when compared to those obtained in basal conditions and after placebo administration . This double-blind cross-over study demonstrates that short-term afterload reduction induced by lisinopril does not modify altered diastolic dynamics in hypertensive patients . Diastolic dysfunction of the left ventricle is a complex process influenced by a number of functional and structural factors and apparently can not be significantly improved by short-term blood pressure reduction by antihypertensive therapy The safety and efficacy of two fixed dose combinations of enalapril and diltiazem extended release formation ( ER ) ( E/D ) were compared with their monotherapies and placebo in patients with stage 1 to 3 hypertension . The trial design was a multicenter , r and omized , double blind , placebo controlled , parallel group , 12 week treatment phase , followed by a 36 week , open label phase . A total of 891 patients with sitting diastolic blood pressure ( SiDBP ) between 95 and 115 mm Hg were r and omly assigned to enalapril 5 mg , diltiazem ER 120 mg , diltiazem ER 180 mg , enalapril 5 mg/diltiazem ER 120 mg ( E5/D120 ) , enalapril 5 mg/ diltiazem ER 180 mg ( E5/D180 ) , or placebo . In the open label phase , 562 patients received the fixed combination , titrated as needed to control SiDBP < 90 mm Hg . Efficacy was determined with trough ( 24 + /- 2 h postdose ) sitting blood pressure measurements at week 12 and at the end of the open label part of the study . Safety was evaluated based on patient symptoms , clinical laboratories , and electrocardiograms ( ECG ) . E5/D120 and E5/D180 significantly reduced trough SiDBP ( -7.6 and -8.3 mm Hg , respectively ; P < .05 ) versus their monotherapies . E5/D120 and E5/D180 significantly reduced trough sitting systolic blood pressure ( -7.9 and -9.0 , respectively ; P < .05 ) versus both diltiazem ER monotherapies . All active treatments significantly decreased SiDBP and SiSBP versus placebo . E/D effectively lowered SiDBP and SiSBP during the open label extension . No significant difference was seen among treatment groups for the overall incidence of adverse events . The most common drug related adverse events were headache , edema/swelling , dizziness , asthenia/fatigue , cough , rash , and impotence . The event frequency for the combinations were similar to those seen with the monotherapies . Fixed combinations of E/D were generally well tolerated , with an increased blood pressure lowering effect as compared with the individual components in patients with stage I to III hypertension The aim of this study was to evaluate the effects of tr and olapril on 24-hour blood pressure in patients with mild-to-moderate essential hypertension . After a washout period of 4 weeks , 42 patients were r and omized to receive 2 mg of tr and olapril once daily and 20 to receive placebo in a double-blind fashion for 6 weeks . This was followed by a second washout period of 4 weeks . At the end of each period , clinic blood pressure was assessed at 24 hours after the last dose and 24-hour ambulatory blood pressure was measured noninvasively , taking blood pressure readings every 15 minutes during the day and every 20 minutes during the night . Two patients were dropped out before any blood pressure evaluation under treatment . Analysis of ambulatory blood pressure was performed in 48 patients who met the criteria for the minimal number of ambulatory blood pressure data ( 2 values per hour during the day and 1 value per hour in the night ) . In the tr and olapril-treated group ( n = 41 )  clinic systolic/diastolic blood pressures were 159.8 + /- 2.0/102.4 + /- 0.8 , 146.8 + /- 2.3/94.8 + /- 1.1 , and 155.7 + /- 2.0/99.2 + /- 0.7 mm Hg in the pretreatment , treatment , and post-treatment periods , respectively . The corresponding values for 24-hour mean blood pressure ( n = 31 ) were 139.5 + /- 1.9/91.2 + /- 1.5 , 131.0 + /- 2.0/84.3 + /- 1.2 , and 139.7 + /- 1.8/90.9 + /- 1.1 mmHg . The differences between the lower treatment , versus the higher pre- and post-treatment , values were all statistically significant ( p < 0.01 ) . ( ABSTRACT TRUNCATED AT 250 WORDS This study evaluated the blood pressure effects of administration of once daily oral benazepril hydrochloride , a new angiotensin‐converting enzyme ( ACE ) inhibitor , for mild‐to‐moderate hypertension . After a 2 to 4 week placebo baseline period , patients with diastolic blood pressure between 95 and 114 mm Hg , were r and omized to receive either placebo or benazepril hydrochloride , 5 , 10 , 20 , or 40 mg , once daily in double‐blind fashion for 28 days . Blood pressure was measured predose and at 1 , 2 , 3 , 4 , 6 , 8 , 12 , 16 , 20 , and 24 hours after the dose during inpatient observation days at the end of the placebo baseline period , and on the first and last day of the double‐blind treatment period ; and 24 hours after the dose at weekly outpatient visits . All doses of benazepril hydrochloride result ed in clinical ly important reductions in diastolic and systolic blood pressures that lasted between 12 and 24 hours after both the first dose , and following the last dose after 4 weeks of treatment . The findings indicate that benazepril hydrochloride may be clinical ly useful as once‐daily monotherapy in many patients with hypertension OBJECTIVE To determine the quality of life ( QOL ) of mild hypertensive patients treated with captopril as compared to placebo . METHODS This is a r and omized , double-blind , placebo-controlled clinical trial held in the out-patient clinic of Zhong Shan Hospital . Adult patients aged from 28 to 75 years with mild hypertension defined as diastolic blood pressure from 90 to 105 mm Hg were the inclusion criteria of the study . There were 278 patients who were eligible to enter the study . They were r and omized to receive captopril or placebo 25 to 50 mg bid for 12 weeks . Change of QOL was compared both quantitatively and qualitatively between captopril and placebo groups . Change of blood pressure and side effects were also compared . RESULTS With intention-to-treat analysis , significantly more improved QOL patients could be found qualitatively in patients with captopril treatment ( 45.3 % vs 23.7 % , P = 0.0002 for physical health domain ; 48.9 % vs 26.6 % , P = 0.0002 for mental health domain ; 33.8 % vs 11.5 % , P = 0.0001 for general function domain ) . Quantitatively , the change of score of mental health , general function and total QOL of captopril ( 3.18 + /- 5.90 ; 1.65 + /- 4.43 ; 7.84 + /- 11.03 ) were significantly higher than those of placebo ( 1.32 + /- 5.13 , P = 0.00004 ; 0.64 + /- 3.45 , P = 0.0008 ; 4.19 + /- 10.33 , P = 0.0025 respectively ) , and the change of score of physical health domain ( 3.01 + /- 5.26 vs 2.23 + /- 4.79 , P = 0.044 ) was of borderline statistical significant difference . Blood pressure was significantly lowered by captopril than by placebo ( P = 0.000 ) . CONCLUSION Compared with the placebo , captopril is not only effective in lowering blood pressure , as has been established , but also effective in improving QOL in mild hypertensives The antihypertensive efficacy of 2.5 and 5 mg cilazapril and placebo in lowering 24-h ambulatory blood pressure ( ABP ) and BP load were compared in 42 patients with mild to moderate hypertension . After a 2-week placebo run-in period , patients were r and omized double-blind to receive either 2.5 mg cilazapril ( n = 14 ) , 5 mg cilazapril ( n = 14 ) , or placebo ( n = 14 ) for 4 weeks . There were no significant differences in 24-h and awake ABP or in office BP between 2.5 and 5 mg cilazapril . Moreover , the percentage of patients that had BP control ( mean daytime ABP less than 90 mm Hg ) was 14 % in the placebo group , 64 % and 71 % with 2.5 and 5 mg cilazapril , respectively . Furthermore , the percentage of BP load was similar with both regimens ( 29 v 36 % ) . These observations indicate that 2.5 and 5 mg cilazapril have equipotent antihypertensive efficacy Objective : To compare the efficacy , safety and tolerability of valsartan to an angiotensin-converting enzyme ( ACE ) inhibitor , lisinopril , and placebo in patients with mild-to-moderate essential hypertension . Design : A total of 734 men and women were r and omised in this multicentre , double-blind , optional titration , parallel group trial . Volunteers received valsartan 80 mg ( n = 364 ) , lisinopril 10 mg ( n = 187 ) or placebo ( n = 183 ) daily for 4 weeks , with subsequent titration of dose depending on response to treatment ( valsartan 80 mg titrated to valsartan 160 mg once daily or valsartan 80 mg twice daily , lisinopril 10 mg titrated to lisonopril 20 mg once daily ) . Patients were assessed at 4 , 8 and 12 weeks . Main outcome measures : The primary variable was change from baseline in mean sitting diastolic blood pressure ( SDBP ) . Other efficacy variables included sitting systolic blood pressure ( SSBP ) and percentage of ‘ successful ’ responders ( SDBP < 90 mm hg or ⩾10 mm hg reduction from baseline ) . Results : All active treatment groups were shown to demonstrate significant reductions in SDBP compared to placebo at endpoint of therapy ( least mean square reduction from baseline : valsartan 80/160 mg : −5.25 mm Hg ( CI −7.17 , −3.34 , P < 0.001 ) ; valsartan 80/80 mg twice daily : −5.63 mm hg ( ci −7.51,−3.75 , P < 0.001 ) ; lisinopril 10/20 mg : −6.93 mm hg , ( ci −8.81 , −5.05 , P < 0.001 ) . there were no statistically significant differences between the active treatment groups at endpoint of therapy . in patients requiring titration to a higher dose ( placebo n = 142 , valsartan 80/80 twice daily n = 124 , valsartan 80/160 n = 114 , lisinopril 10/20 n = 120 ) , there were no significant treatment differences between valsartan 160 mg given as a single daily dose or as 80 mg twice daily ( P = 0.658 ) . Both valsartan and lisinopril produced similarly high percentages of ‘ successful ’ responders at endpoint of therapy . A somewhat higher frequency of drug related cough was observed in lisinopril treated patients ( 8 % ) compared to valsartan ( 1.1 % ) or placebo ( 0.5 % ) . Conclusions : Valsartan 80 mg daily , with titration to 160 mg daily as required , provides similar antihypertensive efficacy to lisinopril 10 mg daily with titration to 20 mg daily . Valsartan provides a new antihypertensive agent with comparable efficacy to lisinopril and appears to be associated with a reduced incidence of cough Summary : Twenty-two patients with essential hypertension received a single dose of 2.5 mg cilazapril and were then r and omised into a double-blind parallel group study to receive either placebo , 1.25 mg cilazapril + 0.5 mg cyclopenthiazide ( CPTZ ) , 2.5 mg cilazapril + 0.5 mg CPTZ , or 2.5 mg cilazapril alone for 1 month . After oral administration of a single dose of 2.5 mg cilazapril , the active diacid cilazaprilat appeared rapidly in the plasma ( Tmax 2.0 ± 0.2 h ) . With the radioinhibitor assay used in this study , a single elimination phase of cilazaprilat was evident , with a half-life ( t1/2 ) of 2–3 h. At steady state , the pharmacokinetics of cilazaprilat were similar to single-dose administration and were not altered by CPTZ . The Cmax and area under the curve ( AUC ) of cilazaprilat were directly proportional to dose . Cilazapril administration in the dose range of 1.25–2.5 mg produced a dose- proportional inhibition of angiotensin-converting enzyme ( ACE ) activity that was maximum 2 h after drug administration . The degree of ACE inhibition correlated with the plasma concentration-time profile of cilazaprilat and the maximum decrease in blood pressure ( BP ) . The EC50 for ACE inhibition by cilazaprilat was 7.7 ng/ml after acute treatment and was not significantly altered during chronic administration or by concomitant administration of CPTZ . There was no evidence of a dose-related anti-hypertensive effect of cilazapril at steady state and , with the small numbers of subjects used in this study , there was no evidence of 24-h BP control with monotherapy Summary : The antihypertensive effect of the angiotensin-converting enzyme ( ACE ) inhibitor lisinopril administered in a single dose of 20 mg was evaluated by ambulatory blood pressure monitoring ( ABPM ) in a double-blind , placebo-controlled , cross-over study . Twenty-four patients ( 21 men and 3 women , mean age 52 ± 6 years ) with mild to moderate hypertension were included in the study and r and omly assigned to two consecutive treatments with lisinopril 20 mg and placebo , each administered for 4 weeks . On the last day of each treatment , BP was assessed by noninvasive 24-h ABPM . BP was significantly lower  after lisinopril than after placebo in a 24-h period ( mean 24-h systolic BP ( SBP )  with lisinopril 120 ± 7 mm Hg and with placebo 135 ± 9 mm Hg ; mean day SBP with lisinopril 125 ± 3 mm Hg and with placebo 142 ± 5 mm Hg ; mean night SBP with lisinopril 112 ± 4 mm Hg and with placebo 124 ± 6 mm Hg ; mean 24-h diastolic BP ( DBP )  with lisinopril 76 ± 6 mm Hg , and with placebo 87 ± 8 mm Hg ; mean day DBP  with lisinopril 80 ± 3 mm Hg and with placebo 93 ± 4 mm Hg ; mean night DBP  with lisinopril 69 ± 2 mm Hg and with placebo 79 ± 5 mm Hg , p < 0.001 ) . Mean 24-h , mean day , and mean night heart rate ( HR ) did not differ significantly between placebo and lisinopril treatments . Repeated- measures analysis of variance ( ANOVA ) showed a significant influence on SBP ( p 0.001 ) and DBP ( p < 0.001 ) throughout the treatment . A significant time effect was also evident both for SBP ( p 0.001 ) and DBP ( p < 0.001 ) . The interaction of time and treatment was not significant , suggesting that the circadian rhythm of BP was not different during the two treatments . No serious side effects were observed during this study The antihypertensive efficacy of ramipril was evaluated using 24-h noninvasive ambulatory sphygmomanometry in this double-blind , placebo-controlled study . One hundred subjects with mild-to-moderate essential hypertension were r and omized to ramipril , 10 mg or placebo once daily for a 4-week treatment period . Ramipril decreased systolic and diastolic blood pressures throughout the 24-h period after dosing . Blood pressures measured manually 24 h postdose also showed that ramipril significantly reduced supine and st and ing blood pressures when compared with placebo . Incidences of adverse events were similar in the two study groups . Ramipril proved to be a well-tolerated agent with a sustained 24-h antihypertensive effect in this study Serum lipids of 80 patients with moderately severe essential hypertension under four different antihypertensive therapies were compared to ten matched hypertensives on a placebo  , after eight weeks of therapy . The results in the serum lipid parameters measured after therapy showed with enalapril a significant increase in high-density lipoprotein cholesterol ( HDL-C ) and a decrease in the total cholesterol/HDL-C ratio . With benazepril a significant decrease in the total cholesterol/HDL-C ratio was obtained . With the diuretic combination Epitens the effect on serum sodium and potassium was minimal . No significant changes were found in the lipoprotein profile following the administration of the placebo . Both angiotensin converting enzyme inhibitors ( enalapril and benazapril ) induced a significant improvement in the atherogenic ratio ; as well as the calcium antagonist ( isradipine ) , though to a less extent . The diuretic Epitens induced an insignificant deterioration of the atherogenic ratio Benazepril hydrochloride is a new angiotensin‐converting enzyme inhibitor . In a multicenter study , 206 patients with mild to moderate hypertension were r and omized to receive benazepril at a dose of 2 , 5 , 10 , or 20 mg , hydrochlorothiazide , 25 mg , or placebo once daily for 4 weeks . The 20 mg dosage of benazepril  lowered blood pressure to a degree equal to that of 25 mg hydrochlorothiazide : −12.217.7 mm Hg and −13.4/−7.5 mm Hg , respectively . Hydrochlorothiazide proved to be more effective in black subjects . At lower dosage levels of benazepril ( 2 , 5 , and 10 mg ) , blood pressure reduction was not significantly different from that with placebo . In those patients who failed to achieve goal diastolic blood pressure of < 90 mm Hg with monotherapy after 4 weeks , the addition of open‐label hydrochlorothiazide ( 25 mg/day ) to benazepril , hydrochlorothiazide , or placebo produced a substantial additional decrease in blood pressure over a 2‐week period . No definite adverse effects on hématologie measurements , serum biochemistry test results , or urinalyses were noted . Subjective adverse experiences were common in all groups but except in three or possibly four instances were not considered causally related to the study drug Although it has been recognized that enalapril lowers blood pressure by reducing the total peripheral vascular resistance , its direct effect on blood vessels is largely unknown . Little information is available about the influence of enalapril on the different vascular regions . Ten patients with moderate essential hypertension were treated with enalapril 20 mg daily in a double-blind , placebo controlled cross-over study for six weeks during each period . Blood pressure and heart rate were measured in supine , sitting and st and ing position . Venous capacity was derived from pressure volume curves plotted simultaneously at forearm and calf . Arterial blood flow at rest and during reactive hyperemia was measured at calf and finger by plethysmography . Enalapril increases venous capacity in upper and lower limbs in patients with moderate essential hypertension . Also , there is vasodilation of calf and finger arteries both at rest and during reactive hyperemia . Finger and calf arteries contribute to the decrease of the total peripheral vascular resistance during treatment with enalapril ; thus , ACE inhibition is capable of correcting the increased peripheral resistance which often is the main cause of arterial hypertension The use of ambulatory blood pressure monitoring in clinical studies offers some advantages in comparison to the clinic blood pressure measurement . In fact , this approach does not induce any alerting reaction and provides 24-h blood pressure values that are more reproducible and not affected by the placebo effect . This allows a better evaluation of blood pressure under antihypertensive treatment and an optimization of the number of patients to be studied in pharmacologic trials . In a recent double-blind , parallel-group study , ambulatory blood pressure monitoring was used to investigate the antihypertensive efficacy of a new angiotensin-converting enzyme inhibitor , tr and olapril , in 62 mild and moderate hypertensive patients . After a washout period , patients received tr and olapril , 2 mg o.d . , or placebo for 6 weeks , followed by a second washout period . Clinic and 24-h blood pressures were assessed at the end of each period . In comparing the pre- and post-treatment period , tr and olapril significantly reduced clinic and 24-h systolic and diastolic blood pressures . The fall was evident throughout the 24 h and was statistically significant also in the last 4 h of blood pressure monitoring . The placebo group did not show any significant blood pressure change . Thus , tr and olapril , 2 mg once daily , is effective in reducing blood pressure . Its efficacy over 24 h is better documented by 24-h blood pressure monitoring than by isolated clinic blood pressure measurement Objective To compare the effects of a calcium antagonist ( nitrendipine ) and