title: Patient Acceptance of Guanethidine as Therapy for Mild to Moderate Hypertension: A Comparison with Reserpine Treatment of hypertension in the elderly: I. Blood pressure and clinical changes. Results of a Department of Veterans Affairs Cooperative Study. Reserpine plus hydrochlorothiazide and sotalol plus hydrochlorothiazide in Black and Indian hypertensive patients. The Systolic Hypertension in the Elderly Program (SHEP): an intervention trial on isolated systolic hypertension. SHEP Cooperative Research Group. Chlorthalidone plus reserpine versus hydrochlorothiazide plus reserpine in a stepped-care approach to the treatment of essential hypertension. [Combined uni- and multicenter double-blind studies in hypertensive patients. Comparison of blood pressure measurements]. Step 2 regimens in hypertension. An assessment. Diltiazem for treatment of essential hypertension: a double-blind controlled study with reserpine. Different concepts in first-line treatment of essential hypertension. Comparison of a low-dose reserpine-thiazide combination with nitrendipine monotherapy. German Reserpine in Hypertension Study Group. Propranolol in the treatment of essential hypertension. Anti-hypertensive adrenergic-blocking agents: effects on sodium balance, the renin-angiotensin system and haemodynamics. A randomised crossover comparison of reserpine and sustained-release nifedipine in hypertension. [The effect of an antihypertensive drug during psychological stress. A double-blind study]. Combination of a thiazide, a vasodilator and reserpine compared with methyldopa plus hydrochlorothiazide in the treatment of hypertension in Zimbabwe. Low-dose reserpine/thiazide combination in first-line treatment of hypertension: efficacy and safety compared to an ACE inhibitor. 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). Diuretic-based treatment and cardiovascular events in patients with mild renal dysfunction enrolled in the systolic hypertension in the elderly program. Mild hypertension: a clinical trial conducted in hospital general practice. Effects of treatment in hypertension. Results of a controlled study. Effect of atenolol and reserpine on selected events in the systolic hypertension in the elderly program (SHEP). Evaluation of drug treatment in mild hypertension: VA-NHLBI feasibility trial. Plan and preliminary results of a two-year feasibility trial for a multicenter intervention study to evaluate the benefits versus the disadvantages of treating mild hypertension. Prepared for the Veterans Administration-N Comparative evaluation of Rauwolfia whole root and reserpine Antihypertensive properties of cryptenamine used with reserpine and methyclothiazide.
abstract: The relative benefits and risks of reserpine and guanethidine were compared in patients with thiazide-treated mild to moderate hypertension ( diastolic pressure 95–115 mm Hg ) . Fortynine ambulant patients ( 30 men , 19 women ) were treated throughout the study with hydrochlorothiazide , 50 mg/day . In this double blind crossover study each drug was added in grade d increments until a predetermined therapeutic response was obtained , blood pressure measurements and side effect scores were evaluated biweekly . Major conclusions of the study were : 1 ) guanethidine , as well as reserpine , will reduce mild to moderate blood pressures to normal ; 2 ) in most cases , side effects which did occur while taking guanethidine or reserpine were well tolerated and neither drug was clearly superior . Side effects associated with larger doses of guanethidine employed in severe hypertension were absent or only slightly bothersome . Thus , guanethidine appears to have a good benefit-to-risk ratio in the therapy of mild to moderate hypertension and offers a number of advantages over drugs commonly used in this syndrome . This study refutes the common belief that guanethidine must be reserved only for the treatment of more severe degrees of hypertension We compared the efficacy and adverse effects of antihypertensive drug regimens in 690 men past age 60 with diastolic blood pressure 90 - 114 mm Hg and systolic blood pressure less than 240 mm Hg . They received either a low ( 25 - 50 mg ) or high ( 50 - 100 mg ) dose of hydrochlorothiazide daily . Of 644 patients who completed the hydrochlorothiazide titration , 375 ( 58.2 % ) were responders ( diastolic blood pressure less than 90 and less than or equal to 5 mm Hg below baseline ) and 92.8 % of these completed a 6-month maintenance period . Blood pressure was reduced from 157.6/98.5 mm Hg by 18.3/9.5 mm Hg with low dose hydrochlorothiazide