Calcium channel blockers and cardiac mortality in the treatment of hypertension: a report from the Department of Health Hypertension Care Computing Project (DHCCP) Outcomes in hypertensive black and nonblack patients treated with chlorthalidone, amlodipine, and lisinopril. South African hypertension guideline 2011. Angiotensin-converting enzyme inhibitors, calcium channel blockers, and breast cancer. Calcium-channel blockers and cognitive function in elderly people: results from the Canadian Study of Health and Aging. An angiotensin II receptor blocker–calcium channel blocker combination prevents cardiovascular events in elderly high-risk hypertensive patients with chronic kidney disease better than high-dose angiotensin II receptor blockade alone 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). Cardiovascular risk and risk factors in a randomized trial of treatment based on the beta-blocker oxprenolol: the International Prospective Primary Prevention Study in Hypertension (IPPPSH). The IPPPSH Collaborative Group. The effects of increasing calcium channel blocker dose vs. adding a diuretic to treatment regimens for patients with uncontrolled hypertension Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT): Practical Implications Blood pressure 1 year after stroke: the need to optimize secondary prevention. Clinical Events in High-Risk Hypertensive Patients Randomly Assigned to Calcium Channel Blocker Versus Angiotensin-Converting Enzyme Inhibitor in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial Use of calcium channel blockers is associated with better cognitive performance in older hypertensive patients with subjective memory complaints Comparison of two calcium blockers on hemodynamics, left ventricular mass, and coronary vasodilatory in advanced hypertension. The risk of myocardial infarction associated with antihypertensive drug therapies. Background and design of the new U.S. trial on diet and drug treatment of "mild" hypertension (TOMHS). Effects of calcium-channel blockade in older patients with diabetes and systolic hypertension. Systolic Hypertension in Europe Trial Investigators.
Objective : A case control study has reported a 60 % higher risk of myocardial infa rct ion in hypertensives treated with a calcium channel blocker ( CCB ) . We examined the Department of Health Hypertension Care Computing Project ( DHCCP ) data to see if we could confirm or refute this suggestion . Design : Two case control studies , matched and unmatched , plus two longitudinal studies from 1 year of presentation , one for all subjects given a CCB  for more than 1 year compared with those not given this drug , and the second comparing survival on the different drugs initially given between 3 and 12 months of follow-up . Subjects : A total of 9328 subjects were included in the analyses and 2154 died . Of these , 6406 received one or more of the following index drugs : 26 % a calcium channel blocker ( CCB ) ; 84 % a diuretic ; 29 % alpha methyldopa ; 12 % a beta-blocker ( BB ) ; and 11 % an angiotensin-converting enzyme ( ACE ) inhibitor . The CCBs were nifedipine , diltiazem or verapamil . Results : In the case control studies a group given diuretics ± other treatments ( but not including one of the index drugs ) provided a reference group with a relative risk ( RR ) of 1.0 . In the matched case control study the adjusted RR for a CCB  without a diuretic was 1.32 ( 95 % CI 0.64–2.70 ) for IHD mortality and 1.05 ( 95 % CI 0.60–1.84 ) for cardiovascular mortality . Similar results were observed for methyldopa , BBs and ACE inhibitors . The results in the unmatched case control analysis were also similar . The longitudinal study comparing all those treated for over 1 year with a CCB with all other treatments showed a RR for total mortality of 1.03 ( 95 % CI 0.85–1.25 ) . The longitudinal study of total mortality according to treatment initiated at 3–12 months found results of a similar magnitude for CCBs , methyldopa and BBs . Conclusions : The reference diuretic group had less severe cardiovascular disease than other groups . Treatment with a CCB , BB or methyldopa was associated with an excess mortality in comparison with this reference group . The excess was similar in the different drug groups CONTEXT Few cardiovascular outcome data are available for blacks with hypertension treated with angiotensin-converting enzyme ( ACE ) inhibitors or calcium channel blockers ( CCBs ) . OBJECTIVE To determine whether an ACE inhibitor or CCB is superior to a thiazide-type diuretic in reducing cardiovascular disease ( CVD ) incidence in racial subgroups . DESIGN , SETTING , AND PARTICIPANTS Prespecified subgroup analysis of ALLHAT , a r and omized , double-blind , active-controlled , clinical outcome trial conducted between February 1994 and March 2002 in 33,357 hypertensive US and Canadian patients aged 55 years or older ( 35 % black ) with at least 1 other cardiovascular risk factor . INTERVENTIONS Antihypertensive regimens initiated with a CCB ( amlodipine ) or an ACE inhibitor ( lisinopril ) vs a thiazide-type diuretic ( chlorthalidone ) . Other medications were added to achieve goal blood pressures ( BPs ) less than 140/90 mm Hg . MAIN OUTCOME MEASURES The primary outcome was combined fatal coronary heart disease ( CHD ) or nonfatal myocardial infa rct ion ( MI ) , analyzed by intention-to-treat . Secondary outcomes included all-cause mortality , stroke , combined CVD ( CHD death , nonfatal MI , stroke , angina , coronary revascularization , heart failure [ HF ] , or peripheral vascular disease ) , and end-stage renal disease . RESULTS No significant difference was found between treatment groups for the primary CHD outcome in either racial subgroup . For amlodipine vs chlorthalidone only , HF was the only prespecified clinical outcome that differed significantly ( overall : relative risk [ RR ] , 1.37 ; 95 % confidence interval [ CI ] , 1.24 - 1.51 ; blacks : RR , 1.46 ; 95 % CI , 1.24 - 1.73 ; nonblacks : RR , 1.32 ; 95 % CI , 1.17 - 1.49 ; P<.001 for each comparison ) with no difference in treatment effects by race ( P = .38 for interaction ) . For lisinopril vs chlorthalidone , results differed by race for systolic BP ( greater decrease in blacks with chlorthalidone ) , stroke , and combined CVD outcomes ( P<.001 , P = .01 , and P = .04 , respectively , for interactions ) . In blacks and nonblacks , respectively , the RRs for stroke were 1.40 ( 95 % CI , 1.17 - 1.68 ) and 1.00 ( 95 % CI , 0.85 - 1.17 ) and for combined CVD were 1.19 ( 95 % CI , 1.09 - 1.30 ) and 1.06 ( 95 % CI , 1.00 - 1.13 ) . For HF , the RRs were 1.30 ( 95 % CI , 1.10 - 1.54 ) and 1.13 ( 95 % CI , 1.00 - 1.28 ) , with no significant interaction by race . Time-dependent BP adjustment did not significantly alter differences in outcome for lisinopril vs chlorthalidone in blacks . CONCLUSIONS In blacks and nonblack subgroups , rates were not lower in the amlodipine or lisinopril groups than in the chlorthalidone group for either the primary CHD or any other prespecified clinical outcome , and diuretic-based treatment result ed in the lowest risk of heart failure . While the improved outcomes with chlorthalidone were more pronounced for some outcomes in blacks than in nonblacks , thiazide-type diuretics remain the drugs of choice for initial therapy of hypertension in both black and nonblack hypertensive patients OUTCOMES Extensive data from r and omised controlled trials have shown the benefit of treating hypertension . The target blood pressure ( BP ) for antihypertensive management is systolic < 140 mmHg and diastolic < 90 mmHg with minimal or no drug side-effects ; however , stricter BP control is required for patients with end-organ damage , co-existing risk factors and co-morbidity , e.g. diabetes mellitus . The reduction of BP in the elderly and in those with severe hypertension should be achieved gradually over 1 month . Co-existent risk factors should also be controlled . BENEFITS Benefits of management include reduced risks of stroke , cardiac failure , chronic kidney disease and coronary heart disease . RECOMMENDATIONS The correct BP measurement procedure is described , and evaluation of cardiovascular risk factors and recommendations for antihypertensive therapy are stipulated . The total cardiovascular disease risk profile should be determined for all patients to inform management strategies . Lifestyle modification and patient education are cornerstones in the management of every patient . Major indications , pre caution s and contra-indications to each recommended antihypertensive drug are listed . Combination therapy should be considered ab initio if the BP is ≥ 20/10 mmHg . First-line drug therapy for uncomplicated hypertension includes low-dose thiazide-like diuretics , calcium channel blockers ( CCBs ) or angiotensin-converting enzyme inhibitors ( ACE-Is ) ( or ARBs - angiotensin II receptor blockers ) . If the target BP is not obtained , a second antihypertensive should be added from the aforementioned list . If the target BP is still not met , the third remaining antihypertensive agent should be used . In black patients  