Combination of a thiazide, a vasodilator and reserpine compared with methyldopa plus hydrochlorothiazide in the treatment of hypertension in Zimbabwe. A randomised crossover comparison of reserpine and sustained-release nifedipine in hypertension. Low-dose reserpine/thiazide combination in first-line treatment of hypertension: efficacy and safety compared to an ACE inhibitor. Use of the factorial design and quadratic response surface models to evaluate the fosinopril and hydrochlorothiazide combination therapy in hypertension. Response to Antihypertensive Therapy in Older Patients With Sustained and Nonsustained Systolic Hypertension Comparison of the Effects of Antihypertensive Agents on Central Blood Pressure and Arterial Stiffness in Isolated Systolic Hypertension Antihypertensive effects of two fixed-dose combinations of losartan and hydrochlorothiazide versus hydrochlorothiazide monotherapy in subjects with ambulatory systolic hypertension. Factorial antihypertensive study of an extended-release metoprolol and hydrochlorothiazide combination. Aliskiren alone or with other antihypertensives in the elderly with borderline and stage 1 hypertension: the APOLLO trial. Reserpine plus hydrochlorothiazide and sotalol plus hydrochlorothiazide in Black and Indian hypertensive patients. Antihypertensive effects of amlodipine and hydrochlorothiazide in elderly patients with ambulatory hypertension. Beta-blocker/thiazide combination for treatment of hypertensive children: a randomized double-blind, placebo-controlled trial. Antihypertensive therapy in older patients with isolated systolic hypertension: the Syst-Eur experience in general practice Effect of diuretic-based antihypertensive treatment on cardiovascular disease risk in older diabetic patients with isolated systolic hypertension. Systolic Hypertension in the Elderly Program Cooperative Research Group. Blood-Pressure Lowering in Intermediate-Risk Persons without Cardiovascular Disease. Effects of immediate versus delayed antihypertensive therapy on outcome in the Systolic Hypertension in Europe Trial Nitrendipine in older patients with isolated systolic hypertension: second progress report on the SYST-EUR trial.
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 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 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 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 Background The goal of the present study was to assess the effect of antihypertensive therapy on clinic ( CBP ) and ambulatory ( ABP ) blood pressures , on ECG voltages , and on the incidence of stroke and cardiovascular events in older patients with sustained and nonsustained systolic hypertension . Methods and Results Patients who were ≥60 years old , with systolic CBP of 160 to 219 mm Hg and diastolic CBP of < 95 mm Hg , were r and omized into the double-blind placebo-controlled Systolic Hypertension in Europe ( Syst-Eur ) Trial . Treatment consisted of nitrendipine , with the possible addition of enalapril , hydrochlorothiazide , or both .  Patients enrolled in the Ambulatory Blood Pressure Monitoring Side Project were classified according to daytime systolic ABP into 1 of 3 subgroups : nonsustained hypertension ( < 140 mm Hg ) , mild sustained hypertension ( 140 to 159 mm Hg ) , and moderate sustained hypertension ( ≥160 mm Hg ) . At baseline , patients with nonsustained hypertension had smaller ECG voltages ( P < 0.001 ) and , during follow-up , a lower incidence of stroke ( P < 0.05 ) and of cardiovascular complications ( P = 0.01 ) than other groups . Active treatment reduced ABP and CBP in patients with sustained hypertension but only CBP in patients with nonsustained hypertension ( P < 0.001 ) . The influence of active treatment on ECG voltages ( P < 0.05 ) and on the incidence of stroke ( P < 0.05 ) and cardiovascular events ( P = 0.06 ) was more favorable than that of placebo only in patients with moderate sustained hypertension . Conclusions Patients with sustained hypertension had higher ECG voltages and rates of cardiovascular complications than did patients with nonsustained hypertension . The favorable effects of active treatment on these outcomes were only statistically