and by 20.4/9.6 mm Hg with high dose hydrochlorothiazide ; more patients achieved goal blood pressure with the high dose . Whites and blacks responded equally . Serum potassium less than 3.5 mmol/l occurred in 104 of 321 ( 32.3 % ) of the high dose versus 62 of 333 ( 18.6 % ) of the low dose hydrochlorothiazide patients . The 269 nonresponders to hydrochlorothiazide were r and omly assigned in a double-blind study to receive hydralazine , methyldopa , metoprolol , or reserpine in addition to hydrochlorothiazide ; 79.2 % responded to the addition of the second drug and 87.3 % of these completed a 6-month maintenance phase . Overall , there were no significant efficacy differences among the step 2 regimens . We conclude that the lower dose of hydrochlorothiazide was nearly as effective as the higher dose , and the addition of a second drug was effective and generally well tolerated in elderly patients Fifty patients ( 25 Blacks and 25 Indians ) suffering from mild-to-moderate hypertension ( supine diastolic blood pressure 100 - 105 mmHg ) were studied in order to compare the antihypertensive effect of a combination of a beta-blocker ( sotalol hydrochloride 160 mg/d ) plus a thiazide derivative ( hydrochlorothiazide 25 mg/d ) ( Sotazide ; B-M ) with that of a combination of reserpine 0,1 mg/d ( Serpasil ; Ciba ) plus hydrochlorothiazide 25 mg/d ( Dichlotride ; Frosst MSD ) . The combination of reserpine plus hydrochlorothiazide was found to be as effective as that of sotalol plus hydrochlorothiazide in lowering the blood pressure in both the Black and the Indian patients . Two patients taking the combination containing reserpine developed side-effects , but this did not occur in any of those taking the combination containing sotalol . We feel that in developing countries , where the cost of therapy is important , reserpine in a dosage of less than 0,1 mg/d plus a thiazide derivative in low dosage is preferable to a beta-blocker plus a thiazide derivative in the treatment of hypertension The Systolic Hypertension in the Elderly Program ( SHEP ) is a r and omized double-blind placebo-controlled trial to determine if antihypertensive treatment of isolated systolic hypertension ( ISH ) [ systolic blood pressure ( SBP ) greater than or equal to 160 mmHg , diastolic blood pressure ( DBP ) less than 90 mmHg ] reduces the 5 year incidence of fatal and nonfatal stroke . Between March 1 , 1985 and January 15 , 1988 , 4736 persons ( target 4800 ) with ISH , age 60 years and over , were enrolled . Potential participants met blood pressure ( BP ) and age criteria . Those on antihypertensive medication prior to enrollment without documented diastolic hypertension had their medication tapered and discontinued , and then met BP criteria ( 33 % of cohort ) . Stepped-care therapy with chlorthalidone and atenolol ( alternative , reserpine ) or matching placebos was initiated as first and second steps . At baseline the trial population was 43.1 % male , 56.9 % female ; 13.9 % black , 86.1 % non-black . Also , the mean age was 71.6 years ; the mean SBP was 170.3 mmHg and the mean DBP was 76.6 mmHg ; 59.8 % had codeable resting electrocardiographic abnormalities .  The trial is now in follow-up phase with scheduled termination in 1991 The efficacy of thiazide-like chlorthalidone , 50 mg , plus reserpine , 0.25 mg , was compared with that of hydrochlorothiazide , 50 mg , plus reserpine , 0.125 mg , in a six-week double-blind study of 57 patients with essential hypertension unresponsive to diet control and diuretic ( step 1 ) therapy . An average decrease in diastolic pressure of 17.0 mm Hg was attained at the end of week 6 by the chlorthalidone/reserpine group ; the average drop in the hydrochlorothiazide/reserpine group was 18.6 mm Hg . Both treatment groups displayed greater blood pressure control each week than the preceding week ; and , at the end of week 6 , both groups attained control of at least 5 mm Hg below the diastolic goal pressure of 90 mm Hg . The chlorthalidone/reserpine-treated group required fewer titrations than the hydrochlorothiazide/reserpine-treated group . There were no reports of frequent or severe side effects with either drug In a double-blind study to investigate the antihypertensive effect of a fixed triple combination with 0.05 mg reserpine , 2.5 mg clopamide and 0.4 mg dihydroergocristine in comparison to a fixed double combination with 0.05 mg reserpine and 2.5 mg clopamide , a patient subgroup of 34 patients followed a unicenter ( central unit , ' institute ' ) as well as a multicenter ( established physicians ) study design . The patients visited both investigation units on the day of admission to the study ( week 0 ) , after four weeks and after eight weeks of therapy ( after the morning intake of the drugs ) . The paper in h and looks at the results of this subgroup with respect to the conformity of blood pressure values in the two investigative units . The analyses confirm the already published results of the entire study : Both combinations proved to be highly effective antihypertensive drugs . The triple combination showed therapeutical advantages for systolic blood pressure after four weeks , for diastolic pressure after eight weeks of therapy at the ' institute ' as well as , although less distinct , in the medical offices . A comparison of the individual values did not show a convincing coherence of the measurements between institute and offices . All investigated possible systematic sources of error ( different methods of measurement , days or times of measurement ) could be excluded by correlation statistics as a reason for the divergences . The results show the necessity -- particularly in multicenter studies --of a careful documentation of all accompanying data ( e.g. method or time of measurement ) as well as a greatest possible st and ardization of investigation ( e.g. identical measuring apparatus and investigator . A single-blind clinical trial compared step 2 combination therapy consisting of 50 or 100 mg of hydroflumethiazide plus either 0.125 to 0.250 mg of reserpine , 500 to 2,000 mg of methyldopa , or 80 to 320 mg of propranolol hydrochloride , in 59 patients whose elevated blood pressure ( BP ) failed to respond adequately to the thiazide alone . After nine weeks of treatment , diastolic BP was reduced below 90 mm Hg in all 20 patients treated with the  reserpine-hydroflumethiazide combination , in 13 of the 19 patients treated with methyldopa and hydroflumethiazide , and in 16 of the 20 patients treated with propranolol and hydroflumethiazide .  Changes in laboratory values were not substantial ; adverse reactions occurred only in the methyldopa group . Although the three treatment regimens were similar with respect to safety and efficacy , the reserpine-hydroflumethiazide combination offers the advantages of more convenient dosage at lower cost In a double-blind , parallel , 12-week trial , antihypertensive effects of diltiazem and reserpine were compared in 107 patients with essential hypertension .  Diltiazem reduced blood pressure from 176/100 mmHg to 154/86 mmHg after 12 weeks , and reserpine reduced blood pressure from 171/96 mmHg to 155/85 mmHg . The difference between diltiazem and reserpine was not statistically significant . However , among a subset of patients given 180 mg/day of diltiazem , a significantly better antihypertensive effect was achieved than among a subset given 0.3 mg of reserpine . The incidence of side effects and complications in the diltiazem group was about one half that in the reserpine group ( 12.3 % and 27.1 % , respectively ) . Side effects of diltiazem were mild , and the drug was extremely well tolerated . These results show that diltiazem is an effective antihypertensive drug for the treatment of mild to moderate essential hypertension Low-dose combination therapy has been proposed as a rational first-line approach to hypertension treatment . We compared the efficacy and tolerability of the fixed combination of reserpine ( 0.1 mg ) plus the thiazide clopamid ( 5 mg ) with its single components and the calcium-antagonist nitrendipine ( 20 mg ) in a r and omized , double-blind , parallel study of 273 hypertensive patients with diastolic blood pressure ( BP ) between 100 and 114 mm Hg . The four groups did not differ regarding baseline characteristics ( mean age , 58 years ; 51 % men ; mean BP after a 2-week placebo period , 158 to 160/103 to 104 mm Hg ) . After 6 weeks of treatment with one capsule daily , mean reductions in sitting BP from baseline at 24 hours after dosing in the reserpine-clopamid combination , reserpine , clopamid , and nitrendipine groups were -23.0/-17.1 , -14.0/-11.7 , -13.6/-11.9 , and -11.6/-12.3 mm Hg , respectively ( 2P < .01 ) . The corresponding normalization rates ( diastolic BP < 90 mm Hg ) were 55 % , 40 % , 36 % , and 33 % ( 2P = .11 ) . All patients whose BP had not been normalized at this point received two capsules of the respective medication once daily from weeks 7 to 12 . At week 12 , mean BP reductions were -25.7/-18.1 , -14.6/-12.2 , -17.7/-13.4 , and -14.9/-15.3 mm Hg in the four groups , respectively ( 2P < .01 ) . The respective