either thiazide-like diuretics or CCBs can be used initially , because response rates are better than with ACE-Is or β-blockers . In treating resistant hypertension , a central ly acting drug , vasodilator , α-blocker , spironolactone or β-locker should be added . This guideline includes management of specific situations , i.e. hypertensive emergency and urgency , severe hypertension with target organ damage , hypertension in diabetes mellitus , resistant hypertension , fixed drug combinations , new trials in hypertension , and interactions of antihypertensive agents with other drugs . VALIDITY The guideline was developed by the Southern African Hypertension Society BACKGROUND The use of angiotensin-converting enzyme ( ACE ) inhibitors has been linked to a decreased risk of developing cancer , and longer-term use of calcium channel blockers ( CCBs ) has been associated with an increased risk of developing cancer in general and breast cancer in particular . METHODS Using data from the General Practice Research Data base , we conducted a large case-control analysis . Previous exposure to ACE inhibitors , CCBs , and beta-blockers was compared between 3706 postmenopausal women who were diagnosed with incident breast cancer between 1992 and 1997 and 14155 matched-control women . RESULTS Compared with nonusers of antihypertensive drugs , women who used ACE inhibitors ( odds ratio [ OR ] , 1.0 ; 95 % confidence interval [ CI ] , 0.7 - 1.5 ) , CCBs ( OR , 0.9 ; 95 % CI , 0.7 - 1.2 ) , or beta-blockers ( OR , 1.0 ; 95 % CI , 0.8 - 1.2 ) for 5 or more years were not at an increased or decreased risk of developing breast cancer ( adjusted for smoking and body mass index [ calculated as weight in kilograms divided by the square of height in meters ] ) . The risk of breast cancer did not differ between users of different ACE inhibitors or different CCBs ( dihydropyridines , diltiazem hydrochloride , and verapamil hydrochloride ) or between users of short-acting ( OR , 1.0 ; 95 % CI , 0.7 - 1.4 ) or sustained-release ( OR , 1.0 ; 95 % CI , 0.8 - 1.3 ) nifedipine preparations . CONCLUSION The findings of this large case-control analysis do not support the hypothesis that longer-term use of ACE inhibitors or CCBs affects the risk of developing breast cancer BACKGROUND Concern has been raised about the potential for adverse cognitive effects associated with the use of calcium-channel blockers ( CCBs ) in older people . This study was undertaken to examine prospect ively the association between the use of these and other antihypertensive drugs and cognitive function . METHODS The authors examined data from the Canadian Study of Health and Aging ( CSHA ) , a population -based , prospect i ve 5-year investigation of the epidemiology of dementia and other health problems in Canadians 65 years of age and older . The risk of cognitive decline , as indicated by a decline in performance on the Modified Mini-Mental State ( 3MS ) examination over the 5-year period , was assessed in relation to the use of antihypertensive and diuretic drugs by 205 subjects with a history of hypertension and no evidence of dementia at baseline . RESULTS The proportion of subjects whose cognitive performance declined over the study period was significantly higher in the group using CCBs than in the group using other antihypertensive agents ( 75 % v. 59 % ) . The adjusted odds ratio ( OR ) for a significant decline in cognitive performance ( defined as a decrease in 3MS score of 10 points or more ) was 2.28 ( 95 % confidence interval [ CI ] 1.12 - 4.66 ) for subjects using CCBs . The adjusted ORs ( and 95 % CIs ) for cognitive decline in subjects using selected antihypertensive agents or diuretics relative to those exposed to beta-blockers were as follows : angiotensin-converting-enzyme inhibitor , OR 1.36 ( 95 % CI 0.41 - 4.55 ) ; diuretic or other antihypertensive drug , OR 1.45 ( 95 % CI 0.51 - 4.14 ) ; dihydropyridine CCB ( nifedipine ) , OR 1.94 ( 95 % CI 0.52 - 7.27 ) and non-dihydropyridine CCB ( diltiazem or verapamil ) , OR 3.72 ( 95 % CI 1.22 - 11.36 ) . INTERPRETATION Older people taking CCBs were significantly more likely than those using other agents to experience cognitive decline . These findings are consistent with the results of previous cross-sectional research and emphasize the need for further trials to examine the associations between CCB use , blood pressure and cognitive impairment in elderly patients The OSCAR study was a multicenter , prospect i ve r and omized open-label blinded end-point study of 1164 Japanese elderly hypertensive patients comparing the efficacy of angiotensin II receptor blocker ( ARB ) uptitration to an ARB plus calcium channel blocker ( CCB ) combination . In this prospect i ve study , we performed prespecified subgroup analysis according to baseline estimated glomerular filtration rate ( eGFR ) with chronic kidney disease ( CKD ) defined as an eGFR < 60 ml/min per 1.73 m2 .  