significant in patients with moderate sustained hypertension Isolated systolic hypertension is an important risk factor for cardiovascular disease and results primarily from elastic artery stiffening . Although various drug therapies are used to lower peripheral blood pressure ( BP ) in patients with isolated systolic hypertension , the effects of the 4 major classes of antihypertensive agents on central BP , pulse pressure ( PP ) amplification , and arterial stiffness in this condition are not clear . Fifty-nine patients over the age of 60 years with untreated isolated systolic hypertension ( systolic BP ≥140 mm Hg and diastolic BP ≤90 mm Hg ) were r and omly assigned to receive 1 of the following 4 antihypertensive agents : perindopril , atenolol , lercanidipine , or bendrofluazide  . BP was measured using a mercury sphygmomanometer , and augmentation index and carotid-femoral ( aortic ) pulse wave velocity were measured at baseline , after 2 weeks of placebo therapy , and at the end of 10 weeks of active therapy . Peripheral systolic BP and peripheral PP were reduced similarly after treatment with all 4 classes of drug . However , central PP was only reduced significantly by perindopril , lercanidipine , and bendrofluazide , whereas atenolol had no effect . Lercanidipine reduced the augmentation index , whereas atenolol increased it . Aortic pulse wave velocity was not changed by any of the drugs . In summary , despite similar reductions in peripheral systolic and PPs with the 4 classes of drug , changes in central pressure and augmentation index varied . Because central PP and increased wave reflections are considered important risk factors in patients with isolated systolic hypertension , the choice of therapy may be influenced by these findings in the future BACKGROUND The efficacy of losartan ( L ) in combination with hydrochlorothiazide ( HCTZ ) has been demonstrated to reduce blood pressure . However , there are limited data on the effects of L/HCTZ combinations versus HCTZ monotherapies in reducing ambulatory systolic blood pressure . The aim of this study was to compare the effects of these treatment approaches in patients with ambulatory systolic hypertension . METHODS Patients were r and omized to receive L 50 mg ( n = 60 ) or HCTZ 12.5 mg ( n = 60 ) for 6 weeks . Patients were then force-titrated to L 50/HCTZ 12.5 mg and to L 100/HCTZ 25 mg or were sham-titrated to HCTZ 12.5 mg and force-titrated to HCTZ 25 mg , respectively . Clinic and 24-h ambulatory blood pressure ( ABP ) were measured at baseline and after each 6-week treatment period . RESULTS We found that L 50 and HCTZ 12.5 induced significant and similar decreases in clinic and ABP . The combinations of L 50/HCTZ 12.5 and L 100/HCTZ 25 provided significantly greater decreases in clinic and ABP than did HCTZ monotherapies . The L 50/HCTZ 12.5 and L 100/HCTZ 25 combinations provided significant additional decreases in systolic/diastolic ABP during daytime ( -5.3/-2.0 mm Hg ; P < .001 and -5.8/-3.4 mm Hg ; P < .001 ) and the other periods of the 24-h interval compared with the levels achieved by the previous treatment , indicating a clear dose-response relationship . However , increasing the dose of HCTZ from 12.5 mg to 25 mg was not associated with additional ABP reductions . CONCLUSIONS Combinations of L 50/HCTZ 12.5 and L 100/HCTZ 25 provided greater reductions in clinic and ABP than HCTZ monotherapies , with a clear dose-response relationship with regard to ABP . These results support the use of ABP monitoring when assessing the efficacy of antihypertensive therapies BACKGROUND To attain goal blood pressure ( BP ) , many hypertensive patients require combination antihypertensive therapy . Thiazide diuretic/beta-blocker regimens lower BP , and clinical studies indicate that they reduce the risk for cardiovascular consequences of hypertension . Fixed-dose combination tablets can simplify multidrug treatment regimens . METHODS This multicenter , r and omized , double-blind , placebo-controlled , unbalanced factorial study ( N = 1571 ) was design ed to determine whether hydrochlorothiazide ( HCT ) and extended release ( ER ) metoprolol both contribute to an antihypertensive effect .  