normalization rates were 69 % , 35 % , 39 % , and 45 % ( 2P < .0001 ) . Linear regression modeling indicated that reserpine and clopamid combined acted more than additively . As regards tolerability , adverse experiences were observed in 27 % , 28 % , 29 % , and 48 % of patients , respectively ( 2P < .05 ) . The respective rates of premature discontinuation because of adverse effects were 3 % , 3 % , 7 % , and 13 % ( 2P = .06 ) . In conclusion , a low-dose combination of reserpine and clopamid lowered BP significantly more than both the components alone and nitrendipine . Moreover , the combination was tolerated as well as its components and significantly better than nitrendipine . Thus , the use of this low-dose reserpine-thiazide combination appears to be a rational alternative to conventional monotherapy in the first-line treatment of hypertension In a series of 450 patients with mild essential hypertension , propranolol alone ( P ) , propranolol plus hydrochlorothiazide ( P+T ) , propranolol plus hydralazine ( P+H ) , and propranolol plus hydrochlorothiazide plus hydralazine ( P+T+H ) were compared to reserpine plus hydrochlorothiazide ( R+T ) . Comparison was based on reduction of diastolic blood pressures ( BP ) to below 90 mm Hg and at least 5 mm Hg less than initial BP after six months of treatment . This was achieved in 92 % of patients who received P+T+H , 88 % taking R+T , 81 % receiving P+T , 72 % on P+H and 52 % taking P alone . The number of drop-outs , morbid events , and terminating side effects were insignificantly different among the various regimens . In this study , P and P+H were less effective , while P+T and P+T+H were as effective as the st and ard regimen 1 . The changes in plasma volume , haemodynamic variables , plasma renin activity and plasma aldosterone were studied in forty-one hypertensive patients after administration of adrenergic-blocking agents .  Four drugs were used : alpha-methyldopa ( fourteen patients ) , guanethidine ( ten patients ) , clonidine ( nine patients ) and reserpine ( eight patients ) . Drugs were administered orally during 7 days ' hospitalization on a normal sodium diet ( 110 mmol/day ) . 2 . The four drugs had similar effects : a significant decrease in blood pressure , a significant increase in plasma volume and no change in stroke volume . 3 . With alpha-methyldopa and guanethidine , heart rate , plasma renin activity and plasma aldosterone were unchanged . 4 . With reserpine and clonidine , heart rate and plasma renin activity were significantly decreased , whereas plasma aldosterone did not change significantly . 5 . This study suggests that the decrease in plasma renin activity was related to the lowering of the heart rate rather than to sodium retention and that adrenergic-blocking agents can impair the normal relationship between stroke index and plasma volume , between plasma volume and plasma renin activity , and between plasma renin activity and plasma aldosterone OBJECTIVE To compare the effectiveness of the combination of hydrochlorothiazide ( HCT ) plus sustained-release nifedipine with the combination of HCT plus reserpine in lowering  high blood pressure ( BP )  unresponsive to HCT monotherapy . DESIGN An open , r and omised crossover drug trial . SETTING Out patients ' clinic in Parirenyatwa Hospital , Harare , a tertiary referral centre . SUBJECTS 32 Black patients of both sexes with newly diagnosed or previously treated hypertension aged between 21 and 65 years who had a BP > 140/95 after receiving HCT 25 mg daily for four weeks were studied . INTERVENTION Patients were kept on HCT 25 mg daily and were r and omised to receive either reserpine 0.25 mg daily or nifedipine ( Adalat Retard ) 20 mg bd for four weeks . This was followed by a two week washout period during which patients received HCT 25 mg daily only . After the washout period patients were crossed over to the alternative treatment for four weeks . Patients were kept on HCT 25 mg daily throughout the trial . MAIN OUTCOME MEASURES The main outcome measure was the fall in BP which was taken as the difference between the BP at baseline and the BP at the end of each treatment period . Both systolic blood pressure ( SBP ) and diastolic blood pressure ( DBP ) measurements were taken . RESULTS Both second line drugs were effective in lowering SBP and DBP and there was no significant difference between them . Nifedipine reduced SBP by 18.9 mmHg ( 95 % CI 12.1 to 25.7 ) and DBP by 9.6 mmHg ( 95 % CI 7.2 to 12.0 ) . Reserpine reduced SBP by 15.9 mmHg ( 95 % CI 8.4 to 23.4 ) and DBP by 11.1 mmHg ( 95 % CI 