title: Antihypertensive efficacy and safety of olmesartan medoxomil compared with amlodipine for mild-to-moderate hypertension Antihypertensive efficacy of lercanidipine at 2.5, 5 and 10 mg in mild to moderate essential hypertensives assessed by clinic and ambulatory blood pressure measurements Amlodipine versus chlorthalidone versus placebo in the treatment of stage I isolated systolic hypertension. Effect of Low-Dose Manidipine on Ambulatory Blood Pressure in Very Elderly Hypertensives Use of 24-h ambulatory blood pressure monitoring to assess blood pressure control: a comparison of olmesartan medoxomil and amlodipine besylate Effects of telmisartan and amlodipine in combination on ambulatory blood pressure in stages 1–2 hypertension Failure of psychological interventions to lower blood pressure: a randomized controlled trial The 24-Hour Efficacy of a New Once-Daily Formulation of Nifedipine A double-blind evaluation of the effect of amlodipine on ambulatory blood pressure in hypertensive patients. Sustained-release nicardipine in mild-to-moderate hypertension. Antihypertensive effects of a new sustained-release formulation of nifedipine. Evaluation of slow release nicardipine in essential hypertension by casual and ambulatory blood pressure measurements. Effects of acute versus chronic administration. The effect of amlodipine on ambulatory blood pressure in hypertensive patients. Reduced plasma cyclic GMP but normal renal responses to atrial natriuretic factor in pre-hypertension. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). The Antihypertensive Action of Isradipine in Mild Essential Hypertension Amlodipine lowers blood pressure without affecting cerebral blood flow as measured by single photon emission computed tomography in elderly hypertensive subjects. A comparison of the efficacies and duration of action of the angiotensin II receptor blockers telmisartan and amlodipine. Trough and peak effects of a single daily dose of nifedipine gastrointestinal therapeutic system (GITS) as assessed by ambulatory blood pressure monitoring. Italian Nifedipine GITS Study Group. Effectiveness of once-daily monotherapy with a new nifedipine sustained release calcium antagonist. 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 evaluation of the effect of amlodipine on ambulatory blood pressure. Arterial and Antihypertensive Effects of Nitrendipine: A Double-Blind Comparison Versus Placebo
abstract: The antihypertensive efficacy of the angiotensin II receptor blocker olmesartan medoxomil has been shown to compare favourably with that of other antihypertensive agents . This r and omized , double-blind study compared the antihypertensive efficacy of the starting dose of olmesartan medoxomil with that of the calcium channel blocker amlodipine besylate ( amlodipine ) in subjects with mild-to-moderate hypertension . Following a 4-week , single-blind , placebo run-in period , 440 subjects aged ⩾18 years were r and omized to the starting dose of olmesartan medoxomil ( 20 mg/day ) , amlodipine ( 5 mg/day ) , or placebo for 8 weeks . Subjects were evaluated by  24-h ambulatory blood pressure monitoring ( ABPM ) and by seated cuff blood pressure ( BP ) measurements at trough . The primary end point was the change from baseline in mean 24-h diastolic blood pressure ( DBP ) by ABPM at Week 8 . Secondary end points included change from baseline in mean 24-h ambulatory systolic blood pressure ( SBP ) at 8 weeks , change from baseline in mean seated trough cuff DBP and SBP measurements , and response and control rates for DBP < 90 and < 85 mmHg . Control rates for SBP < 140 and < 130 mmHg were also calculated . Olmesartan medoxomil and amlodipine produced significantly greater reductions in ambulatory and seated DBP and SBP compared with placebo . Mean reductions in ambulatory and seated BP were similar between the two active agents ; however , in the olmesartan medoxomil group , significantly more patients achieved the SBP goal of < 130 mmHg and the DBP goal of < 85 mmHg . Both drugs were well tolerated at the recommended starting dose . Although amlodipine was associated with a higher incidence of oedema , this did not reach statistical significance . Olmesartan medoxomil is an effective antihypertensive agent , with BP-lowering efficacy at the starting dose similar to that of amlodipine , and is associated with more patients achieving the rigorous BP goals of SBP < 130 mmHg and DBP < 85 mmHg Objective To evaluate the antihypertensive effect of lercanidipine once a day at three different doses ( 2.5 , 5 and 10 mg ) by clinic and ambulatory blood pressure . Methods After 3 weeks of a placebo run-in , 243 mild to moderate essential hypertensives ( mean ± SD age 51 ± 8 years ) were r and omly allocated to lercanidipine at 2.5 , 5 or 10 mg or a placebo for 4 weeks , in a double-blind parallel-group design . At the end of each period , supine clinic blood pressure ( st and ard sphygmomanometry ) and 24 h ambulatory blood pressure ( Spacelabs 90207 ) were measured . The duration and homogeneity of the antihypertensive effect of the active drug compared with placebo over 24 h was evaluated by calculating the smoothness index , the ratio of the mean of the 24 hourly blood pressure changes to the corresponding SD . The higher the smoothness index , the greater and the smoother is the antihypertensive effect of a drug over the 24 h. Results In 211 patients with valid clinic blood pressure data at the end of treatment  , larger systolic/diastolic blood pressure reductions were found in the 5 mg ( 10 ± 12/8 ± 6 mmHg ; P < 0.05 versus placebo , diastolic blood pressure only ) and the 10 mg ( 12 ± 1/9 ; ± 7 mmHg ; P < 0.05 versus placebo , both pressures ) lercanidipine groups than in the placebo ( 5 ± 11/4 ± 8 mmHg ) and 2.5 mg lercanidipine ( 7 ± 12/6 ± 7 mmHg ) groups . In 105 patients with complete 24 h  ambulatory blood pressure recordings , there were significantly ( P < 0.05 versus placebo ) larger reductions in the 10 mg ( 9 ± 7/7 ± 5 mmHg ) than the 2.5 mg ( 1 ± 10/1 ± 6 mmHg ) and placebo ( 2 ± 6/1 ± 4 mmHg ) groups . The reduction in 24 h blood pressure with 5 mg lercanidipine ( 6 ± 7/4 ± 5 mmHg ) was significantly greater compared with placebo for diastolic pressure only , and when hourly average blood pressure changes were considered , this reduction did not extend to the final hours of the dosing interval . No significant changes in the clinic or 24 h heart rate were induced by placebo or lercanidipine . The smoothness index was significantly ( P < 0.05 ) lower for 2.5 mg lercanidipine and placebo ( 0.2 ± 0.5 and 0.3 ± 0.7 for systolic and 0.1 ± 0.4 and 0.2 ± 0.7 for diastolic blood pressure ) than for the 5 and 10 mg doses ( 0.7 ± 1 and 1 ± 0.7 for systolic and 0.7 ± 1 and 1 ± 0.9 for diastolic blood pressure ) . Conclusions At a dose of 10 mg , lercanidipine had a significant and durable antihypertensive effect over 24 h , but at 5 mg , the effect was less consistent and did not last 24 h. There was no clinical ly relevant reduction in clinic or ambulatory blood pressure with 2.5 mg lercanidipine , and the effect was superimposable on that of placebo The study was to compare the effects of amlodipine ( calcium channel antagonist ) , chlorthalidone ( diuretic ) , and placebo in adults more than 50 years of age with stage 1 isolated systolic hypertension ( ISH ) . After a 4-week placebo run-in phase , 150 patients were r and omly assigned in a double-blind fashion to treatment with 5 mg of amlodipine ( n = 48 ) , 15 mg of chlorthalidone ( n = 50 ) , or placebo ( n = 52 ) . Patients who failed to meet the systolic blood pressure ( BP ) reduction goal by week 4 had their dose increased to 10 mg of amlodipine or 30 mg of chlorthalidone , and maintained at this increased dose for 12 weeks . Results showed a mean reduction ( mean + /- SD ) in sitting systolic BP from baseline to the last treatment visit of -14.6+/-12.2 mm Hg ( 95 % confidence interval [ CI ] -18.2 , -11.0 ) , -14.0+/-13.46 mm Hg ( 95 % CI -17.8 , -10.2 ) , and -3.4+/-11.83 mm Hg ( 95 % CI -6.7 , -0.1 ) for the amlodipine , chlorthalidone , and the placebo treatment groups , respectively . Both active treatments showed significantly greater reductions than the placebo group ( P < or = .001 ) , but were not significantly different from each other . Sixty-seven percent of the amlodipine , 69 % of the chlorthalidone , and 25 % of the placebo-treated patients reached the protocol defined systolic BP goal ( P = .001 ) . Both active treatment groups showed a trend of better systolic BP response in older patients ( > or = 65 years ) . Secondary efficacy measures including pulse pressure , st and ing systolic , diastolic , and the 24-h ambulatory BP were also statistically significantly improved for both active treatments at the end of treatment , except for chlorthalidone in st and ing diastolic BP . Adverse events that occurred during the study were as expected and were well tolerated . The results of this study support the efficacy and safety of amlodipine and chlorthalidone for the treatment of stage 1 ISH during 20 weeks of treatment Summary . To evaluate the effect of manidipine 10 mg on 24-hour ambulatory blood pressure ( BP ) and heart rate ( HR ) in very elderly hypertensive patients , 54 patients aged 76–89 years ( mean age 81.8 years ) with systolic blood pressure ( SBP ) > 160 mmHg and diastolic blood pressure ( DBP ) > 90 mmHg were studied . After a 4-week placebo washout period , patients were r and omized to receive manidipine 10 mg or placebo , both administered once daily for 8 weeks . Patients were checked after the initial run-in placebo phase and every 4 weeks thereafter . At each visit casual BP and HR were measured . At the end of the placebo period and after 8 weeks of active treatment , noninvasive 24-hour ambulate blood pressure measurement ABPM was performed . Manidipine significantly lowered casual sitting and st and ing SBP ( P < 0.001 ) and DBP ( P < 0.001 ) at the trough level . ABPM showed a significant decrease in 24-hour SBP and DBP values ( P < 0,001 ) , daytime SBP and DBP ( P < 0.001 ) , and night-time SBP ( P < 0.001 ) and DBP ( P < 0.005 ) . In addition , ABPM confirmed a consistent antihypertensive activity throughout the 24-hour dosing interval , without effect on the circadian BP profile . The trough/peak ratio was 0.67 for SBP and 0.59 DBP . No statistically significant change in HR was observed . The treatment was well tolerated , and there were no serious side effects . In conclusion , in very elderly hypertensive patients , once-daily administration of manidipine 10 mg