an angiotensin converting enzyme inhibitor ( enalapril ) with those of placebo on left ventricular mass in patients with non-insulin-dependent diabetes mellitus and hypertension . Design A double-blind r and omized , placebo-controlled trial . Setting General practitioners referred patients to the trial physician . Patients The study population comprised 121 patients with non-insulin-dependent diabetes mellitus . Inclusion criteria for blood pressure were diastolic blood pressure 90–115 mmHg and systolic blood pressure ⩽ 200 mmHg , while subjects were not being administered blood-pressure-lowering drugs for 3 weeks . Intervention Patients were r and omly allocated to receive nitrendipine ( n = 40 ) , enalapril ( n = 40 ) or placebo ( n = 41 ) . The treatment period was 48 weeks . Main outcome measures The effect of nitrendipine was defined as the difference in change in left ventricular mass index from baseline between nitrendipine treatment and placebo after 48 weeks of treatment . The effects of nitrendipine compared with that of enalapril and of enalapril compared with placebo were defined similarly . Left ventricular mass was measured by M-mode echocardiography . Results Use of nitrendipine and enalapril led to significant and almost identical reductions in systolic and diastolic blood pressures . During 48 weeks left ventricular mass index decreased by 5 % for patients in the nitrendipine group ( decrease by 12 g/m2 , 95 % confidence interval 1–23 ) , remained about the same for patients in the enalapril group ( decrease by 1 g/m2 , 95 % confidence interval decrease by 10 to increase by 9 ) and increased by 9 % for patients in the placebo group ( increase by 9 g/m2 , 95 % confidence interval 2–16 ) . Conclusion These results indicate that administration of nitrendipine to patients with non-insulin-dependent diabetes mellitus and hypertension  reduces left ventricular mass index . Enalapril appears not to induce regression , but perhaps prevents progression with an effect that is intermediate between those of nitrendipine and placebo . J Hypertens 16:689–696 © 1998 Lippincott-Raven Publishers We have previously shown that enalapril , when given acutely to renovascular patients , exerted a dose-dependent hypotensive effect . To address the same problem in chronically treated essential hypertensives , we studied 116 uncomplicated essential hypertensives , whose diastolic blood pressure was greater than or equal to 95 mm Hg at the end of a two-week placebo run-in period ( time 0 ) . According to a r and omized crossover design , these patients received three doses ( 10 , 20 , or 40 mg ) of enalapril qd and a placebo , each treatment being given for one month . At the end of each treatment period as well as at time 0 , blood pressure and heart rate were measured 24 hours after the last dosing . In spite of a two-week run-in placebo period , placebo treatment further and significantly reduced blood pressure ; however enalapril further and significantly reduced blood pressure when compared to placebo . Although absolute blood pressure values after 40 mg of enalapril were significantly lower than those after 10 mg of enalapril the relevance of this difference , mainly when compared to placebo , seems to be inconsistent . Taken together these data suggest that the hypotensive effect of enalapril chronically given to essential hypertensives and measured 24 hours after last dosing , is dose independent In a r and omized , double-blind trial , 2 doses of ramipril ( 2.5 and 5 mg once daily ) were compared with placebo in patients with mild to moderate essential hypertension . A 2-week placebo run-in phase was followed by 4 weeks of treatment . Eighty-six patients entered the study and 17 withdrew during the course of the study . Both doses of ramipril appeared to be more effective than placebo in reducing blood pressure , but significant differences between 2.5 mg of ramipril and placebo were not found in any statistical analyses . In the endpoint analyses ( taking the last measurement from each patient ) , the patients receiving 5 mg of ramipril had significantly larger decreases in blood pressure than the patients receiving placebo ( t tests : st and ing systolic , p less than 0.001 ; supine diastolic , p less than 0.05 ; st and ing diastolic , p less than 0.05 ) and also than the patients receiving 2.5 mg of ramipril ( st and ing systolic , p less than 0.05 ) . It appears from the results of this study that the minimum effective dosage of ramipril is 5 mg once daily . No clinical ly relevant side effects or clinical ly relevant changes in laboratory values were observed The effects of the ACE inhibitor spirapril and of hydrochlorothiazide on left ventricular diastolic function were studied . Thirteen patients with mild to moderate essential hypertension completed this r and omized , double-blinded , placebo-controlled , crossover study . After a three-week run-in period the patients entered three periods lasting four weeks each , wherein they were treated with placebo , spirapril , or hydrochlorothiazide .  Blood pressure , hemodynamic variables ( stroke volume , heart rate , cardiac output , index of contractility , and systemic vascular resistance ) , echocardiography ( left ventricular mass ) , and Doppler-derived atrial to early (A/E)-ratio velocity time integrals ( VTI ) were measured at the end of each of the four periods . Spirapril lowered the A/E-ratio VTIs ( 0.57 , 0.12 - 1.00 ) ( P < 0.02 ) as compared with both placebo ( 0.80 , 0.50 - 2.67 ) and hydrochlorothiazide ( 0.83 , 0.44 - 1.25 ) , and the drug normalized the A/E-ratio VTI in those patients with elevated values . The hemodynamic variables , left ventricular mass , and end-systolic wall stress were unchanged during all three treatments . There were no significant changes in mean blood pressure during the treatment periods . These results indicate that spirapril lowers A/E ratio within four weeks in patients with mild to moderate essential hypertension . It thereby seems able to improve left ventricular diastolic function . The effect is not dependent upon changes in hemodynamic variables , blood pressure , left ventricular mass , or end-systolic wall stress BACKGROUND The excess morning risk of myocardial infa rct ion and stroke may be attributable to the rapid rise in blood pressure ( BP ) and heart rate in the hours after awakening . The aim of this r and omized , double-blinded , placebo-controlled , multicenter study was to compare once-daily , controlled-onset , extended-release ( COER-24 ) verapamil to enalapril and losartan on BP and heart rate during the postawakening morning phase as well as throughout the 24-h period . METHODS A total of 406 patients were r and omized to an 8-week forced-titration period with one of the following : 1 ) COER-24 verapamil 240 mg/day titrated to 360 mg/day ; 2 ) enalapril 10 mg/day titrated to 20 mg/day , 3 ) losartan 50 mg/day titrated to 100 mg/day , or 4 ) placebo .  Office BP and heart rate and ambulatory 24-h BP monitoring was performed at baseline , 4 weeks , and 8 weeks . RESULTS Each active treatment , as compared with placebo , lowered BP both during the morning hours as well as the entire 24-h period . COER-24 verapamil was more effective in lowering morning systolic ( -16.6 mm Hg ) and diastolic ( -11.9 mm Hg ) BP than either enalapril or losartan ( P < .001 ) . For the entire 24-h period , the effects of COER-24 verapamil ( -11.6/-8.4 mm Hg ) were comparable to enalapril ( - 13.4/-8.3 mm Hg ; P = NS ) . Losartan achieved a similar 24-h effect on systolic pressure ( -9.3 mm Hg ) but was less effective on diastolic pressure ( -5.4 mm Hg ; P = .004 v COER-verapamil ) . Unlike losartan or enalapril , COER-24 verapamil was the only treatment to lower the heart rate over both the 24-h period ( -4.6 beats/min ; P < .001 ) and during waking hours ( -4.6 beats/min ; P < .001 ) . A blunted rate of rise in BP , heart rate , and rate-pressure product occurred during the postawakening period with COER-verapamil ( P = .03 ) but not with either of the other treatment arms . Lastly , the decline in BP at night was similar for COER-verapamil and losartan and greater with enalapril ( P = .014 ) CONCLUSIONS COER-24 verapamil produces changes in BP and pulse that more closely match the normal circadian hemodynamic rhythms than either do enalapril or losartan OBJECTIVE To assess the efficacy and safety of several combinations of benazepril , an angiotensin-converting enzyme inhibitor , and hydrochlorothiazide , as compared with placebo , in the treatment of patients with essential hypertension . DESIGN A 6-week , r and omized , double-blind , parallel study conducted at 24 centers . A placebo run-in period of 1 to 4 weeks preceded the double-blind phase . PARTICIPANTS AND SETTING Male and female out patients , aged 18 years and older , were eligible to participate if their sitting diastolic blood pressure was between 95 and 114 mm Hg at the last two consecutive visits during the placebo phase . Among the 334 patients who entered the double-blind phase , 17 % were aged 65 years or older and 26 % were black . Eleven patients withdrew because of adverse experiences , including two patients receiving placebo . INTERVENTIONS Patients received placebo ; benazepril , 20 mg ; hydrochlorothiazide , 25 mg ; or combination therapy with benazepril/hydrochlorothiazide , 5/6.25 mg , 10/12.5 mg , 20/25 mg , 20/6.25 mg , or 5/25 mg , once daily for 6 weeks . MAIN OUTCOME MEASURES The mean change from baseline in sitting diastolic blood pressure at end point ( last postr and omization measurement carried forward ) in the double-blind phase . Combination therapy with benazepril/hydrochlorothiazide , 20/25 mg , was compared with benazepril , 20 mg alone , and hydrochlorothiazide , 25 mg