7.5 to 14.6 ) . However , only two patients attained the target DBP of < or = 90 mmHg after each active treatment period . CONCLUSION AND RECOMMENDATIONS Since both agents were equally effective in reducing both SBP and DBP and reserpine is much cheaper than nifedipine , it is recommended that for a developing country like Zimbabwe , the combination of HCT and reserpine at the above doses should be used as the first step to treat mild to moderate hypertension without evidence of end organ damage . However , further trials should compare BP lowering effects as well as end organ protection offered by the trial drugs A sample of 20 patients suffering hypertension ( with a moderate rise in blood pressure ) was r and omly divided into two treatment groups of equal size . The patients of one group received antihypertension treatment with the combination drug Briserin ¿ ( containing 0.1 mg reserpine , 5 mg clopamide , 0.5 mg dihydroergocristin/per tablet ) ; the other patients who served as  control group  , received a matched placebo . After a fortnight 's treatment , the responsiveness of both groups to five different psychologically stressing situations ( those with cognitive and /or emotional overload ) was tested . Analysis of covariance revealed clinical ly significant differences in the mean systolic and diastolic pressure scores of the two groups . The scores of the treatment group were lower not only under stress but also at rest . There was in interaction between rise of blood pressure under stress and kind of stress in the two groups , i.e. , in situations with heavy emotional and /or cognitive load the differences in the pressure scores of the two groups were less substantial than in situations with a low or medium load . The treatment had no systematic effect on heart rate in this sample . In the treatment group reaction time , perceptual speed , and short-term memory were impaired as compared with the control group ; but these differences did not reach a level of significance Brinerdin ( S and oz ) , a combination of a diuretic ( clopamide 5 mg ) , a vasodilator ( dihydro-ergocristine 0.5 mg ) and reserpine ( 0.1 mg ) ( CDR ) was compared with methyldopa ( MD ) plus hydrochlorothiazide ( HCT ) for antihypertensive effect , adverse reactions , compliance and patient preference in an open cross-over trial . Eighteen patients completed both arms of the trial and 5 patients who completed the CDR arm were withdrawn while on the MD arm because of adverse effects in 4 and poor control in 1 . On HCT 50 mg daily the mean baseline systolic blood pressure was 163.9 + /- 16.3 mmHg and the diastolic blood pressure was 105.9 + /- 6.7 mmHg . On CDR these were reduced to systolic blood pressure 140.3 + /- 15.1 mmHg and diastolic blood pressure 87.8 + /- 9.3 mmHg . On MD + HCT the systolic blood pressure was reduced to 138.5 + /- 16.9 mmHg and the diastolic blood pressure to 88.9 + /- 10.3 mmHg . The differences between the two treatment periods in systolic blood pressure ( 1.8 mmHg ; 95 % confidence interval ( CI ) - 4.1 + 7.7 mmHg ) and diastolic blood pressure ( 1.1 mmHg ; 95 % CI - 4.6 + 2.4 mmHg ) were not significant with P values of 0.6 and 0.7 respectively . Compliance was 98.2 % for CDR and 94.7 % for MD + HCT ( P = 0.02 ) . Unusual sleepiness occurred more frequently in the MD arm ( P less than 0.01 ) . Thirteen patients chose to continue on CDR , 2 on MD + HCT and 3 had no preference ( P = 0.005 ) . CDR is similar in antihypertensive effect to MD + HCT but is better tolerated with fewer withdrawals , fewer adverse effects , better compliance and has more patients electing to continue taking it The concept of initiating treatment of mild-to-moderate hypertension with a low-dose combination of reserpine and the thiazide clopamide in comparison to monotherapy with an ACE inhibitor was investigated . A total of 127 adult out patients with diastolic blood pressure between 100 and 114 mmHg were r and omized into this double-blind , parallel group study . After a 2-week wash-out period and a subsequent 2-week placebo run-in period , they were allocated to once-daily treatment with 0.1 mg reserpine plus 5 mg clopamide ( R/C ) , or 5 mg enalapril . If diastolic blood pressure was not normalized after 3 weeks of therapy ( i.e. DBP < 90 mmHg ) , the dosage was doubled from week 4 to 6 . The primary efficacy variables were the change from baseline in mean sitting diastolic and systolic blood pressure ( DBP/SBP ) after 3 weeks of therapy . Secondary variables included the change in DBP and SBP after 6 weeks of therapy , the BP normalization