Blood pressure was lower in the combined therapy than in the high-dose ARB cohort in both groups with and without CKD . In patients with CKD , significantly more primary events ( a composite of cardiovascular events and noncardiovascular death ) occurred in the high-dose ARB group than in the combination group ( 30 vs. 16 , respectively , hazard ratio 2.25 ) . Significantly more cerebrovascular and more heart failure events occurred in the high-dose ARB group than in the combination group . In patients without CKD , however , the incidence of primary events was similar between the two treatments . The treatment-by-subgroup interaction was significant . Allocation to the high-dose ARB was a significant independent prognostic factor for primary events in patients with CKD . Thus , the ARB plus CCB combination conferred greater benefit in prevention of cardiovascular events in patients with CKD compared with high-dose ARB alone . Our findings provide new insight into the antihypertensive strategy for elderly hypertensive patients with CKD 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 Myocardial infa rct ion , sudden cardiac death , cerebrovascular accidents , blood pressure control and treatment tolerability were studied in a r and omized double-blind trial conducted in 6357 men and women aged 40 - 64 years with uncomplicated essential hypertension ( diastolic blood pressures 100 - 125 mmHg ) . At the start of the trial 3185 patients received treatment based on a beta-blocker ( oxprenolol )  , while in the remaining 3172 placebo replaced oxprenolol .  Supplementary drugs , excluding beta-blockers , were used as necessary in both treatment groups , with the aim of reducing diastolic pressure to 95 mmHg or less . Patients were followed for 3 - 5 years , a total of 25 651 patient years at risk . In most respects the two groups fared equally well ; sudden death ( relative risk [ RR ] 1.08 ; 95 % confidence interval [ Cl ] 0.68 and 1.72 ) , myocardial infa rct ion ( RR 0.83 ; Cl 0.59 and 1.16 ) and cerebrovascular accident ( RR 0.97 ; Cl 0.64 and 1.47 ) rates were similar . Beta-blocker based therapy was associated with significantly lower average blood pressures , earlier ECG normalization , less hypokalaemia and fewer withdrawals from double-blind treatment for uncontrolled hypertension . Doctor-elicited and patient-assessed unwanted effects demonstrated overall good tolerability . In smokers the cardiac event rate was doubled . We propose that beta-blocker treatment effects depend on smoking status , with a significant interaction benefiting non-smoking men . Lower blood pressures during treatment were associated with substantially lower rates for cardiac as well as cerebrovascular events . Proportional hazards analysis also underlines the importance of other cardiovascular risk factors . The IPPPSH stresses the need for a comprehensive approach to the management of blood pressure and other risk factors in hypertensive patients In patients with insufficient blood pressure ( BP ) control , despite using a combination regimen containing an angiotensin receptor blocker and a calcium channel blocker ( CCB ) , whether a greater dose of CCB or adding a diuretic is more effective at lowering BP remains unclear . We conducted a multicenter r and omized clinical trial to compare the efficacy of switching from the daily administration of a single-pill fixed-dose combination of irbesartan ( 100 mg ) and amlodipine ( 5 mg ) to irbesartan ( 100 mg ) with an increased dose of amlodipine ( 10 mg ) ( HD group , n=62 ) or irbesartan ( 100 mg ) and amlodipine ( 5 mg ) with 1 mg of indapamide ( D group , n=63 ) in patients with poorly controlled hypertension .  