was well tolerated and effective in reducing casual as well ambulatory BP Objective Olmesartan medoxomil is an angiotensin II receptor blocker with similar antihypertensive efficacy as the calcium channel blocker amlodipine besylate in patients with mild-to-moderate hypertension . In addition to a drug 's ability to lower blood pressure , the effectiveness of the agent in enabling patients to achieve specific blood pressure targets is an important clinical consideration . This secondary analysis of a r and omized , double-blind study compared the efficacy of olmesartan medoxomil with that of amlodipine besylate in achieving ambulatory blood pressure goals among patients with mild-to-moderate hypertension . Methods Following a 4-week placebo run-in , 440 study participants aged ≥18 years were r and omized to olmesartan medoxomil ( 20 mg/day ) , amlodipine besylate ( 5 mg/day ) , or placebo for 8 weeks . The proportion of participants achieving specific systolic and diastolic ambulatory blood pressure goal levels was calculated by dividing the number of participants who had achieved a particular blood pressure goal by the total number of patients in the intent-to-treat population . Results After 8 weeks of treatment , a mean 24-h ambulatory blood pressure of < 130/80 or < 130/85 mmHg was achieved by significantly more participants in the olmesartan medoxomil group ( 18.1 and 30.4 % , respectively ) than in the amlodipine besylate ( 7.0 and 14.0 % , respectively ) or placebo ( 1.9 % for both ) groups . The target daytime ambulatory blood pressure of < 135/85 mmHg was achieved by more participants in the olmesartan medoxomil group than in the amlodipine besylate group ( 15.8 vs. 5.8 % , respectively ; P<0.01 ) . Conclusion In a previous publication of the same study , we demonstrated that starting doses of olmesartan medoxomil and amlodipine besylate produced similar mean reductions in blood pressure . In this sub analysis of the blood pressure data from that primary publication , however , olmesartan medoxomil therapy was shown to result in a greater proportion of patients achieving specific ambulatory blood pressure goals than therapy with amlodipine besylate . As blood pressure goal attainment may be of more direct clinical relevance than numerical blood pressure lowering , the achievement of blood pressure goals should be a key efficacy parameter assessed in clinical trials of antihypertensive medications Background Evaluation of combination therapy with antihypertensive agents by clinic blood pressure ( BP ) measurements may yield results that differ from out-of-office BP readings . This is of clinical relevance because out-of-office BP values are of prognostic importance . We studied the effects of combining telmisartan and amlodipine on ambulatory BP in patients with stages 1–2 hypertension . Methods We conducted an 8-week , placebo-controlled , double-blind , 4 × 4 factorial design trial in which 562 patients with clinic diastolic BP at least 95 and 119 mmHg or less were r and omized to receive telmisartan ( 0 , 20 , 40 , or 80 mg ) and /or amlodipine ( 0 , 2.5 , 5 , or 10 mg ) .  Ambulatory BP monitoring  was performed at baseline and after 8 weeks of treatment ; the end points of interest were the changes from baseline in 24-h systolic and diastolic BP . Secondary end points included the proportion of responders ( ≥10 mmHg BP reduction from baseline and /or < 130/80 mean 24-h BP ) and controlled patients ( < 130/80 mmHg mean 24-h BP ) . Results Combination therapies of telmisartan and amlodipine  lowered 24-h BP to a larger extent than the corresponding monotherapies at all doses . Mean reductions from baseline in 24-h BP for the combination of the highest doses of telmisartan ( 80 mg ) and amlodipine ( 10 mg ) were −22.4/−14.6 versus −11.9/−6.9 mmHg for amlodipine ( 10 mg ) and −11.0/−6.9 mmHg for telmisartan ( 80 mg ) ( P<0.0001 for each comparison ) . In addition , BP response and control rates ( 24-h BP < 130/80 mmHg ) were significantly higher with the combination therapy versus the monotherapy groups . Conclusion These findings show that telmisartan and amlodipine in combination provide substantial 24-h BP efficacy that is superior to either monotherapy in patients with stages 1 and 2 hypertension Background Previous studies have suggested that psychological interventions may be effective in reducing blood pressure . Using rigorous methodology and 24-hour monitoring of ambulatory blood pressure , we compared 2 psychological interventions with treatment using a first-line antihypertensive drug in terms of their efficacy in lowering blood pressure in patients with mild primary hypertension . Methods In this prospect i ve , open-label r and omized controlled trial ( RCT ) , 65 adult patients with mild , uncomplicated hypertension were r and omly assigned to receive one of the following interventions for 12 weeks : ( 1 ) pharmacotherapy with hydrochlorothiazide 12.5 titrated to 25 mg/d ; ( 2 ) individualized behavioural psychotherapy , consisting of ten 1-hour sessions of stress reduction training with a psychologist ; or ( 3 ) self-help psychotherapy , consisting of a 1.5-hour session with a psychologist and then daily sessions that involved reading a self-help manual and listening to an audiotape . The primary outcome