rates at 3 and 6 weeks and , concerning tolerability , the rates of adverse events after 6 weeks of therapy . An intent-to-treat analysis was performed . The reserpine/ clopamide and enalapril groups did not differ with regard to demographic and baseline characteristics ( mean age 57 or 58 years , respectively ; 63 % or 56 % males , respectively ; mean SBP/DBP after the 2-week placebo period = 156 mmHg/104 mmHg in both groups ) . After 3 weeks of treatment with one capsule daily , mean SBP/DBP reduction from baseline ( 24 h after last medication intake ) in the R/C combination group was -19.6/ -17.0 mmHg , in the enalapril group -6.1/ -9.5 mmHg ( between-group comparison : 2p < 0.01 for both parameters ) . The normalization rates for DBP ( < 90 mmHg ) were 64.1 % ( R/C ) and 28.6 % ( enalapril ) ( 2p < 0.01 ) . Adverse events that were considered possibly or definitely drug-related by the investigator were noted in 11 patients ( 17.2 % ) in the R/C group and in 9 patients ( 14.3 % ) in the enalapril group ( NS ) . Two patients in the enalapril group discontinued the study prematurely due to adverse events ( cough ; skin eruption ) . In the treatment of mild-to-moderate hypertension , a low-dose combination of reserpine and clopamide once a day is considerably more effective than , and as tolerable as , 5 - 10 mg of enalapril once a day . These findings suggest that treatment with a combination of different antihypertensives with different modes of action in low doses is a rational alternative to conventional monotherapy in the first-line treatment of hypertension . Besides , the " old " reserpine-diuretic regimen also in these days appears to be a rational alternative to " modern " monotherapies 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 BACKGROUND It is expected that the treatment of hypertension in patients with renal disease decreases the risk of cardiovascular events , but the evidence in these patients is lacking . OBJECTIVE To assess the effect of diuretic-based treatment on cardiovascular events in patients with isolated systolic hypertension and renal dysfunction . METHODS A total of 4336 persons aged 60 years and older with systolic blood pressures of 160 mm Hg and higher and diastolic blood pressures of less than 90 mm Hg were r and omly assigned to receive either placebo or chlorthalidone ( 12.5 - 25.0 mg/d ) , with the addition of atenolol ( 25 - 50 mg/d ) or reserpine ( 0.05 - 0.10 mg/d ) if needed , and observed for 5 years . The risk of first-occurring cardiovascular events , including stroke , transient ischemic attack , myocardial infa rct ion , heart failure , coronary artery bypass surgery , angioplasty , aneurysm , endarterectomy , sudden death , or rapid death , was stratified according to baseline serum creatinine levels ( 35.4 - 84.0 , 84.1 - 101.6 , 101.7 - 119.3 , and 119.4 - 212.2 micromol/L [ 0.4 - 0.9 , 1.0 - 1.1 , 1.2 - 1.3 , and 1.4 - 2.4 mg/dL ] ) . RESULTS Systolic blood pressure reduction was not affected by baseline serum creatinine levels . Active treatment did not affect the risk of serum creatinine levels becoming elevated during follow-up . The risk of hypokalemia with active treatment decreased significantly with increasing baseline serum creatinine levels . In the 4 baseline serum creatinine groups , the relative risk ( 95 % confidence interval ) of cardiovascular events developing with active treatment was 0.73 ( 0.54 - 0.97 ) , 0.63 ( 0.49 - 0.82 ) , 0.62 ( 0.44 - 0.87 ) , and 0.59 ( 0.38 - 0.91 ) . The results were similar for the outcomes of stroke or coronary artery events and in analyses stratified by sex or age . CONCLUSION Diuretic-based treatment of patients with isolated systolic hypertension prevents the development of cardiovascular events in older persons with mild renal dysfunction To compare findings in a hospital trial of hypotensive drugs with those in a general practice trial several patients with mild hypertension were studied at the same time in hospital and in general practice . They received bendrofluazide and potassium chloride or bendrofluazide , potassium chloride , and reserpine according to a double-blind crossover protocol , and blood biochemical values were studied over eight weeks and six months . When reserpine was withdrawn from nine women they followed a modified protocol comparing bendrofluazide and potassium chloride with potassium chloride alone . The blood pressure values measured by the general practitioners were similar to those measured in hospital . Both the diuretic alone and the diuretic with reserpine produced significant