alone . Sitting systolic blood pressure and the effect of race and age on treatment efficacy were also evaluated . RESULTS Compared with placebo , all benazepril/hydrochlorothiazide combinations produced statistically significant reductions from baseline in sitting diastolic and systolic blood pressures at study end point . In the benazepril/hydrochlorothiazide , 20/25 mg , group , the adjusted mean changes in sitting diastolic blood pressure at end point were statistically significantly greater than those in the monotherapy treatment groups ( benazepril , 20 mg , P < or = .05 ; hydrochlorothiazide , 25 mg , P < or = .001 ) alone . All therapies were generally well tolerated . Decreases in mean serum potassium level with hydrochlorothiazide monotherapy were reduced or eliminated with combination therapy . CONCLUSION Benazepril in combination with hydrochlorothiazide , including a low-dose combination of 5/6.25 mg , is effective in reducing sitting diastolic and systolic blood pressure in patients with hypertension A multicenter , double-blind , r and omized , and placebo-controlled trial , the Perindopril Therapeutic Safety Study ( PUTS ) , was design ed to assess the interaction between angiotensin-converting enzyme ( ACE ) inhibition and the diseases and therapies commonly found associated with mild hypertension . A total of 480 male and female patients aged 30 - 70 years with a diastolic pressure of 90 - 104 mm Hg were included after a 3-week placebo run-in if they satisfied st and ard criteria for any of the following : hyperlipidemia , type II diabetes , ischemic heart disease , cardiac arrhythmia , peripheral arterial occlusive disease , nephropathy with proteinuria , chronic obstructive lung disease or treatment with nonsteroidal anti-inflammatory drugs ( NSAIDs ) . At the end of the placebo run-in period , patients were r and omly assigned to either placebo or perindopril 4 mg once daily . A total of 460 patients completed the 6-week double-blind phase , comprising 3 assessment s at 1 , 3 , and 6 weeks . In this report , the principal results obtained in 5 disease groups ( hyperlipidemia , type II diabetes , ischemic heart disease , nephropathy with proteinuria , and NSAID treatment ) will be reported . A total of 269 patients belonging to one of the aforementioned 5 disease groups completed the double-blind phase of the study and were included for statistical evaluation . In the perindopril group , systolic and diastolic blood pressures decreased significantly more than in the placebo group , and a sitting diastolic blood pressure of 90 mm Hg was achieved in 65 % of patients in the perindopril group and 30 % of patients in the placebo group . The incidence of symptoms spontaneously reported by the patients was low : 2 patients of the perindopril group complained of cough . ( ABSTRACT TRUNCATED AT 250 WORDS Objective To evaluate the efficacy and duration of action of the angiotensin converting enzyme inhibitor quinapril hydrochloride by using ambulatory blood pressure monitoring . Design Eleven centers in the USA and Canada entered 155 patients with previously diagnosed hypertension into a 4-week placebo-baseline phase . Twenty patients ( 13 % ) with elevated diastolic blood pressure ( DBP ) only by cuff measurement were excluded from entry into a double-blind test based on ambulatory blood pressure monitoring , and 135 patients with a mean waking blood pressure of 155/100 mmHg were assigned r and omly to receive either quinapril or placebo once a day for 8 weeks , with optional titration to a higher dose after 4 weeks , based on the DBP response assessed by repeat ambulatory blood pressure monitoring only . Results Quinapril therapy produced highly significant decrease in mean daytime DBP compared with placebo . The antihypertensive effect of quinapril was evident over 24 h , with 50 % of the peak effect remaining at the trough . After 4 weeks of treatment 49 % of the patients in the quinapril group were titrated to the higher dose compared with 86 % of the patients who had been receiving placebo . More than 70 % of the patients in the quinapril group who remained at the low dose would have been titrated to the higher dose based solely on the clinic DBP measurements . Conclusions The use of ambulatory blood pressure monitoring in the present study reduced the false-positive response to placebo and lessened the likelihood of titrating patients to the higher dose of quinapril in comparison with the number that would have been so treated based on clinic blood pressure measurements alone . More importantly , our results suggest that the convenience , ease and relatively low cost of traditional cuff blood pressure measurement should be weighed against the potential shortcomings of the method OBJECTIVE : To compare the effects on office blood pressure and home blood pressure of placebo and active drug administration . DESIGN : After a 2-week wash-out period , patients with mild-to-moderate hypertension entered a 2-week single-blind placebo period and then a 4-week double-blind period . Patients were r and omly assigned to be administered either 2 mg tr and olapril once daily or its placebo in a 2:1 proportion . Office blood pressure was measured by a physician at the end of each period , using a mercury sphygmomanometer ( mean of three consecutive measurements ) . Home blood pressure was measured during the last week of each period according to st and ard procedure carefully taught to each patient by the physician . Compliance was checked by using electronic pill boxes . RESULTS : Data for 34 of the 44 patients who entered the study were eligible for analysis .  Baseline systolic blood pressure/diastolic blood pressure were significantly ( P = 0.0001/P = 0.0001 ) higher for office blood pressure ( 161/101 mmHg ) than they were for home blood pressure ( 145/93 mmHg ) . There was no statistically significant difference between the placebo and active-treatment groups at baseline . During the single-blind period , blood pressures measured at the office and at home did not change significantly . Office blood pressure decreased by 2.7 + /- 10 mmHg for systolic blood pressure and by 0.5 + /- 4 mmHg for diastolic blood pressure whereas home blood pressure increased by 0.8 + /- 6 mmHg for systolic blood pressure and by 0.7 + /- 4 mmHg for diastolic blood pressure . During the double-blind period , office blood pressure fell significantly with tr and olapril treatment ( systolic by 10.2 + /- 12 mmHg , diastolic by 8.3 + /- 6 mmHg ; P = 0.0005/0.0001 , versus single-blind placebo period ) but this decrease was not significantly different ( P = 0.45/0.92 ) from the fall in members of the placebo group ( systolic by 6.9 + /- 9 mmHg , diastolic by 8.0 + /-6 mmHg ; P = 0.04/0.002 , versus single-blind placebo period ) . Thus , no antihypertensive effect of tr and olapril was demonstrated . The fall lin home blood pressure with tr and olapril treatment was significant ( systolic by 10.7 + /- 8 mmHg , diastolic by 5.8 + /- 5 mmHg ; both P = 0.0001 , versus single-blind placebo period ) and was significantly greater ( P = 0.0004/0.004 ) than the minimal change observed with placebo ( systolic fell by 0.2 + /- 5mmHg , diastolic fell by 0.6 + /- 4 mmHg ; P = 0.90/0.62 , respectively , versus single-blind placebo period ) . The evening decrease in home blood pressure was similar to the morning decrease in home blood pressure in members of the tr and olapril-treated group . The result ing morning : evening decrease in blood pressure ratio was 0.83 for diastolic blood pressure and 0.95 for systolic blood pressure . For the subgroup of responders , mean of individual ratios was 0.77 + /- 0.43 for diastolic blood pressure and 0.70 + /- 0.39 for systolic blood pressure . CONCLUSION : The placebo effect observed with office blood pressure measurements does not occur with home blood pressure measurements . Expected treatment effect can alter a physician 's blood pressure readings . The precision of measurements is greater with home blood pressure ( there is a lower SD ) . Use of home blood pressure measurements increases the power of comparative trials , allowing one either to study fewer subjects or to detect a smaller difference in blood pressure Objective To compare the effect of captopril with that of placebo on peripheral and hepatic insulin action in essential hypertension , in light of evidence that insulin resistance is associated with cardiovascular risk . Design R and omized , double-blind , placebo-controlled , crossover trial , with 8 week treatment periods of captopril and placebo preceded and separated by 6 weeks of placebo . Setting Belfast teaching hospital . Patients Eighteen Caucasian nondiabetic patients ( 10 males ) , aged under 65 years , with essential hypertension , recruited from general practice s in the greater Belfast area . Interventions Captopril at 50 mg twice a day or placebo twice a day for two 8 week treatment periods . Main outcome measures Peripheral and hepatic insulin sensitivity assessed by glucose clamps . Results Fourteen patients completed the study . Mean ( ± SEM ) levels of fasting glucose , fasting insulin and postabsorptive hepatic glucose production were similar after captopril and placebo ( 5.4 ± 0.1 versus 5.4 ± 0.1 mmol/l , 10.6 ± 2.2 versus 9.5 ± 1.1 mU/l , 11.2 ± 0.6 versus 11.0 ± 0.5 mmol/kg per min , respectively ) . During hyperinsulinaemia , hepatic glucose production was suppressed to comparable levels after both treatments ( 4.8 ± 0.6 versus 4.3 ± 0.6 mmol/kg per min ) and exogenous glucose infusion rates required to maintain euglycaemia were also similar ( 30.0 ± 2.6 versus 30.3 ± 2.6 mmol/kg per min ) . Conclusion Captopril therapy in uncomplicated essential hypertension has no effect on peripheral or hepatic insulin sensitivity