Hypertensive adults with sitting diastolic BP ( SiDBP ) 95 to 114 mm Hg and systolic BP ( SiSBP ) < 180 mm Hg received one of three hydrochlorothiazide doses ( 6.25 mg , 12.5 mg , or 25 mg ) , one of four ER-metoprolol doses ( 25 mg , 50 mg , 100 mg , 200 mg ) , or one of nine of the combinations or placebo for 8 weeks . RESULTS Blood pressure decreased with all combinations ( P < .001 v placebo ) ; reductions were dose related , ranging from 8.7 to 15.7 mm Hg ( SiDBP ) and 9.7 to 18.9 mm Hg ( SiSBP ) ( model-derived values ) . Reductions with placebo were 5.3 ( SiDBP ) and 4.2 mm Hg ( SiSBP ) . Both active agents contributed to the combination effect ( P = .0015 for SiDBP ; P = .0006 for SiSBP ) . Several low-dose combinations were approximately as effective as high doses of the individual agents ( differences within 1 to 2.5 mm Hg ) . The adverse event discontinuation rate was 2.9 % . Serum potassium decreased and uric acid increased with increasing doses of HCT . CONCLUSIONS Extended-release metoprolol/hydrochlorothiazide is an effective antihypertensive combination that offers additive antihypertensive contributions from both components AIMS We studied the unclear question whether blood pressure ( BP ) lowering reduces cardiovascular disease ( CVD ) in elderly individuals with systolic BP < 160 mm Hg . METHODS AND RESULTS We initiated a r and omized placebo-controlled stratified 2 × 2 factorial clinical trial evaluating the effects of BP lowering in 11 000 elderly individuals with systolic blood pressure ( SBP ) between 130 and 159 mm Hg , for 5 years . Following 5-week active run-in , participants were r and omized to aliskiren ( 300 mg ) or placebo , and to an additional antihypertensive [ hydrochlorothiazide ( 25 mg ) or amlodipine ( 5 mg ) ] , or their respective placeboes . Study was terminated by sponsor after 1759 subjects ( age 72.1 ± 5.2 years , 88 % receiving at least one antihypertensive ) were r and omized and followed for 0.6 year . Study drugs were well tolerated with few serious adverse events during run-in and after r and omization , with no significant differences between treatment groups . By design , three levels of BP reductions were achieved , adjusted mean BP reductions of 3.5/1.7 mm Hg ( P < 0.001 ) by aliskiren , 6.8/3.3 mm Hg ( P < 0.001 ) by hydrochlorothiazide or amlodipine , and 10.3/5.0 mm Hg ( P < 0.001 ) by double therapy compared with placebo . Twenty-five major CVD events occurred . Non-significant trends towards fewer CVD events with greater BP reductions are evident : hazard ratios ( HR ) 0.82 [ 95 % confidence interval ( CI ) : 0.37 - 1.81 ] for 3.5 mm Hg SBP reduction ; HR 0.45 ( 95 % CI : 0.19 - 1.04 ) for 6.8 mm Hg ; and HR 0.25 ( 0.05 - 1.18 ) for 10.3 mm Hg reduction for primary composite of CV death , MI , stroke , or significant heart failure . CONCLUSIONS Sizeable reductions in BP , with potential for substantial CVD reduction , can be safely achieved using combinations of BP drugs in the elderly with normal high and Stage 1 hypertension . CLINICAL TRIAL REGISTRATION NCT01259297 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 Recent studies and authorities have advocated the use of low-dose thiazide diuretics as first-line treatment agents in elderly hypertensives . However , these recommendations were based solely on blood pressure ( BP ) measured in the clinic . The objective of the present 32-week double-blind study was to compare the effects of hydrochlorothiazide ( HCTZ ) and amlodipine ( AML ) in elderly patients with confirmed ambulatory hypertension . After a 4-week placebo washout period , 42 ( 25 men , 17 women ) patients ( mean age , 69 years ) with clinic sitting diastolic BP of 95 to 114 mm Hg and daytime ambulatory diastolic BP of > or = 90 mm Hg were r and omized double-blind to receive AML 5 to 10 mg ( n = 21 ) or HCTZ 12.5 to 25 mg ( n = 21 ) once daily . After 8 weeks of monotherapy , patients in whom clinic diastolic BP remained > or = 90 mm Hg were given combination therapy with the other agent . Amlodipine monotherapy induced significant reductions in clinic , mean 24-h , daytime and sleep systolic/diastolic BPs whereas only clinic BP decreased significantly in patients treated with HCTZ monotherapy . Moreover , 19/21 versus 8/21 patients on AML and HCTZ monotherapies achieved adequate BP control . At the end of the 32-week treatment period , combination therapy in the HCTZ group result ed in statistically significant reductions in clinic as well as in 24-h , daytime and sleep ambulatory BPs that were similar to those observed in the AML monotherapy group . In conclusion , the administration of AML monotherapy induced significant reductions in both clinic and ambulatory BPs in elderly patients whereas only clinic BP was significantly decreased by HCTZ monotherapy . Moreover , the addition of AML to HCTZ in patients inadequately controlled by monotherapy has permitted statistically significant decrements in clinic as well as in ambulatory BP . Consequently , the results of the present study suggest that the use of HCTZ in doses of up to 25 mg daily is inadequate for ambulatory BP control in the elderly despite official recommendations Antihypertensive medications are used extensively in children despite a paucity of r and omized , placebo-controlled trials . This study was among the first r and omized , controlled pediatric antihypertensive medication trials , in which the combination drug bisoprolol fumarate/hydrochlorothiazide ( B/HT ) was compared with placebo . The study comprised a 2-week single-blind placebo screening period , a 6-week double-blind dose titration period , a 4-week double-blind dose maintenance period , and a 2-week double-blind dose-tapering period . One hundred and forty subjects were enrolled to achieve 94 r and omized subjects treated either with B/HT ( n=62 ) or placebo ( n=32 ) . B/HT induced significant reductions compared with placebo for average sitting systolic blood pressure ( SiSBP ) ( 9.3 vs. 4.9 mmHg , P<0.05 ) and sitting diastolic blood pressure ( SiDBP ) ( 7.2 vs. 2.7 mmHg , P<0.05 ) . The placebo-subtracted BP reductions were greater in younger children and those with more-severe baseline hypertension . The percentage of subjects with BP less than the 90th percentile at study completion was 45 % for B/HT and 34 % for placebo ( P = NS ) . Although the study demonstrated that B/HT  reduced BP safely compared with placebo , the large placebo effect and failure of most subjects to achieve target BP control make it uncertain whether B/HT is appropriate first-line therapy for pediatric hypertension , particularly in adolescents with mild-to-moderate BP elevation Background and objective . This interim report from the Syst-Eur trial investigated the level of blood pressure control achieved during the double-blind period in patients followed in general practice s. Methods . In the Syst-Eur trial elderly patients ( 60 years or older ) with isolated systolic hypertension were r and omized to either active or placebo treatment . Active treatment consisted of nitrendipine combined with enalapril and /or hydrochlorothiazide to reduce systolic pressure to Results . This analysis was restricted to patients of general practitioners who had been followed for at least 12 months . The placebo ( N = 204 ) and active treatment ( N = 217 ) groups had similar characteristics at r and omization . At one year , the difference in sitting pressure between the two treatment groups was 10 mmHg systolic and 4 mmHg diastolic . Fewer patients remained on monotherapy in the placebo than in the active treatment group and on placebo the second and third line medications were started earlier . Nitrendipine tablets were discontinued in 10 patients on placebo and in 21 patients assigned to active treatment ( P Conclusions . A significant blood pressure reduction can be achieved and maintained in older patients with isolated systolic hypertension followed by general practitioners . Whether this blood pressure reduction results in a clinical ly meaningful decrease of cardiovascular complications is under investigation . Keywords . Antihypertensive treatment , general practice , isolated systolic hypertension , r and omized clinical trial OBJECTIVE To assess the effect of low-dose , diuretic-based antihypertensive treatment on major cardiovascular disease ( CVD ) event rates in older , non-insulin-treated diabetic patients with isolated systolic