falls in blood pressures . Although plasma renin activity increased on diuretic treatment , continued treatment did not produce a further increase , and levels gradually declined towards normal Abstract Morbidity , mortality , and target organ function have been followed in a double-blind study of a predominantly Negro clinic population with mild to moderately severe hypertension over a 2-year period . Patients were placed r and omly on either hypotensive drug therapy ( reserpine , thiazide , guanethedine ) or matched placebos . There were 6 treatment failures among 45 patients in the treatment group and 19 failures among 42 patients in the placebo group . All but one of the failures in the placebo group improved or cleared upon early institution of appropriate hypertensive and supportive therapy . Abnormalities in carbohydrate metabolism and serum uric acid levels were found in patients receiving long-term thiazide therapy .  Hypertensive disease in the Negro population of Baltimore is a serious , life-threatening condition . Our study provides evidence of the need for continuous close supervision , and the provision of organized teams devoted to the care , of such a population The effect of atenolol and reserpine on incidence of strokes , coronary heart disease ( CHD ) , cardiovascular disease ( CVD ) , and mortality  was assessed in 4736 persons aged 60 years and older with isolated systolic hypertension . Participants were r and omized to either chlorthalidone ( 2371 ) , with step-up to atenolol , or reserpine if needed , or placebo ( 2365 ) . The average baseline SBP/DBP was 170/77 mm Hg . In the active treatment group , step 1 , dose 1 was chlorthalidone , 12.5 mg/day ; dose 2 was 25 mg/day . For step 2 , dose 1 was atenolol 25 mg/day ( or reserpine 0.05 mg/day if atenolol was contraindicated ) ; dose 2 was 50 mg/day ( reserpine , 0.10 mg/day ) . During 4.5 years average follow-up , 32 % ( 757 ) of the active treatment group were on atenolol , with an average exposure of two years and 8 % ( 193 ) were on reserpine with an average exposure of 1.7 years . Overall there were 96 strokes , 140 CHD events and 289 CVD events among the 2365 active group participants . Using time-dependent lifetable regression with adjustment for several variables , the addition of either atenolol or reserpine to chlorthalidone did not substantially alter the risk ratios for chlorthalidone alone . The relative risk for CHD events for atenolol versus no atenolol was 1.04 ( 95 % confidence interval : 0.58 , 1.86 ) and for reserpine versus no reserpine was 0.93 ( 95 % confidence interval : 0.29 , 2.96 ) . The relative risk for atenolol  were 0.84 ( 95 % confidence interval : 0.54 , 1.30 ) for death , 1.34 ( 95 % confidence interval : 0.80 , 2.28 ) for stroke , and 1.07 ( 95 % confidence interval : 0.71 , 1.61 ) for CVD . For reserpine , the corresponding relative risks and confidence intervals were 0.65 ( 0.26 , 1.59 ) for death , 0.27 ( 0.04 , 2.26 ) for stroke , and 0.55 ( 0.20 , 1.49 ) for CVD . Thus , the beneficial effects in several outcomes in Systolic Hypertension in the Elderly Program ( SHEP ) were due to the treatment regimen of lowering blood pressure based on low-dose chlorthalidone ( plus atenolol or reserpine as required to meet blood pressure criteria ) . Additional ( independent ) benefits attributable to atenolol or to reserpine were not identified . However , a greater number of patients might have been necessary to adequately evaluate potential differential effects of these drugs , especially for reserpine A feasibility trial to investigate the practicality of determining the advantages and disadvantages of prompt pharmacologic treatment for mild hypertension was jointly funded by the Veterans Administration and the National Heart , Lung and Blood Institute . Its clinical phase has been completed , and it demonstrated 1 . that the required relatively young asymptomatic population could be enrolled in the study and 2 . that it could be persuaded to adhere to the protocol for 2 years ; however , it was evident that intensive efforts would be required in both areas . The feasibility trial screened almost 120,000 potential subjects over a period of 16 months to r and omize about 1,000 subjects at four clinical centers . These men and women were 21 to 50 years old , had diastolic pressures from 85 to 105 mm Hg as out patients , and had no evidence of cardiovascular renal abnormalities . They were r and omized in double-blind fashion into active drug therapy and placebo groups . Stepped care therapy involved 50 mg chlorthalidone ( Step 