measure was mean change in ambulatory blood pressure from baseline to week 12 . Resting blood pressure readings were taken in the clinic , and adverse events were recorded . Results Monitoring of ambulatory blood pressure over 24 hours showed that hydrochlorothiazide therapy significantly reduced both systolic and diastolic blood pressure relative to baseline , and that this reduction was significantly greater than that achieved with either individualized behavioural psychotherapy or self-help psychotherapy ( mean reduction [ st and ard error ; SE ] −11.03 [ 2.53 ] / −6.06 [ 1.56 ] mm Hg v. −0.08 [ 2.38 ] / 0.29 [ 1.47 ] mm Hg v. −1.23 [ 2.83 ] / −0.71 [ 1.75 ] mm Hg , respectively ; p = 0.01 ) . Neither form of psychological therapy significantly lowered 24-hour ambulatory blood pressure relative to baseline . Conclusion For patients with primary elevated blood pressure , 2 psychological interventions did not lower 24-hour ambulatory blood pressure , whereas hydrochlorothiazide  reduced blood pressure , as expected . The findings of this RCT represent an important addition to the evidence for health care practitioners and for patients seeking psychological interventions to reduce blood pressure Summary Nifedipine GITS ( Gastro-Intestinal Therapeutic System ) is a recently launched long-acting formulation of nifedipine . The aim of the Italian  Nifedipine GITS Study was to determine the duration of the antihypertensive effect of once-daily nifedipine GITS in out patients with essential hypertension . After a 2-week placebo run-in period , 126 patients with mild to moderate essential hypertension ( diastolic BP 95 to 114 mm Hg ) were r and omised to receive nifedipine GITS 30 mg ( n = 42 ) , nifedipine GITS 60 mg ( n = 42 ) or placebo ( n = 42 ) , once daily in a double-blind fashion for 4 weeks . At the end of the run-in and treatment periods ,  ambulatory BP monitoring  was performed ( Spacelabs 90202 or 90207 device ) to provide regular 15-minute BP readings for 24 to 36 hours . In the 81 patients with at least 24 hours of valid ambulatory BP data , the average systolic and diastolic BP changes after treatment with nifedipine GITS 30 mg ( n = 25 ) , nifedipine GITS 60 mg ( n = 28 ) and placebo ( n = 28 ) were −16.5/−10.8 , −16.3/−10.0 and + 0.4/+0.9 mm Hg , respectively . BP changes with nifedipine GITS differed significantly ( p < 0.01 ) from those with  placebo . Heart rate was not significantly altered by nifedipine GITS . The effects of nifedipine GITS and placebo on ambulatory BP 24 hours and 36 hours after the last dose were evaluated in 56 patients with complete 36-hour ambulatory BP profiles . After 24 hours , both doses of nifedipine GITS caused significant ( p < 0.01 ) reductions in systolic and diastolic BP . After 36 hours , the reduction in ambulatory BP induced by nifedipine GITS was less pronounced than after 24 hours ; the changes in systolic BP produced by both nifedipine GITS doses were still significant ( p < 0.01 ) , whereas the change in diastolic BP was significant only after the 60 mg dose ( p < 0.05).Trough : peak ratios of the antihypertensive effect of nifedipine GITS were calculated by comparing the highest average hourly BP reduction between 2 and 6 hours postdose ( peak reduction ) and the BP change at 24 hours postdose ( trough reduction ) in the 81 patients with valid 24-hour ambulatory BP data . Trough : peak ratios were 90.5 % ( systolic BP ) and 76.3 % ( diastolic BP ) for nifedipine GITS 30 mg , and 109.3 % ( systolic BP ) and 98.6 % ( diastolic BP ) for nifedipine GITS 60 mg . The ratios were further increased if placebo-induced BP changes were taken into account . In conclusion , the antihypertensive effect of nifedipine GITS is maintained for more than 24 hours postdose , and is uniform over this period , without any undue imbalance between the peak BP effect and that observed immediately before the subsequent dose Amlodipine is a new long-acting calcium antagonist that has a long half-life and appears to be suitable for once-daily administration . A double-blind , r and omized , parallel , placebo-controlled study was conducted to evaluate the effect of amlodipine on ambulatory blood pressures in hypertensive patients . The study consisted of a 4-week single-blind placebo run-in phase , followed by 4 weeks of double-blind therapy . Ambulatory blood pressure was measured for 24 h at the end of the placebo run-in phase and after double-blind therapy . Sixteen patients were r and omized to receive either amlodipine 5 mg or placebo in a 2:1 ratio . Amlodipine 5 mg daily significantly reduced supine and st and ing blood pressure 24 h postdose . Ambulatory blood pressure recordings revealed adequate blood pressure control throughout the 24-h dosing interval . Amlodipine was well tolerated and only two patients reported side effects -- neither was withdrawn from therapy . No treatment-related abnormalities were noted . It was concluded that amlodipine 5 mg daily was effective antihypertensive therapy throughout the 24-h dosing period in the patients studied , and it was well tolerated STUDY OBJECTIVE To evaluate the antihypertensive effects and tolerability of a sustained release preparation of nicardipine ( NIC SR ) , a dihydropyridine calcium channel antagonist . DESIGN AND INTERVENTIONS After at