hypertension ( ISH ) , compared with nondiabetic patients . DESIGN Double-blind , r and omized , placebo-controlled trial : the Systolic Hypertension in the Elderly Program ( SHEP ) . SETTING Multiple clinical and support centers in the United States . PARTICIPANTS A total of 4736 men and women aged 60 years and older at baseline with ISH ( systolic blood pressure [ BP ] , > or = 160 mm Hg ; diastolic BP , < 90 mm Hg ) at baseline , 583 non-insulin-dependent diabetic patients and 4149 nondiabetic patients ( 4 additional patients not so classifiable were r and omized but not included in these analyses ) . Diabetes mellitus defined as physician diagnosis , taking oral hypoglycemic drugs , fasting glucose level of 7.8 mmol/L or more ( > or = 140 mg/dL ) , or any combination of these characteristics . INTERVENTION The active treatment group received a low dose of chlorthalidone ( 12.5 - 25.0 mg/d ) with a step-up to atenolol ( 25.0 - 50.0 mg/d ) or reserpine ( 0.05 - 0.10 mg/d ) if needed . The placebo group received placebo and any active antihypertensive drugs prescribed by patient 's private physician for persistently high BP . MAIN OUTCOME MEASURES The 5-year rates of major CVD events , nonfatal plus fatal stroke , nonfatal myocardial infa rct ion ( MI ) and fatal coronary heart disease ( CHD ) , major CHD events , and all-cause mortality . RESULTS The SHEP antihypertensive drug regimen lowered BP of both diabetic and nondiabetic patients , with few adverse effects . For both diabetic and nondiabetic patients , all outcome rates were lower for participants r and omized to the active treatment group than for those r and omized to the placebo group . Thus , 5-year major CVD rate was lower by 34 % for active treatment compared with placebo , both for diabetic patients ( 95 % confidence interval [ CI ] , 6%-54 % ) and nondiabetic patients ( 95 % CI , 21%-45 % ) . Absolute risk reduction with active treatment compared with placebo was twice as great for diabetic vs nondiabetic patients ( 101/1000 vs 51/1000 r and omized participants at the 5-year follow-up ) , reflecting the higher risk of diabetic patients . CONCLUSION Low-dose diuretic-based ( chlorthalidone ) treatment is effective in preventing major CVD events , cerebral and cardiac , in both non-insulin-treated diabetic and nondiabetic older patients with ISH BACKGROUND Antihypertensive therapy reduces the risk of cardiovascular events among high-risk persons and among those with a systolic blood pressure of 160 mm Hg or higher , but its role in persons at intermediate risk and with lower blood pressure is unclear . METHODS In one comparison from a 2-by-2 factorial trial , we r and omly assigned 12,705 participants at intermediate risk who did not have cardiovascular disease to receive either c and esartan at a dose of 16 mg per day plus hydrochlorothiazide at a dose of 12.5 mg per day or placebo . The first co primary outcome was the composite of death from cardiovascular causes , nonfatal myocardial infa rct ion , or nonfatal stroke ; the second co primary outcome additionally included resuscitated cardiac arrest , heart failure , and revascularization . The median follow-up was 5.6 years . RESULTS The  mean blood pressure of the participants at baseline was 138.1/81.9 mm Hg ; the decrease in blood pressure was 6.0/3.0 mm Hg greater in the active-treatment group than in the placebo group . The first co primary outcome occurred in 260 participants ( 4.1 % ) in the active-treatment group and in 279 ( 4.4 % ) in the placebo group ( hazard ratio , 0.93 ; 95 % confidence interval [ CI ] , 0.79 to 1.10 ; P=0.40 ) ; the second co primary outcome occurred in 312 participants ( 4.9 % ) and 328 participants ( 5.2 % ) , respectively ( hazard ratio , 0.95 ; 95 % CI , 0.81 to 1.11 ; P=0.51 ) . In one of the three prespecified hypothesis-based subgroups , participants in the subgroup for the upper third of systolic blood pressure ( > 143.5 mm Hg ) who were in the active-treatment group had significantly lower rates of the first and second co primary outcomes than those in the placebo group ; effects were neutral in the middle and lower thirds ( P=0.02 and P=0.009 , respectively , for trend in the two outcomes ) . CONCLUSIONS