Combination of a thiazide, a vasodilator and reserpine compared with methyldopa plus hydrochlorothiazide in the treatment of hypertension in Zimbabwe. Reserpine plus hydrochlorothiazide and sotalol plus hydrochlorothiazide in Black and Indian hypertensive patients. Comparison of the Effects of Antihypertensive Agents on Central Blood Pressure and Arterial Stiffness in Isolated Systolic Hypertension Benazepril plus amlodipine or hydrochlorothiazide for hypertension in high-risk patients. Low-dose reserpine/thiazide combination in first-line treatment of hypertension: efficacy and safety compared to an ACE inhibitor. Antihypertensive therapy in older patients with isolated systolic hypertension: the Syst-Eur experience in general practice A randomised crossover comparison of reserpine and sustained-release nifedipine in hypertension. Factorial antihypertensive study of an extended-release metoprolol and hydrochlorothiazide combination. Blood-Pressure Lowering in Intermediate-Risk Persons without Cardiovascular Disease. Use of the factorial design and quadratic response surface models to evaluate the fosinopril and hydrochlorothiazide combination therapy in hypertension. 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. The prevention of dementia with antihypertensive treatment: new evidence from the Systolic Hypertension in Europe (Syst-Eur) study. Aliskiren alone or with other antihypertensives in the elderly with borderline and stage 1 hypertension: the APOLLO trial. 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. Antihypertensive effects of two fixed-dose combinations of losartan and hydrochlorothiazide versus hydrochlorothiazide monotherapy in subjects with ambulatory systolic hypertension. Treatment of isolated systolic hypertension in the elderly: further evidence from the systolic hypertension in Europe (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 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 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 optimal combination drug therapy for hypertension is not established , although current U.S. guidelines recommend inclusion of a diuretic . We hypothesized that treatment with the combination of an angiotensin-converting-enzyme ( ACE ) inhibitor and a dihydropyridine calcium-channel blocker would be more effective in reducing the rate of cardiovascular events than treatment with an ACE inhibitor plus a thiazide diuretic . METHODS In a r and omized , double-blind trial , we assigned 11,506 patients with hypertension who were at high risk for cardiovascular events to receive treatment with either benazepril plus amlodipine or benazepril plus hydrochlorothiazide . The primary end point was the composite of death from cardiovascular causes , nonfatal myocardial infa rct ion , nonfatal stroke , hospitalization for angina , resuscitation after sudden cardiac arrest , and coronary revascularization . RESULTS The baseline characteristics of the two groups were similar . The trial was terminated early after a mean follow-up of 36 months , when the boundary of the prespecified stopping rule was exceeded . Mean blood pressures after dose adjustment were 131.6/73.3 mm Hg in the benazepril-amlodipine group and 132.5/74.4 mm Hg in the benazepril-hydrochlorothiazide group . There were 552 primary - outcome events in the benazepril-amlodipine group ( 9.6 % ) and 679 in the benazepril-hydrochlorothiazide group ( 11.8 % ) , representing an absolute risk reduction with benazepril-amlodipine therapy of 2.2 % and a relative risk reduction of 19.6 % ( hazard ratio , 0.80 , 95 % confidence interval [ CI ] , 0.72 to 0.90 ; P<0.001 ) . For the secondary end point of death from cardiovascular causes , nonfatal myocardial infa rct ion , and nonfatal stroke , the hazard ratio was 0.79 ( 95 % CI , 0.67 to 0.92 ; P=0.002 ) . Rates of adverse events were consistent with those observed from clinical experience with the study drugs . CONCLUSIONS The benazepril-amlodipine combination was superior to the benazepril-hydrochlorothiazide combination in reducing cardiovascular events in patients with hypertension who were at high risk for such events . ( Clinical Trials.gov number , NCT00170950 . 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 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 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 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 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 . ) 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 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 After the double-blind , placebo-controlled Systolic Hypertension in Europe ( Syst-Eur ) trial ended in February 1997 , r and omized patients were offered active study medication for a further period of observation . OBJECTIVE To refine the estimates of the long-term effects of antihypertensive therapy on the incidence of dementia . METHODS Eligible patients had no dementia and were at least 60 years old . Their systolic blood pressure at entry was 160 to 219 mm Hg , with diastolic blood pressure below 95 mm Hg .  