A multicenter , double-blind , placebo-controlled trial with multifactorial design was conducted to evaluate the safety and efficacy of the calcium-channel blocker diltiazem , in a sustained release preparation , and the angiotensin converting enzyme inhibitor , lisinopril , in the treatment of elderly Chinese patients with mild-to-moderate hypertension . In addition to the hypotensive effects of combinations of both drugs compared with monotherapy , all given once daily , the effect on quality of life was also evaluated . This study consisted of a 3 x 2 multifactorial design in which 156 women and men with a sitting diastolic pressure of between 95 mm Hg and 114 mm Hg , after a 4-week placebo washout phase , were r and omized to one of six treatment groups for 12 weeks of active treatment . Monotherapy with diltiazem 120 or 240 mg produced increasing reductions of systolic and diastolic blood pressure . Compared with placebo , lisinopril 10 mg had an effect intermediate between the diltiazem doses . The combinations of diltiazem 240 mg + lisinopril 10 mg and diltiazem 120 mg + lisinopril 10 mg showed increased efficacy in reducing systolic and diastolic blood pressure compared to these drug doses used in monotherapy , but the effect of the combinations was less than predicted by an additive model . Although the total number of other adverse events reported was similar for all active treatment groups compared to placebo , lisinopril-induced cough was common with an incidence of 31 % after rechallenge . Premature drug withdrawal was necessary in four of 78 patients receiving lisinopril , due to intractable cough . The combination of diltiazem 240 mg and lisinopril 10 mg was significantly more effective at reducing blood pressure than either drug alone ; this additive effect did not result in a higher rate of adverse effects or impairment of quality of life . Thus , combination therapy with these agents was well tolerated and result ed in increased efficacy in these elderly patients This r and omized , double-blind , double-dummy , placebo-controlled , parallel-group study evaluated the dose-response relationship of telmisartan in 207 patients with mild to moderate hypertension ( diastolic blood pressure [ DBP ] 100 to 114 mmHg ) . After a 28-day placebo run-in period , patients were r and omized to 28 days of once-daily , double-blind , double-dummy treatment with telmisartan 40 , 80 , or 120 mg ; enalapril 20 mg ; or placebo .  Blood pressure ( BP ) was manually recorded for 12 hours after the first dose and after 24 hours at baseline ( Day 0 ) , Day 1 , and Day 28 of double-blind treatment . Pharmacokinetic and pharmacodynamic parameters were assessed from telmisartan plasma concentrations . All doses of telmisartan and enalapril significantly reduced BP compared with placebo ( p < or = 0.01 ) . Mean + /- SE reductions in supine DBP after 28 days of treatment ranged between 7.9 + /- 1.3 mmHg and 9.8 + /- 1.3 mmHg in the telmisartan groups , 9.6 + /- 1.3 mmHg with enalapril , and 1.5 + /- 1.3 mmHg with placebo . Mean + /- SE reductions in supine systolic blood pressure ( SBP ) were between 10.0 + /- 2.2 mmHg and 15.5 + /- 2.2 mmHg with telmisartan versus 10.2 + /- 2.1 mmHg with enalapril ; placebo increased supine SBP by 3.5 + /- 2.1 mmHg . The BP reductions after 4 weeks of treatment with telmisartan were no different from those achieved with enalapril . No significant linear trend in BP reduction was evident among telmisartan doses . Reductions in SBP and DBP were maintained over the 24-hour period at Day 28 . Treatment did not affect supine heart rate . Trough/peak DBP ratios were > or = 85 % for all telmisartan doses versus 65 % for enalapril . High interpatient variability in  telmisartan plasma concentrations was observed . For example , mean + /- SD values for Cmax were 159 + /- 104 ng/mL for telmisartan 40 mg , 693 + /- 606 ng/mL for telmisartan 80 mg , and 1635 + /- 1406 ng/mL for telmisartan 120 mg . Plasma concentration-effect analyses indicated that the antihypertensive effects of telmisartan 40 , 80 , and 120 mg are at the plateau region of the concentration-response curve . All active treatments were well tolerated , with tolerability profiles similar to placebo , and telmisartan did not produce any clinical ly relevant first-dose effects . These data confirm the antihypertensive efficacy and placebo-like tolerability of telmisartan The efficacy and safety of various doses of losartan potassium , a specific and selective angiotensin II receptor antagonist , were compared with those of placebo and enalapril maleate 20 mg in patients with mild to moderate essential hypertension in a r and omized , double-blind , parallel study . We r and omly allocated 576 patients at the end of a 4-week placebo baseline period to 8 weeks of once-daily double-blind treatment with losartan potassium 10 , 25 , 50 , 100 , or 150 mg , enalapril maleate 20 mg , or placebo . After 8 weeks of treatment , mean reductions from baseline in supine systolic/diastolic pressure 24 hours after dosing ( trough ) for losartan potassium 10 , 25 , 50 , 100 , and 150 mg , enalapril maleate 20 mg , and placebo were 7.6/7.9 , 7.8/6.8 , 13.0/10.1 , 8.9/9.9 , 10.5/9.7 , 14.7/11.2 , and 3.8/5.6 mm Hg , respectively . Compared with mean changes in supine diastolic pressure in the placebo group , losartan potassium 50 to 150 mg and enalapril maleate 20 mg produced clinical ly important and statistically significant reductions ( P < or = .01 ) in blood pressure . At 24 hours after dosing , the blood pressure changes obtained with losartan potassium 50 mg were essentially identical to those obtained with enalapril maleate 20 mg . While there was a dose-related effect with losartan potassium from 10 to 50 mg at peak ( 6 hours after dosing ) , doses of 10 and 25 mg were not consistently different from placebo 24 hours after dosing . To assess the once-daily effect of losartan potassium , trough-to-peak ratios of the mean changes in supine diastolic pressure after 8 weeks of treatment were calculated . ( ABSTRACT TRUNCATED AT 250 WORDS The dose-response relationship of ramipril was examined in 216 subjects with mild-to-moderate essential hypertension in a double-blind , placebo-controlled , multicenter study . Ramipril capsules ( 1.25 , 2.5 , 5 , or 10 mg ) or placebo capsules were administered once daily for 12 weeks . Significant reductions in supine and st and ing diastolic and systolic blood pressures were seen at end point in the ramipril 2.5 , 5 , and 10 mg treatment groups compared with placebo . The antihypertensive effect was greater at higher doses . The minimum effective dose of ramipril was 2.5 mg once daily Quinapril HCl is a novel , nonsulf hydryl angiotensin-converting en zyme ( ACE ) inhibitor . The Study Group evaluated its efficacy ( 20 , 40 , 80 mg daily with forced dose titration determination at trough blood pres sure ) once daily versus twice daily versus placebo , as well as its tolera bility and safety , in 270 patients with mild to moderate essential hyperten sion ( WHO Stages I and II , sitting diastolic blood pressure [ DPB ] ≥95 mm Hg ) , for twelve weeks . Reduc tions in DBP of up to 13 mm Hg were obtained , and in full dosage more than 65 % of patients achieved a re duction in DBP of 10 mm Hg or more from baseline or reduced their DBP to 90 mm Hg or less  . Quinapril was well tolerated , and reported adverse effects were scarcely more frequent than in the placebo group . Once daily doses of quinapril were as safe and effective as twice-daily doses . Quina pril is likely to exhibit good therapeu tic utility in the management of essential hypertension PURPOSE Many hypertensive patients have other , usually long-term diseases . Antihypertensive therapy may interfere with these diseases and their therapies . In the present study , the possible interactions of the ACE-inhibitor perindopril with several of the most common long-term diseases was evaluated . PATIENTS AND METHODS In a multicenter , double-blind , r and omized , placebo-controlled trial , the effect of perindopril was evaluated in 490 patients with mild essential hypertension and any one of the following concomitant diseases : hyperlipidemia , type II diabetes mellitus , ischemic heart disease , cardiac arrhythmia , peripheral arterial occlusive disease , nephropathy with proteinuria , chronic obstructive pulmonary disease , or degenerative joint disease treated with nonsteroidal anti-inflammatory drugs ( NSAIDs ) . After a 3-week single-blind placebo run-in , the patients received either perindopril ( 4 mg/d ) or matching placebo for 6 weeks . RESULTS Blood pressure was effectively reduced by perindopril irrespective of the associated disease . The rate of spontaneously reported side effects was low . Treatment with perindopril was free from adverse interactions with the concomitant diseases and therapies . Moreover , favorable actions could be observed in patients with ischemic heart disease ( reduction of maximal ST-segment depression during peak exercise and decrease in the number of angina attacks ) , in patients with proteinuria ( decrease in albuminuria in patients with normal serum creatinine levels ) , and in patients with NSAID-treatment ( increase in prostagl and in E2 concentration in gastric mucosa suggesting gastric cytoprotection ) . CONCLUSION This trial shows that ACE-inhibition with perindopril represents a simple , safe , and effective short-term therapeutic option for the large proportion of patients with mild essential hypertension and concomitant diseases and therapies Hypertension is an important cardiovascular risk factor and the goal of its pharmacologic treatment is to reduce morbidity and mortality . Treatment is usually initiated with a low dose of a single agent and titrated to a