Therapy with c and esartan at a dose of 16 mg per day plus hydrochlorothiazide at a dose of 12.5 mg per day was not associated with a lower rate of major cardiovascular events than placebo among persons at intermediate risk who did not have cardiovascular disease . ( Funded by the Canadian Institutes of Health Research and AstraZeneca ; Clinical Trials.gov number , NCT00468923 . ) Background To assess the impact of immediate versus delayed antihypertensive treatment on the outcome of older patients with isolated systolic hypertension  , we extended the double-blind placebo-controlled Systolic Hypertension in Europe ( Syst-Eur ) trial by an open-label follow-up study lasting 4 years . Methods The Syst-Eur trial included 4695 r and omized patients with minimum age of 60 years and an untreated blood pressure of 160–219 mmHg systolic and below 95 mmHg diastolic . The double-blind trial ended after a median follow-up of 2.0 years ( range 1–97 months ) . Of 4409 patients still alive , 3517 received open-label treatment consisting of nitrendipine ( 10–40 mg daily ) with the possible addition of enalapril ( 5–20 mg daily ) , hydrochlorothiazide ( 12.5–25 mg daily ) , or both add-on drugs .  Non- participants ( n = 892 ) were also followed up . Results Median follow-up increased to 6.1 years . Systolic pressure decreased to below 150 mmHg ( target level ) in 2628 participants ( 75.0 % ) . During the 4-year open-label follow-up , stroke and cardiovascular complications occurred at similar frequencies in patients formerly r and omized to placebo and those continuing active treatment . These rates were similar to those previously observed in the active-treatment group during the double-blind trial . Considering the total follow-up of 4695 r and omized patients , immediate compared with delayed antihypertensive treatment reduced the occurrence of stroke and cardiovascular complications by 28 % ( P = 0.01 ) and 15 % ( P = 0.03 ) , respectively , with a similar tendency for total mortality ( 13 % , P = 0.09 ) . In 492 diabetic patients , the corresponding estimates of long-term benefit ( P < 0.02 ) were 60 , 51 and 38 % , respectively . Conclusions Antihypertensive treatment can achieve blood pressure control in most older patients with isolated systolic hypertension . Immediate compared with delayed treatment prevented 17 strokes or 25 major cardiovascular events per 1000 patients followed up for 6 years . These findings underscore the necessity of early treatment of isolated systolic hypertension This report from the double-blind placebo-controlled SYST-EUR trial investigated whether modern antihypertensive drugs are suitable for maintaining long-term BP control in older ( > or = 60 years of age ) subjects with isolated systolic hypertension ( SBP 160 - 219 mmHg and DBP < 95 mmHg ) . Active treatment consisted of nitredipine ( 10 - 40 mg/day ) with the possible addition of enalapril ( 5 - 20 mg/day ) and hydrochlorothiazide ( 12.5 - 25 mg/day ) , if necessary to reduce SBP to < 150 mmHg and by > or = 20 mmHg . Matching placebos were used in the control group . This analysis was restricted to 18 months of follow-up . The placebo ( n = 456 ) and active treatment ( n = 485 ) groups had similar characteristics at r and omisation ( sitting pressure 176/85 mmHg ; age 73 years ) .  SBP fell ( P < 0.001 ) on average 10 mmHg more on active treatment than on placebo and DBP 4 mmHg more . Fewer patients remained on monotherapy in the placebo than in the active treatment group ( P < 0.001 ) ; on placebo the second and third line medications were started earlier ( P < 0.001 ) . Nitrendipine tablets were discontinued in nine patients on placebo and in 29 patients assigned to active treatment ( P < 0.001 ) . In conclusion , a significant BP reduction can be achieved and maintained in older patients with isolated systolic hypertension treated with a calcium antagonist ( associated with a converting-enzyme inhibitor and a thiazide , where necessary ) . Whether this BP reduction results in a clinical ly meaningful decrease of cardiovascular complications is under investigation
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 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 .