least 1 week without receiving antihypertensive medications and 2 weeks of single-blind placebo treatment , the patients were r and omized to receive in a double-blind fashion , either placebo or NIC SR 30 , 45 , or 60 mg twice daily at 12-h intervals for 12 weeks . Supine and st and ing blood pressure were measured in all patients and 24-h ambulatory blood pressure monitoring was performed in a subset of 75 patients at baseline during treatment with single-blind placebo and during the double-blind treatment period . SETTING Academic and private hypertension research clinics . PATIENTS Two hundred sixty-four patients with supine diastolic blood pressures of 95 to 114 mm Hg , ranging in age from 22 to 75 years and in weight from 50 to 137 kg , approximately evenly divided by gender ; one third were black . RESULTS In comparison with placebo , all doses of NIC SR significantly reduced systolic and diastolic blood pressures , with a trend toward greater effects from 45 to 60 mg twice daily than with 30 mg twice daily . At all doses , reduction of blood pressure from baseline levels was fully apparent within the first 2 weeks of therapy and was maintained throughout the remaining 10 weeks of the trial . Ambulatory blood pressure monitoring demonstrated that the antihypertensive effect was maintained throughout the dosing interval . Adverse effects were primarily extensions of pharmacologic activity ( eg , pedal edema , flushing ) . Six percent of the placebo group and 10 percent of the combined NIC SR groups experienced at least one adverse event that was judged to be probably related to therapy . Withdrawals due to unacceptably high blood pressure totaled 5 percent of the combined NIC SR groups and 25 percent of the placebo group . CONCLUSIONS Sustained-release nicardipine at a dose of 30 to 60 mg every 12 h provided effective and generally well-tolerated antihypertensive control throughout the day in most patients with mild-to-moderate essential hypertension The blood pressure response to a new sustained-release formulation of nifedipine was evaluated in an 8-week , double-blind , placebo-controlled study . Twenty-nine patients with mild essential hypertension were r and omized to receive placebo ( N = 9 ) , 30 mg nifedipine ( N = 10 ) , or 60 mg nifedipine ( N = 10 ) . During treatment , 30-mg and 60-mg doses of nifedipine administered once daily decreased office blood pressures from 137/98 + /- 8/2 mm Hg and 141/98 + /- 15/2 mm Hg at baseline , respectively , to 126/89 + /- 9/7 mm Hg and 126/86 + /- 6/7 mm Hg ( P less than .005 ) . Noninvasive automatic ambulatory blood pressure monitoring demonstrated a marginally significant ( P less than .10 ) reduction in the mean 24-hour blood pressure of 2/6 + /- 8/8 mm Hg and 5/6 + /- 9/9 mm Hg for patients taking 30 mg and 60 mg nifedipine once daily , respectively . Diastolic blood pressure load ( the percentage of ambulatory diastolic blood pressure readings greater than 90 mm Hg ) during 24 hours was decreased by 41 % and 35 % , with 30 mg and 60 mg nifedipine administered once daily , respectively . No significant dose response to nifedipine at these dose levels was observed . Although the once-daily formulation of nifedipine achieved effective control of office blood pressure , similar control was not observed in awake and 24-hour periods in all patients We conducted a r and omized placebo-controlled double-blind study in 40 hypertensive subjects to assess the antihypertensive effect of a new galenic form of nicardipine administered at a dosage of 50 mg twice daily for 3 weeks . Regardless of whether blood pressure was measured by st and ard mercury sphygmomanometer , non-ambulatory automatic oscillometry or a Remler ambulatory blood pressure recorder , it dropped by a significantly larger amount in the nicardipine group than in the placebo group . In the control group , a placebo effect was observed with the ambulatory diastolic blood pressure recording , whereas it was not observed with hospital blood pressure measurements , especially when using the serial measurements performed for 30 min by an automatic recorder . The fall in blood pressure measured with the Remler recorder was correlated with the fall measured 10 - 20 min during one acute intravenous nicardipine perfusion before the trial , although the correlation coefficients do not suggest clinical ly relevant predictability of nicardipine efficacy at the individual level . The present findings support the need for controlled double-blind trials with careful office blood pressure measurements Certain high-risk population s , such as diabetics and blacks , have sustained elevation in blood pressure and heart rate throughout the day and night , with blunting of the usual diurnal variability pattern . This may contribute to their higher incidence of left ventricular hypertrophy ( blacks ) and cardiovascular complications ( diabetics ) . Hypertensives who maintain a diurnal pattern of blood pressure variation still exhibit higher daytime and nocturnal blood pressure levels than normotensives . Thus , to achieve maximum effectiveness in treating hypertension , 24-hour control of blood pressure is necessary . Antihypertensive agents should effectively reduce blood pressure consistently throughout a 24-hour period . The objective