1 ) , 100 mg chlorthalidone ( Step 2 ) and 100 chlorthalidone plus 0.25 mg reserpine ( Step 3 ) . Death , myocardial infa rct ion , stroke , angina pectoris , and congestive heart failure were the " major " morbid events that were looked for ; also recorded were " minor " morbid events consisting primarily of electrocardiographic arrhythmias . The development of significant hypertension was considered a treatment failure . Side effects were carefully tabulated in both active drug and placebo groups . The study revealed an average drop in diastolic pressure of almost 12 mm Hg for active drug group and less than half of that for the placebo group ; once established 6 months after r and omization , the new pressure levels persisted almost without change throughout the study . Although the feasibility trial was not design ed to answer the primary question regarding the benefits of treatment , the events were tabulated for each group . A total of 12 placebo-treated subjects developed significant hypertension and were put on active drug . There was not a significant difference between the two groups in the incidence of " major " morbid events ; a total of eight active and five placebo patients developed myocardial infa rct ion or died suddenly . There , however , was an excess of arrhythmias among the active drug subjects ( 17 in the active group versus 8 in the placebo group on the basis of preliminary data ) . Finally , there were twice as many side effects and 20 times as many chemical abnormalities among the active as among the placebo subjects . A protocol for a full scale study of the benefits of pharmacologic therapy in mild hypertensives has been prepared and is ready for implementation as needed ; it involves relatively minor modifications of the protocol tested in the feasibility trial To compare the antihypertensive effect of a Rauwolfia whole root‐chlorothiazide combination with reserpine plus chlorothiazide , subjects were selected who had average diastolic pressures of 90 mm . Hg or more at home , in the sitting position . In a double‐blind study providing 3 months on each regimen with a 6 week placebo period intervening , no significant difference in antihypertensive effect was demonstrated between the whole root Rauwolfia‐chlorothiazide combination and the reserpine plus chlorothiazide Abstract By a double‐blind crossover method , the hypotensive effects and side effects of cryptenamine were studied in 22 patients with Group 1 or 2 essential hypertension . The dosage administered was 2.5 mg . of methyclothiazide alone and a combination of 2.5 mg . of methyclothiazide and : ( a ) 2.0 mg . of cryptenamine , ( b ) 0.1 mg . of reserpine , and ( c ) 1.0 mg . of cryptenamine and 0.1 mg . of reserpine . Each preparation was administered four times each day for 8 weeks . The mean decrease in diastolic blood pressure with methyclothiazide alone was 10.5 mm . Hg ; with methyclothiazide and cryptenamine , 15 mm . Hg ; with methyclothiazide and reserpine , 21.6 mm . Hg ; and with methyclothiazide , reserpine , and cryptenanmine , 23.5 mm . Hg . Two patients receiving methyclothiazide and cryptenamine were unable to complete the study because of nausea or depression . Mild side effects were more frequent with the combinations . Hypokalemia was noted in 50 % of the patients , and small increases in levels of uric acid , urea , and blood sugar were without complication
target: A dose of reserpine 0.5 mg/day or greater achieved the SBP effects .
  AUTHORS ' CONCLUSIONS Reserpine is effective in reducing SBP roughly to the same degree as other first-line antihypertensive drugs .
background: BACKGROUND Many antihypertensive agents exist today for the treatment of primary hypertension ( systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg , or both ) .
  R and omised controlled trials ( RCTs ) have been carried out to investigate the evidence for these agents .
  There is , for example , strong RCT evidence that thiazides reduce mortality and morbidity .
  Some of those trials used reserpine as a second-line therapy .
  However , the dose-related blood pressure reduction with this agent is not known .
  OBJECTIVES The primary objective of this review was to quantify the dose-related efficacy of reserpine versus placebo or no treatment in reducing systolic blood pressure ( SBP ) or diastolic blood pressure ( DBP ) , or both .
  We also aim ed to evaluate the dose-related effects of reserpine  on mean arterial blood pressure ( MAP ) and heart rate ( HR ) , as well as the dose-related effects on withdrawals due to adverse events .