higher dose as required . As many as 50 % of patients require the addition of a second agent to achieve satisfactory blood pressure control . The aim of this study was to assess the dose-response relationship of nitrendipine and enalapril alone or in fixed combination in the treatment of mild to moderate hypertension . A total of 496 patients were enrolled in a multicenter , r and omized , double-blind , factorial- design , parallel-group clinical trial comparing placebo , nitrendipine ( 5 , 10 , and 20 mg ) and enalapril ( 5 , 10 , and 20 mg ) alone or in combination . After a single-blind , 2-week placebo run-in period , 414 patients whose diastolic blood pressure ranged between 90–109 mm Hg were r and omly assigned to a treatment group . The combination of nitrendipine and enalapril , particularly regimens including nitrendipine 20 mg and enalapril 5 or 10 mg , were significantly superior to both monotherapies ; mean diastolic blood pressure reductions from baseline to last visit were −12.5 and −14.3 mm Hg , respectively . Response surface analysis provided further evidence that these combinations were optimal in terms of anti-hypertensive efficacy . All treatments were well tolerated and the incidence of adverse events did not differ significantly between groups . In summary , the anti-hypertensive efficacy of the combination was found to be superior to both monotherapies at any doses . The dose combination achieving the greatest blood pressure reduction was nitrendipine 20 mg and enalapril 10 mg This multicenter , double-masked , r and omized , parallel-group study compared the efficacy , tolerability , and safety of amlodipine 5 mg/benazepril 20 mg , amlodipine 5 mg , benazepril 20 mg , and placebo in patients with essential hypertension . After a placebo run-in period , 308 patients ( all white ) were r and omized to treatment groups and took medication once daily for 8 weeks . Blood pressure was measured after 4 and 8 weeks of treatment in the 23- to 26-hour period after dosing . Patients wore a noninvasive blood pressure monitor  for 24 hours before r and omization and before the final visit . Investigators recorded adverse experiences at r and omization and at study weeks 4 and 8 , and obtained specimens for laboratory testing at r and omization and at study week 8 . Three hundred seven patients were evaluated for efficacy , and 308 for tolerability and safety . At end point ( the last postr and omization measurement for each patient ) , the reduction in mean sitting diastolic blood pressure with the amlodipine 5 mg/benazepril 20 mg treatment was statistically significantly greater than with any comparative therapy . The results of 24-hour monitoring showed that the amlodipine/benazepril treatment , unlike monotherapy , maintained the hourly mean diastolic blood pressure at < or = 90 mm Hg . A responder rate of 87.0 % was observed with amlodipine 5 mg/benazepril 20 mg versus 67.5 % , 53.3 % , and 15.8 % with amlodipine , benazepril , and placebo , respectively . This difference between the amlodipine/benazepril treatment group and each comparative single-agent treatment group was statistically significant . Drug-related adverse events occurred in 15.6 % of patients in the amlodipine/benazepril group and in 24.7 % , 6.5 % , and 11.7 % of patients in the amlodipine , benazepril , and placebo groups , respectively . Edema occurred less often in the amlodipine/benazepril group than in the amlodipine group . Overall , once-daily therapy with amlodipine 5 mg/benazepril 20 mg provided an antihypertensive effect that was statistically and clinical ly superior to amlodipine 5 mg alone , benazepril 20 mg alone , and placebo , was well tolerated , and was associated with less edema than the amlodipine treatment The new angiotensin converting enzyme inhibitor , enalapril ( MK-421 ) , was tested by a double-blind trial . Patients with uncomplicated essential hypertension were r and omly allocated to one of two stepped-care treatment groups : enalapril 20 mg once-a-day , or placebo as the first step , followed when necessary by the successive addition of hydrochlorothiazide ( 25 and 50 mg ) , oxprenolol ( 160 and 320 mg ) and dihydralazine ( 50 and 100 mg ) . Blood pressure was normalized in both groups , although the enalapril group showed lower systolic and diastolic blood pressures than the placebo group ( systolic 130.5 + /- 12 versus 136.6 + /- 9 mmHg , P less than 0.01 ; diastolic 82.8 + /- 6 versus 87.0 + /- 5 mmHg , P less than 0.001 ) . These results were obtained with a smaller number of tablets per day ( 2.6 + /- 1.8 versus 4.2 + /- 2.4 mmHg , P less than 0.0001 ) . Plasma potassium was identical for both groups at the start of treatment . At the end of the study , it was significantly higher in the enalapril group than in the placebo group ( 4.1 + /- 0.3 versus 3.9 + /- 0.5 mmol/l ; P less than 0.05 ) . Spontaneous complaints were noted during the bi-weekly or monthly visit and were also expressed by patients completing a self-administered question naire . Differences in spontaneous complaints or in the symptoms evaluated by the question naire were not significant . The increase in the number of symptoms at the end of the study was greater in the placebo group than in the enalapril group , but the difference was not statistically significant . ( ABSTRACT TRUNCATED AT 250 WORDS The dose-response relationship of enalapril was evaluated in a double-blind , balanced , two-period , incomplete-block study in 91 patients with mild to moderate essential hypertension . Patients were r and omly assigned to two of six treatments : placebo , 2.5 , 5 , 10 , 20 and 40 mg/day of enalapril maleate . There were two 3-week treatment periods , each preceded by a 4-week , single-blind placebo washout . Each dose of enalapril produced significant decreases in st and ing and supine systolic and diastolic blood pressure after 2 and 3 weeks of treatment . There were no significant changes on placebo . There was a significant linear dose response relationship for both mean blood pressure and mean change from baseline in blood pressure ( P less than 0.01 for systolic and mean arterial pressure , and P less than 0.05 for diastolic pressure ) . Enalapril was associated with an increasing dose-response relationship across the 2.5 - 40 mg/day range . The 2.5 mg/dose is effective in some patients ; however , doses greater than or equal to 10 mg/day may be necessary to achieve satisfactory blood pressure control Summary : The effect of the angiotensin-converting enzyme (ACE)-inhibitor perindopril on serum lipids and apolipoprotein concentrations were assessed in a multicenter , r and omized , double-blind , placebo-controlled study in 51 hyperlipidemic patients treated for mild hypertension .  Perindopril was given as a single morning dose ( 4 mg ) for 6 weeks . During the treatment period , blood pressure ( BP ) was significantly ( p < 0.001 ) reduced from 159/99 to 148/90 mm Hg by verum treatment and from 158/101 to 151/95 mm Hg ( NS ) by placebo treatment . Neither total cholesterol and triglycerides nor high-density-lipoprotein and apolipoprotein AI and B levels were significantly altered by drug treatment as compared with placebo . Although perindopril had good antihypertensive effect in patients with mild hypertension and hyperlipidemia , it had no adverse effects on lipid metabolism in these patients . Therefore , perindopril is recommended for antihypertensive treatment , especially in hypertensive patients with concomitant hyperlipidemia Short-term results of this double-blind control trial ( previously reported ) in patients with initial diastolic blood pressures ( DBP ) in the range of 92 - 109 mm Hg indicated that doses of 12.5 or 25 mg captopril ( C )  three times daily ( t.i.d . ) and 37.5 mg twice daily ( b.i.d . ) had similar antihypertensive effectiveness as 50 mg t.i.d . After 7 weeks of C , the addition of hydrochlorothiazide ( H ) to two-thirds of the patients enhanced the antihypertensive response . This report presents the results of unchanged and uninterrupted treatment for 9.5 months in 46 patients taking C alone , and for 7.8 months in 94 patients taking C plus H or H alone .  With C alone , reductions in DBP averaged 8.3 , 11.0 , 15.1 , and 17.5 mm Hg with the 12.5 , 25 , 37.5 , and 50 mg doses respectively . The response to the 12.5 mg dose only was significantly less than the 50 mg dose . With H alone , the reduction in DBP averaged 10.6 mm Hg and with C plus H reductions averaged 15.6 , 18.1 , 16.8 , and 18.7 mm Hg with the 12.5 , 25 , 37.5 , and 50 mg doses of C , respectively . Reductions in DBP with C plus H regimens were significantly different from H alone . There was no waning of effectiveness from short to long term except for the 12.5 mg dose of C alone . During the long-term phase , two patients developed rash and one lost the sense of taste . Neutropenia in one patient probably was not drug-related . There were no terminations for elevated DBP greater than 104 mm Hg on two successive visits . ( ABSTRACT TRUNCATED AT 250 WORDS To test the dose responses of piretanide , ramipril , and their combination in patients with essential hypertension , a prospect i ve , r and omized , double-blind , placebo-controlled trial was conducted in 480 patients . Twelve separate groups were studied : placebo , piretanide 3 mg , piretanide 6 mg , ramipril 2.5 mg , ramipril 5 mg , ramipril 10 mg , and their combinations , as single daily morning doses . Patients were r and omized after a 2-week run-in period without drugs ; treatment was given for 6 weeks . A dose response compared with placebo was found for both drugs ; the combination was more effective than either drug alone . Piretanide 6 mg , combined with ramipril 5 mg , provided optimal blood pressure reduction . Self-reported adverse effects of both drugs and their combinations did not exceed those reported for placebo . A surface analysis suggested that piretanide primarily reduced systolic blood pressure , whereas ramipril was more effective in reducing diastolic blood pressure . The data attest to a combined efficacy of piretanide and ramipril in decreasing arterial blood pressure OBJECTIVE To evaluate the antihypertensive effects of cilazapril , a new angiotensin-converting enzyme inhibitor , on clinic and ambulatory blood pressure ( ABP ) after first and last dose administrations . DESIGN Four weeks r and omized , double-blind , controlled trial of three regimens . SETTING Six hypertensive research clinics in Canada . PATIENTS After a two-week placebo run-in period , 130 patients aged 22 to 77 years with mild to moderate essential hypertension were r and omized and evaluated . Exclusion criteria were secondary hypertension , childbearing potential and other significant diseases . INTERVENTION Patients were assigned to cilazapril 2.5 mg ( 44 patients ) , cilazapril 5 mg ( 42 ) or placebo ( 44 ) . Fourteen patients in each group were further evaluated in a sub study by 24 h ABP monitoring . MAIN RESULTS Cilazapril in either dosage induced significant and similar antihypertensive effects on clinic blood pressure shortly after dosing ( 2 to 4 h ) , persisting during chronic treatment ; however , no relevant effect persisted at the end of dosing ( 24 h ) . After four weeks , at the end of dosing , 22 , 24 and 38 % of patients were clinical responders ( decrease in sitting diastolic blood pressure 10 mmHg or greater ) on placebo , 2.5 or 5 mg ( differences not significant ) . Conversely , both cilazapril regimens induced similar and significant ( P < 0.01 ) falls in mean 24 h ABP compared with placebo . Moreover , 7 , 50 and 48 % of patients exhibited a reduction in mean 24 h diastolic blood pressure 10 mmHg or greater on placebo , cilazapril 2.5 or 5 mg , respectively . Furthermore , both regimens induced adequate trough : peak ratios on ABP 1 . This was a multicentre , double-blind , parallel study in 216 patients with mild to moderate ( supine diastolic blood pressure = 95 - 115 mm Hg ) essential hypertension . 2 . After a 4-week placebo washout , patients were r and omized to placebo or lisinopril 1.25 , 5.20 or 80 mg once daily for 6 consecutive weeks . Supine and erect blood pressure was measured 24 h postdose at the end of weeks -2 , 0 , 2 , 4 , and 6 . 3 . There was a linear dose-response relationship for both supine and erect blood pressure . Diastolic blood pressure reductions in the lisinopril 20 and 80 mg day-1 groups were significantly greater than in the placebo or lisinopril 1.25 and 5 mg day-1 groups . 4 . Lisinopril , at doses up to 80 mg day-1 , was well tolerated The antihypertensive efficacy of N‐[(S)‐I‐(ethoxycarbonyl)‐3‐phenyl‐propyl]‐L‐alanyl‐L‐proline ( enalapril maleate ) was evaluated in a r and omized , double‐blind trial in 23 patients with mild low‐renin essential hypertension ranging in age from 32 to 70 yr ( 20 were black and 3 were white ) . All underwent a 4‐wk washout‐placebo phase and were then assigned to a dosing schedule of either 10 mg enalapril once daily , 5 mg enalapril twice daily , or placebo twice daily for 12 wk . Conditional on diastolic pressure , the dose was increased at 4‐wk intervals to a maximum of 40 mg daily or until control was achieved or the end of the study reached . At the end of the 12‐wk titration phase , there was a follow‐up period during which measurements were made after discontinuation of the medication . Mean supine diastolic pressure decreased from baseline ( 98.5 ± 2.6 mm Hg ) during the titration phase ( 86.3 ± 4.6 mm Hg ) in the group taking enalapril once daily . In three of the eight patients in the once‐daily group and five of eight in the twice‐daily group , supine diastolic pressures fell below 90 mm Hg . Neither supine nor st and ing systolic pressure nor st and ing diastolic pressure decreased significantly from pretreatment levels during enalapril once or twice daily . Heart rates measured after 5 min supine rest were not altered by enalapril . Enalapril  induced inhibition of converting enzyme activity at all dose levels and with both dosing schedules . No adverse effect attributable to enalapril occurred during the study . The data indicate that once‐daily enalapril is safe and effective treatment for mild low‐renin essential hypertension Hypertension frequently complicates diabetes mellitus and is associated with an increased incidence of cardiovascular and microvascular complications . Angiotensin-I converting enzyme ( ACE ) inhibitors are effective antihypertensive agents and it has been suggested that they may improve glucose tolerance . We performed a double-blind , r and omized study comparing treatment for 8 weeks with cilazapril , a new ACE inhibitor , or placebo on metabolic variables in 22 hypertensive non-insulin-dependent diabetes mellitus ( NIDDM ) patients . At week 8 no significant changes in fasting plasma glucose , fasting plasma insulin , haemoglobin A1 and plasma lipids had occurred . The areas under the glucose [ placebo ( mean + /- SD ) : 10.7 + /- 3.27 and 10.6 + /- 2.53 ; cilazapril : 11.9 + /- 3.23 and 12.1 + /- 2.9 mmol/l per 180 min at 0 and 8 weeks , respectively ] and insulin curve  [ placebo ( median and range ) : 47.4 ( 31.4 - 165.1 ) and 65.3 ( 16.8 - 190.8 ) ; cilazapril : 51.1 ( 23.8 - 132.0 ) and 57.6 ( 29.0 - 150.1 ) mU/l per 180 min at 0 and 8 weeks , respectively ] after a st and ardized oral liquid test meal were unaltered . A significant decrease in mean arterial blood pressure was observed after cilazapril ( 122 + /- 8.6 and 106 + /- 8.3 mmHg at 0 and 8 weeks , respectively ) , in contrast to placebo ( 122 + /- 6.7 and 120 + /- 6.9 mmHg at 0 and 8 weeks , respectively ) . In conclusion , cilazapril does not affect metabolic control in hypertensive NIDDM patients , whereas it effectively reduces blood pressure The renal effects of long‐term antihypertensive treatment with enalapril were evaluated in 34 subjects ( age , 53 yr ; range , 27 to 65 ) with mild , uncomplicated hypertension . After receiving placebo for 4 wk , subjects were r and omly assigned to groups receiving incremental doses of enalapril ( 10 , 20 , or 40 mg/day for 4 wk each ) in a single morning dose or two divided doses , or of placebo . One subject who received enalapril  developed acute renal failure by the end of the study . There was no evidence of glomerular or tubular damage in the other subjects ; as measured by 24‐hr urinary protein excretion , urinary activity of N‐acetyl‐β‐D‐glucosaminidase , and uric acid clearance . During treatment with enalapril  , renal plasma flow ( measured with 131l‐iodohippurate sodium ) and glomerular filtration rate increased by 12.1 % and 6.8 % . Changes in renal plasma flow correlated inversely with age and final mean arterial pressure and correlated positively with initial plasma renin activity of subjects . Except for an occasional idiosyncratic adverse reaction , enalapril is a safe and effective antihypertensive drug with the unique ability to increase renal function despite a fall in renal perfusion pressure OBJECTIVE To test the antihypertensive and metabolic effects of lisinopril , 10 mg/d ( L ) ; hydrochlorothiazide , 12.5 and 25 mg/d ( H12.5 and H25 ) ; and its combination with lisinopril ( L/H12.5 and L/H25 ) against placebo in patients with mild to moderate ( stage I and stage II ) hypertension . DESIGN Multicenter , double-blind , placebo-controlled outpatient study of 12 weeks ' duration . PATIENTS After 4 weeks of single-blind placebo treatment , 505 patients whose sitting diastolic blood pressure was 100 to 114 mm Hg were r and omized into the study --467 patients completed it  ( placebo , 71 ; L , 80 ; H12.5 , 79 ; H25 , 77 ; L/H12.5 , 79 ; and L/H25 , 81 ) . The patients were seen in the clinic every 2 weeks , where measurements of their sitting and upright blood pressure and heart rate were taken 24 + /- 2 hours after drug administration . Complete blood cell counts with differential cell counts , blood chemistry studies , urinalyses , and electrocardiograms were done at baseline and during the study . Roentgenograms were done once at baseline . RESULTS Compared with placebo , all drug regimens decreased sitting and upright blood pressure ( P < .001 ) and had no effect on sitting and upright heart rate . The greatest effect was obtained with the combinations of L/H12.5 and L/H25 . There was no difference between L/H12.5 and L/H25 or between H12.5 and H25 . There were no serious clinical side effects except cough , which was slightly higher with L , L/H12.5 , and L/H25 . The only metabolic side effects were in serum potassium level , which was lower with H25 ( P < .01 ) , and serum glucose level , which was higher with H25 and L/H25 ( P < .01 ) . CONCLUSIONS The data suggest that ( 1 ) monotherapy of hypertension with L , H12.5 , H25 , L/H12.5 , and L/H25 was effective and well tolerated ; ( 2 ) the best results were achieved with L/H12.5 and L/H25 ; ( 3 ) lower doses of hydrochlorothiazide either alone or in combination with lisinopril were equipotent with higher doses and were free of metabolic side effects The objective of this study was to determine which of the common groups of antihypertensive drugs is most effective at lowering systolic blood pressure ( SBP ) in elderly patients with previously untreated hypertension and the percentage of patients controlled with single or sequential monotherapy . Subjects were recruited from patients attending other outpatient clinics and entered into the study if their SBP was more than 150 mm Hg after three visits . Patients were given a low and high dose of each of the main classes of drugs or placebo for 1 month each . The study was a balanced , r and omized crossover design with five periods : placebo ; angiotensin converting enzyme inhibitors ; beta-blocking drugs ; calcium-blocking drugs ; and thiazide diuretics .  