Antihypertensive therapy was started immediately after r and omization in the active treatment group , but only after termination of the double-blind trial in the control patients . Treatment consisted of nitrendipine ( 10 - 40 mg/d ) , with the possible addition of enalapril maleate ( 5 - 20 mg/d ) , hydrochlorothiazide ( 12.5 - 25 mg/d ) , or both add-on drugs . RESULTS Median follow-up increased from 2.0 years in the double-blind trial to 3.9 years overall . The incidence of dementia doubled from 32 to 64 cases , 41 of whom had Alzheimer disease . Throughout follow-up , systolic/diastolic blood pressure was 7.0/3.2 mm Hg higher in the 1417 control patients than in the 1485 subjects r and omized to active treatment . At the last examination , the blood pressure difference was still 4.2/2.9 mm Hg ; 48.1 % , 26.4 % , and 11.4 % of the control patients were taking nitrendipine , enalapril , and /or hydrochlorothiazide , whereas in the active treatment group these proportions were 70.2 % , 35.4 % , and 18.4 % , respectively . Compared with the controls , long-term antihypertensive therapy reduced the risk of dementia by 55 % , from 7.4 to 3.3 cases per 1000 patient-years ( 43 vs 21 cases , P<.001 ) . After adjustment for sex , age , education , and entry blood pressure , the relative hazard rate associated with the use of nitrendipine was 0.38 ( 95 % confidence interval , 0.23 - 0.64 ; P<.001 ) . Treatment of 1000 patients for 5 years can prevent 20 cases of dementia ( 95 % confidence interval , 7 - 33 ) . CONCLUSION The extended follow-up of Syst-Eur patients reinforces the evidence that blood pressure-lowering therapy initiated with a long-acting dihydropyridine protects against dementia in older patients with systolic hypertension 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 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 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 The Systolic Hypertension in Europe ( Syst-Eur ) study investigated whether antihypertensive treatment could decrease the risk of cardiovascular complications in elderly patients with isolated systolic hypertension . Patients > or = 60 years were r and omly assigned to treatment with the dihydropyridine calcium antagonist nitrendipine ( n = 2,398 ) , with the addition of enalapril and hydrochlorothiazide if needed , or to matching placebo  ( n = 2,297 ) . In the intent-to-treat analysis , the between-group difference in blood pressure was 10.1/4.5 mm Hg ( p < 0.001 ) . Active treatment decreased the total incidence of stroke ( the primary endpoint ) by 42 % ( p = 0.003 ) , of all cardiac endpoints by 26 % ( p = 0.03 ) , and of all cardiovascular endpoints combined by 31 % ( p < 0.001 ) . Cardiovascular mortality was somewhat lower with active treatment ( -27 % , p = 0.07 ) ; all-cause mortality was not significantly different ( -14 % ; p = 0.22 ) . For total ( p = 0.009 ) and cardiovascular ( p = 0.09 ) mortality , the benefit of antihypertensive treatment weakened with advancing age and for total mortality it decreased with lower systolic blood pressure at entry ( p = 0.05 ) . The benefits of active treatment were not independently related to gender or to the presence of cardiovascular complications at entry . Antihypertensive therapy was at least as effective in patients with diabetes as in those without diabetes at entry . Further analyses suggested benefit in patients who were taking nitrendipine as monotherapy . Per- protocol analysis largely confirmed the intent-to-treat results . Active treatment decreased all strokes by 44 % ( p = 0.004 ) , all cardiac endpoints by 26 % ( p = 0.05 ) , and all cardiovascular endpoints by 32 % ( p < 0.001 ) . Total mortality was decreased by 26 % ( p = 0.05 ) , but the similar reduction in cardiovascular mortality did not reach significance in this analysis . It is concluded that stepwise antihypertensive drug treatment starting with nitrendipine improves prognosis in elderly patients with isolated systolic hypertension
Due to significant heterogeneity across trials , a significant effect in diastolic blood pressure ( DBP ) , mean arterial pressure ( MAP ) , and heart rate ( HR ) could not be found .
The SBP effects were achieved with 0.5 mg/day or greater .
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 and /or diastolic blood pressure > /=90 mmHg ) .
R and omised controlled trials have been carried out to investigate the evidence for these agents .
There is , for example , strong RCT evidence that thiazides reduce mortality and morbidity .
Reserpine has been used as a second-line therapy in some of those trials .
However , the dose-related blood pressure reduction with this agent is not known .
OBJECTIVES To investigate the dose-related effect of reserpine on blood pressure , heart rate and withdrawals due to adverse events .