of this study was to assess the effects of amlodipine , 5 mg once daily , on blood pressure measured by 24-hour ambulatory monitoring in a r and omized , double-blind , placebo-controlled single-site study . Patients with mild-to-moderate essential hypertension were r and omized to receive amlodipine ( n = 11 ) or placebo ( n = 5 ) in a 2:1 ratio . A 4-week single-blind placebo run-in period was followed by a 4-week double-blind phase . Ambulatory monitoring of blood pressure was carried out for 24 hours at the end of each 4-week phase . Patients receiving amlodipine had significantly lower blood pressure compared with placebo 24 hours after the last dose ( supine blood pressure -25.1/-10.1 mm Hg ; st and ing blood pressure -21.2/-9.7 mm Hg ) after 4 weeks of treatment . This effect was clearly demonstrated by the 24-hour postdose measurement and the mean blood pressure over the 24-hour interval as measured by ambulatory recordings . ( ABSTRACT TRUNCATED AT 250 WORDS The amount of , and response of the kidneys to , endogenous natriuretic factor(s ) could be important in the pathogenesis of essential hypertension . Search ing for possible disturbance(s ) related to atrial natriuretic factor ( ANF ) and its second messenger , cyclic guanosine monophosphate ( c-GMP ) , we assessed plasma immunoreactive ( ir ) ANF and c-GMP , effective renal plasma flow ( ERPF ) , glomerular filtration rate ( GFR ) , urinary c-GMP , absolute and fractional ( FE ) excretions of sodium ( Na ) and chloride ( Cl ) before and during infusions of low ANF doses or vehicle ( V ) in 7 normotensive sons of essential hypertensive parents ( SEH ) compared with 7 sons of normotensive parents ( SN ) . Each subject was infused at 2-week intervals in a single-blind r and omized sequence with 4 different solutions : V only or ANF 0.004 , 0.008 and 0.016 microgram/kg/min , infused over 90 min . Plasma irANF was lower in SEH than in SN ( p < 0.001 ) during vehicle infusion . Basal plasma c-GMP levels were , on all 4 different study days lower ( p < 0.05 to < 0.01 ) in SEH in SN . Response of plasma c-GMP to infused ANF was also slightly decreased in SEH ( p < 0.05 to < 0.01 ) . BP , ERPF and GFR did not differ between SEH and SN and were unchanged during the 4 infusions . Urinary c-GMP excretion , FENa and FECl increased dose-dependently during ANF ( p < 0.05 to < 0.0001 ) but not V infusions . These findings indicate that at the stage of pre-hypertension a disturbance in the ANF-c-GMP regulatory pathway may occur , which is expressed primarily at the circulatory rather than the renal excretory level CONTEXT Antihypertensive therapy is well established to reduce hypertension-related morbidity and mortality , but the optimal first-step therapy is unknown . OBJECTIVE To determine whether treatment with a calcium channel blocker or an angiotensin-converting enzyme inhibitor lowers the incidence of coronary heart disease ( CHD ) or other cardiovascular disease ( CVD ) events vs treatment with a diuretic . DESIGN The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial ( ALLHAT ) , a r and omized , double-blind , active-controlled clinical trial conducted from February 1994 through March 2002 . SETTING AND PARTICIPANTS A total of 33 357 participants aged 55 years or older with hypertension and at least 1 other CHD risk factor from 623 North American centers . INTERVENTIONS Participants were r and omly assigned to receive chlorthalidone , 12.5 to 25 mg/d ( n = 15 255 ) ; amlodipine , 2.5 to 10 mg/d ( n = 9048 ) ; or lisinopril , 10 to 40 mg/d ( n = 9054 ) for planned follow-up of approximately 4 to 8 years . MAIN OUTCOME MEASURES The primary outcome was combined fatal CHD or nonfatal myocardial infa rct ion , analyzed by intent-to-treat . Secondary outcomes were all-cause mortality , stroke , combined CHD ( primary outcome , coronary revascularization , or angina with hospitalization ) , and combined CVD ( combined CHD , stroke , treated angina without hospitalization , heart failure [ HF ] , and peripheral arterial disease ) . RESULTS Mean follow-up was 4.9 years . The primary outcome occurred in 2956 participants , with no difference between treatments . Compared with chlorthalidone ( 6-year rate , 11.5 % ) , the relative risks ( RRs ) were 0.98 ( 95 % CI , 0.90 - 1.07 ) for amlodipine ( 6-year rate , 11.3 % ) and 0.99 ( 95 % CI , 0.91 - 1.08 ) for lisinopril ( 6-year rate , 11.4 % ) . Likewise , all-cause mortality did not differ between groups . Five-year systolic blood pressures were significantly higher in the amlodipine ( 0.8 mm Hg , P = .03 ) and lisinopril ( 2 mm Hg , P<.001 ) groups compared with chlorthalidone , and 5-year diastolic blood pressure was significantly lower with amlodipine ( 0.8 mm Hg , P<.001 ) . For amlodipine vs chlorthalidone , secondary outcomes were similar except for a higher 6-year rate of HF with amlodipine ( 10.2 % vs 7.7 % ; RR , 1.38 ; 95 % CI , 1.25 - 1.52 ) . For lisinopril vs chlorthalidone , lisinopril had higher 6-year rates of combined CVD ( 33.3 % vs 30.9 % ; RR , 1.10 ; 95 % CI , 1.05 - 1.16 ) ; stroke ( 6.3 % vs 5.6 % ; RR , 1.15 ; 95 % CI , 1.02 - 1.30 ) ; and HF ( 8.7 % vs 7.7 % ; RR , 1.19 ; 95 % CI , 1.07 - 1.31 ) . CONCLUSION Thiazide-type diuretics are superior in preventing 1 or more major forms of CVD and are less expensive . They should be preferred for first-step antihypertensive therapy The antihypertensive effect of isradipine compared with placebo was assessed in 28 male patients ( aged 40–64 years ) with mild-to-moderate essential hypertension . After withdrawal of all previous antihypertensive treatment , these patients were entered into a 4-week placebo period followed by r and omization to receive double-blind , for 8 weeks , either placebo ( n = 14 ) or isradipine at 1.25–2.5 mg twice daily ( n = 14 ) . Twenty-four-hour ambulatory blood pressure was measured by Accutracker at the end of the placebo period and at the end of active treatment . In the isradipine  group . both systolic and diastolic blood pressures decreased significantly ( p < 0.0001 ) whereas blood pressure increased in those taking placebo . In addition , isradipine as monotherapy con-trolled blood pressure throughout the day and night , and especially during the early morning , in these patients AIM To evaluate the effect of amlodipine on blood pressure and cerebral blood flow in elderly subjects with mild to moderate hypertension . METHODS A double-blind , parallel group study of 26 patients . After a 4-week placebo run-in period , amlodipine ( 5 - 10 mg ) or matching placebo was given once daily for 8 weeks . RESULTS Amlodipine significantly reduced blood pressure compared with baseline . Diastolic blood pressure was significantly reduced by amlodipine compared with placebo ( P < 0.02 to P < 0.01 ) . Ambulatory blood pressure monitoring showed that blood pressure control was sustained over the 24-h dosing interval . Relative regional cerebral blood flow , assessed using single photon emission computed tomography , was not significantly affected by amlodipine . Three placebo patients , but no amlodipine patients , withdrew because of adverse events . CONCLUSION Amlodipine was a well-tolerated and effective antihypertensive agent , and did not reduce regional cerebral blood flow in elderly hypertensive patients OBJECTIVES : To compare the antihypertensive effects and duration of action of the angiotensin II receptor antagonist , telmisartan , amlodipine , and placebo in patients with mild-to-moderate hypertension using both conventional clinic blood pressures and ambulatory blood pressure monitoring ( ABPM ) . METHODS : After a 4-week single-blind , placebo run-in period , qualifying patients were r and omly allocated in double-blind manner to be administered 40 mg telmisartan ( n = 73 ; increased to 80 and 120 mg as necessary for patients whose diastolic blood pressure ( DBP ) remained > 90 mmHg ) ; 5 mg amlodipine ( n = 78 ; titrated to 5 mg and titrated to 10 mg for patients whose DBP remained > 90 mmHg ) ; or placebo ( n = 81 ) . ABPM was performed at the end of the baseline period and again at the end of 12 weeks of double-blind treatment . RESULTS : Telmisartan and amlodipine treatments significantly decreased trough supine systolic blood pressure and DBP ( P < 0.001 , measured conventionally ) to a similar extent ( by 13.1/7.1 and 14.0/7.1 mmHg , respectively , at the end of 12 weeks ' treatment ) compared with placebo . Both drugs also significantly reduced 24 h mean systolic blood pressures and DBP compared with placebo ( P < 0.0001 ) , measured using ABPM , maintaining control of blood pressure throughout the dosing period . Reductions in DBP with telmisartan were greater ( P < 0.05 ) than those with amlodipine during the night-time interval and the last 4 h of the dosing period . Twenty-four-hour mean ABPM DBP < 85 mmHg were observed in 71 % of telmisartan patients and in 55 % of patients administered amlodipine . In addition , heart rates in patients treated with telmisartan were lower than heart rates in those treated with amlodipine during the final 4 h of the dosing period ( P = 0.0003 ) and during the morning interval ( P = 0.005 ) . Generally , both telmisartan and amlodipine were well tolerated , however , drug-related edema occurred significantly more commonly ( P < 0.05 ) among the patients administered amlodipine than it did among patients administered either telmisartan or placebo . CONCLUSIONS : Clinic blood pressure measurements detected no difference between the antihypertensive effects and duration s of action of telmisartan and amlodipine , both agents producing statistically significant reductions compared with placebo . ABPM measurements , however , revealed differences between the efficacies at specific time points within the dosing periods . These findings highlight the potential importance of the use of ABPM for evaluating and comparing efficacies of antihypertensive agents AIM To evaluate the antihypertensive efficacy of nifedipine gastrointestinal therapeutic system ( GITS ) , a slow-release formulation of nifedipine . PATIENTS AND METHODS A r and omly allocated , double-blind , placebo-controlled trial was set up with 126 essential hypertensives who were assessed by ambulatory blood pressure monitoring . A 2-week placebo run-in phase was followed by treatment with nifedipine GITS at 30 mg ( n = 42 ) or 60 mg ( n = 42 ) or with a placebo ( n = 42 ) once a day for 4 weeks . At the end of each period , 24- to 36-h ambulatory blood pressure was measured at 15-min intervals by a SpaceLabs 90202 or 90207 device . The peak effect of nifedipine