Blood pressure ( BP ) was measured 24 to 26 h after the previous dose . A question naire for side effects was administered at each visit . Seventy-four patients entered the study . beta-Blockers could not be used in 15 patients because of asthma or bronchospasm and these had two placebo periods . There were 9 of 66 patients on P , 9 of 46 on beta-blockers , 4 of 65 on calcium-blocking drugs , 4 of 65 on diuretic , and 1 of 62 patients on ACE inhibitors who did not progress to the higher dose because of side effects . Decreases in SBP compared to r and omized placebo were calcium-blocking drugs 15 mm Hg = diuretic 13 mm Hg > ACE inhibitors 8 mm Hg = beta-blockers 5 mm Hg . Blood pressure decrease correlated with placebo BP ( P < .0005 , r = 0.53 to 0.70 ) . When corrected for placebo , target SBP ( < 140 mm Hg ) was reached in between 6 % to 15 % of patients on monotherapy . Sequential monotherapy achieved target in 29 % . Angiotensin converting enzyme inhibitors , calcium-blocking drugs , and diuretics had no more side effects than placebo . Patients on beta-blockers had more side effects and the well-being score was reduced . Diuretics and calcium-blocking drugs are more effective in elderly patients at lowering SBP pressure . beta-Blockers were relatively ineffective , were frequently contraindicated , and had more side effects . Monotherapy achieved control in only a small number of patients . In elderly people with essential hypertension , therapy should be instituted with diuretics or calcium-blocking drugs , but combination therapy will usually be required to achieve goal The antihypertensive effect of captopril , metoprolol , and hydrochlorothiazide was compared in 23 non-insulin-dependent ( NIDDM ) diabetic patients less than or equal to 75 years of age , with borderline to moderate primary hypertension . In a double blind , placebo-controlled cross-over trial the patients were treated with 25 to 50 mg captopril , 50 to 100 mg metoprolol , 12.5 to 25 mg hydrochlorothiazide , and placebo , each given twice daily for 8 weeks . Antidiabetic treatment remained unchanged during the study . After receiving placebo for a 4 week run-in period , arterial blood pressure was 168/101 + /- 93/10 ( mean + /- SEM ) mm Hg . Diastolic blood pressure was lowered significantly during all active treatment periods compared to the placebo value of 97 + /- 2 mm Hg : captopril , 92 + /- 1 mm Hg ; metoprolol , 90 + /- 1 mm Hg ; hydrochlorothiazide , 91 + /- 1 mm Hg . Metabolic variables were not significantly altered by captopril and metoprolol , while hydrochlorothiazide treatment increased hemoglobin A1c from 7.5 + /- 0.3 to 8.2 + /- 0.4 % ( P less than .001 ) , decreased high-density lipoprotein-cholesterol from 1.19 + /- 0.08 to 1.10 + /- 0.06 mmol/L ( P less than .05 ) . Glomerular filtration rate , urinary albumin excretion , orthostatic blood pressure response , and digital systolic blood pressure in the lower limb remained unchanged during the active treatment periods . The frequency of subjective adverse effects was acceptable during active treatment and not significantly different compared to placebo . We conclude that antihypertensive treatment for 8 weeks with captopril or metoprolol in NIDDM patients is well-tolerated and causes no deterioration in metabolic control and kidney function , while hydrochlorothiazide causes a slight deterioration in glycemic control and lipid profile The time to peak antihypertensive effect and the trough‐to‐peak ratio were determined in 64 Caucasian patients ( 19 men , 45 women ) with mild to moderate hypertension [ supine diastolic blood pressure ( DBP ) 95 to 115 mmHg ] . They received placebo or fosinopril 10 , 20 , or 40 mg once daily for 4 weeks . The study consisted of a 4‐week placebo lead‐in , 4 weeks ' double‐blind treatment , and a 1‐week placebo washout period . Vital signs were determined biweekly before dosing , and blood pressures were measured every 1 to 2 h during two 27‐h periods at the beginning and end of treatment . After the first and last doses of all three regimens , the peak effect on blood pressure occurred 5 to 7 h after all three dosages . Neither peak nor trough blood pressure changes showed a clear dose‐response relationship . Trough to peak ratios for the first dose , corrected for placebo effects , were 79 % for fosinopril 10 mg , 48 % for fosinopril 20 mg , and 74 % for fosinopril 40 mg , and the trough‐to‐peak ratios for the last dose were 41 % for fosinopril 10 mg , 32 % for fosinopril 20 mg , and 44 % for fosinopril 40 mg . In the 38 responders among the 48 patients receiving fosinopril  ( supine DBP decrease of at least 5 mmHg at 24 h postdose ) , trough‐to‐peak rations ranged from 50 to 81 % , and the range indicates that fosinopril is efficacious when administered once daily . Adverse effects were mild to moderate , and no patient discontinued treatment . Changes in the laboratory test results , electrocardiograms , or the results of physical examinations were unremarkable . Once‐daily fosinopril 10 , 20 , or 40 mg effectively and safely controlled blood pressure in patients with mild to moderate essential hypertension Cilazapril , an angiotensin converting enzyme ( ACE ) inhibitor with a long half-life , effectively reduced sitting diastolic blood pressure in patients with uncomplicated essential hypertension at dosages of 2.5 , 5.0 , and 10.0 mg/day , evaluated in a double-blind , placebo-controlled study . After a four-week placebo run-in period , 235 patients received either cilazapril or placebo for four weeks . At the end of the treatment period , significant decreases from baseline in sitting diastolic blood pressure were seen in all four groups ( mean decreases of 3.3 mm Hg with placebo and 6.4 , 9.2 and 8.3 mm Hg with 2.5 , 5.0 and 10.0 mg cilazapril , respectively ) . The cilazapril groups had significantly greater blood pressure reductions than did the placebo group ( p less than or equal to 0.02 ) . The 5.0 mg cilazapril dose was significantly more effective than the 2.5 mg dose ( p less than 0.03 ) . The response rate was notably greater in the cilazapril treatment groups than in the placebo group ( placebo , 27.5 % ; 2.5 mg cilazapril , 42.9 % ; 5.0 mg cilazapril 62.5 % ; 10.0 mg cilazapril , 50.0 % ) . Cilazapril was well tolerated at all three dosages The aim of this double-blind r and omized placebo-controlled study was to evaluate the antihypertensive and safety of fosinopril in mild essential hypertension . After a 2-week placebo period , patients received either placebo or fosinopril 20 mg , once daily . Thirty-four patients finished the study ( 18 patients in the placebo group and 16 patients in the fosinopril group ) .  Systolic blood pressure decreased from 160.1 + /- 22.1 mmHg to 156.0 + /- 24.2 in the placebo group ( NS ) and from 151.8 + /- 14.0 mmHg to 141.5 + /- 14.5 in the fosinopril group ( p < 0.005 ) ; diastolic blood pressure decreased from 100.1 + /- 2.4 mmHg to 94.3 + /- 7.4 mmHg in the placebo group ( p < 0.005 ) and from 100.8 + /- 4.8 mmHg to 88.1 + /- 9.0 mmHg in the fosinopril group ( p < 0.001 ) . Mean decrease in diastolic blood pressure was 5.7 mmHg in the placebo group and 12.6 mmHg in the fosinopril group ( p < 0.05 ) . A statistically significant difference was seen between the percentage of controlled patients in the two groups : 16.6 % in the placebo group vs 56.2 % in the fosinopril group ( p < 0.05 ) . No statistically significant difference in biochemical parameters was seen between the two groups . Tolerance was good and no patients were withdrawn from the study for adverse events In this multicenter , placebo-controlled , double-blind , 4 x 3 factorial design study , 1,162 patients r and omized into 12 parallel groups received either placebo  ( n = 97 ) , cilazapril ( CLZ 0.5 , 5 , or 10 mg ; n = 288 total ) , hydrochlorothiazide ( HCTZ 12.5 or 25 mg ; n = 198 total ) , or one of the six possible combinations of the two drugs ( n = 579 total ) given orally once daily for 4 weeks . The mean decrease from baseline in predose ( i.e. , 24 h postdose ) sitting diastolic blood pressure ( SDBP ) was statistically significantly ( p < 0.01 ) greater for all combinations studied compared to placebo , as well as to their respective monotherapy components . Synergistic antihypertensive effects were noted for the 5/12.5 mg CLZ/HCTZ combination therapy . The normalization ( SDBP < or = 90 mm Hg ) rate of the 5/12.5 mg CLZ/HCTZ combination was essentially additive with respect to the component monotherapies . The tolerability profile of the CLZ/HCTZ combination was similar to its respective components and comparable to placebo . The CLZ/HCTZ group reported low serum potassium ( K+ ) and high serum uric acid less frequently than the HCTZ group . Therefore , the CLZ/HCTZ combination ( 5 mg/12.5 mg ) is an option for hypertensive patients not responding to single drug CLZ therapy
target: The data do not suggest that any one ACE inhibitor is better or worse at lowering BP .
  ACE inhibitor doses above Max did not significantly lower BP more than Max .
  There are no clinical ly meaningful BP lowering differences between different ACE inhibitors .
background: BACKGROUND ACE inhibitors are widely prescribed for hypertension so it is essential to determine and compare their effects on blood pressure ( BP ) , heart rate and withdrawals due to adverse effects ( WDAE ) .
  OBJECTIVES To quantify the dose-related systolic and /or diastolic BP lowering efficacy of ACE inhibitors versus placebo in the treatment of primary hypertension .