was assessed as the lowest average hourly value of systolic/diastolic blood pressure 2 - 6 h after drug intake subtracted from the baseline value for the same hour , and the trough effect as the mean systolic/diastolic blood pressure obtained 24 h after the dose subtracted from the baseline value for the same hour . RESULTS In the 81 patients with 24-h valid ambulatory blood pressure data  , 24-h , daytime and night-time mean systolic and diastolic blood pressures were significantly decreased by nifedipine GITS at both doses , but were not changed by the placebo . The trough : peak ratios for systolic and diastolic blood pressure were 90.5 and 76.3 % for 30 mg nifedipine GITS and 109.3 and 98.6 % for 60 mg nifedipine GITS . Correction by trough and peak effects in the placebo group further increased the trough : peak ratios . In 51 patients with 36-h ambulatory blood pressure data , trough : peak ratios above the United States Food and Drug Administration recommended value of 50 % were found 30 h after the dose , and systolic blood pressure was still significantly lower 36 h after the nifedipine GITS dose Data from 2 separate multicenter , double-blind clinical studies following the same protocol , except for the selection of doses , were pooled to evaluate the efficacy and tolerability of fixed doses of a new sustained-release ( SR ) formulation of nifedipine compared with placebo in 388 patients with mild to moderate uncomplicated essential hypertension . After a 3 - 6 week placebo washout period , the patients were r and omized to receive either placebo or nifedipine SR-20 mg ( study I only ) , 50 mg , 100 mg , or 150 mg ( study II only ) . Among the 278 patients who completed 6 weeks of active therapy , mean supine diastolic blood pressure reductions from pretreatment baseline were 5.9 , 9.3 , 9.2 , 11.1 , and 13.2 mm Hg in the placebo , 20- , 50- , 100- , and 150-mg groups , respectively . The reductions achieved in each of the nifedipine SR groups were statistically significant versus baseline values ( p less than 0.001 ) . All nifedipine-SR doses reduced supine systolic blood pressure significantly more than placebo ( p less than 0.001 ) . In addition , there was a significant linear relationship between the log of the dose and the blood pressure reduction ( p less than 0.05 ) . Automated ambulatory blood pressure recordings performed in 221 of the patients showed that the blood pressure was lowered evenly through the entire 24-hour dosing period . The doses that were effective and associated with the fewest adverse reactions were 20 mg and 50 mg once daily 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 effects of amlodipine on ambulatory blood pressure were investigated in patients with mild-to-moderate hypertension . Ambulatory recordings showed that amlodipine maintained diastolic and systolic blood pressure below baseline levels for a full 24-h period without altering the normal circadian rhythm . No reflex tachycardia occurred and side effects were rare Summary : Arterial effects evaluated by carotid-femoral , brachial-radial , and femoral-tibial pulse wave velocity and antihypertensive effect evaluated by 24-h ambulatory blood pressure ( BP ) monitoring were measured in 17 hypertensive patients before and 24 h after once-daily nitrendipine ( 20 mg ) administration . After a 15-day placebo period , a double-blind study of nitrendipine versus placebo was performed for 1 month . After nitrendipine dosing , BP measured by sphygmomanometer 24 h after the last drug intake showed a significant decrease as compared with the pretreatment period . Ambulatory BP mean values were also significantly decreased for systolic and diastolic BP ( SBP , DBP ) . This decrease predominated during the day but was observed nocturnally only after 6 a.m. Twenty-four hours after the last tablet intake of nitrendipine , carotid-femoral and brachial-radial pulse wave velocities were significantly reduced , whereas femoral-tibial wave velocity was unchanged , indicating that markers of arterial rigidity might be substantially modified and that the modifications were partly unrelated to BP changes . The results provide evidence that in hypertensive subjects nitrendipine 20 mg given once daily for 1 month produces an arterial effect for 24 h , in association with BP reduction
target: Once-daily dihydropyridine calcium channel blockers appeared to lower blood pressure by a relatively constant amount throughout the 24-hour dosing interval .
  Six dihydropyridine calcium channel blockers studied in this review lowered blood pressure by a relatively similar amount each hour over the course of 24 hours .
background: BACKGROUND Calcium channel blockers are a heterogeneous class of drugs , including dihydropyridine and non-dihydropyridine subgroups , commonly used in the treatment of hypertension .
  A systematic review of the 24-hour time course of the blood pressure-lowering effect has not been published .
  OBJECTIVES To assess how much variation there is in hourly systolic and diastolic blood pressure lowering by dihydropyridine calcium channel blockers over a 24-hour period in people with hypertension aged 18 years or over , with baseline systolic blood pressure of at least 140 mmHg or diastolic blood pressure of at least 90 mmHg , or both .