BP measured at home was monitored by a physician using a telemonitoring system . Between the HD and D groups , no significant differences were observed in morning home BP changes ( mean reduction of systolic/diastolic BP , 1.7/0.9 mmHg ; 95 % confidence intervals , −2.4 to 5.7/−1.4 to 3.2 ; P=0.19/0.37 ) , achievement rate of target BP ( 45.2 % vs. 42.9 % , P=0.80 ) , BP variability independent of the mean ( P⩾0.74 ) , other variability indices ( P⩾0.55 ) and time to stabilization , which was calculated using a fitted analysis ( 13.1 days vs. 11.4 days , P=0.99 ) . Although a significant increase in serum uric acid was observed in the D group ( P<0.0001 ) , neither clinical ly relevant abnormal laboratory test results nor critical BP changes were observed throughout the trial period . Both antihypertensive drug combination strategies were effective treatment options . Further investigation is required to determine the appropriate use of both therapies based on the various pathologies associated with hypertension The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial ( ALLHAT ) , sponsored by the National Heart , Lung , and Blood Institute ( NHLBI ) , is the largest outcome trial of antihypertensive treatment ever carried out and the only large blood pressure ( BP ) trial to be carried out in a US population in the past decade.1 The rationale for ALLHAT , which was design ed in the early 1990s , was the urgent need to determine which of the several classes of antihypertensive drugs that had been developed and released for clinical use was most effective in preventing coronary heart disease ( CHD ) , defined as fatal CHD and nonfatal myocardial infa rct ion.2 The only r and omized trials that had previously compared representatives of the antihypertensive drug classes , the Department of Veterans Affairs Cooperative Study Group on Antihypertensive Agents3 and the Treatment of Mild Hypertension Study (TOMHS),4 showed BP reductions with all classes but were not powered to evaluate CHD outcomes . Further , prior outcome trials had shown that the reduction in CHD event rates with antihypertensive treatment was less than expected based on epidemiologic data .5 Adverse effects of study drugs , particularly diuretics , including hypokalemia , hypomagnesemia , hyperuricemia , hyperlipidemia , insulin resistance , and ventricular ectopic activity , had been adduced to account for the disappointing outcomes of earlier trials by off setting the beneficial effects of BP reduction.6,7 To further complicate the picture , benefits beyond BP reduction had been attributed to some antihypertensive drug classes , ie , improved survival and reduced morbidity in persons with heart failure or left ventricular dysfunction treated with angiotensin-converting enzyme ( ACE ) inhibitors8–10 and improved insulin sensitivity and lipid profiles with α-blocker treatment.11 In contrast , another antihypertensive drug class , the dihydropyridine calcium channel blockers ( CCBs ) , had been associated with unfavorable outcomes in patients with acute myocardial infa rct ion or unstable angina.12 There were no data Lowering blood pressure ( BP ) in stroke survivors reduces the risk of recurrent stroke . We tested the hypothesis that a nurse-led nonpharmacologic intervention would lower the BP of participants in an intervention group compared with a control group . A total of 349 patients who had sustained acute stroke or transient ischemic attack were r and omly assigned to either usual care or to 4 home visits by a nurse . During the visits , the nurse measured and recorded BP and provided individually tailored counseling on a healthy lifestyle . A total of 303 patients completed the 1-year follow up . No change in systolic BP was noted in either the intervention group or the control group . Because of an increase in diastolic BP in the control group ( P = .03 ) , a difference in mean diastolic BP between the 2 groups was found at follow-up ( P = .007 ) . Mean BP at follow-up was 139/82 mm Hg in the intervention group and 142/86 mm Hg in the control group . Linear regression analysis demonstrated that BP at the point of discharge was the strongest predictor of BP 1 year later ( P < .0001 ) . The proportion of patients on antihypertensive medication increased in the intervention group ( P = .002 ) . Patients were compliant with antihypertensive therapy , and 92 % of the hypertensive patients in the intervention group followed the advice to see a general practitioner ( GP ) for BP checkups . At follow-up , 187 patients ( 62 % ) were hypertensive , with no difference in the rate of hypertension seen between the groups . Our data indicate that home visits by nurses did not result in a lowering of BP . Patients complied with antihypertensive therapy and GP visits in the case of hypertension . Nonetheless , the majority of patients were hypertensive at the 1-year follow up The Antihypertensive and Lipid-Lowering treatment to prevent Heart Attack Trial ( ALLHAT ) provides a unique opportunity to compare the long-term relative safety and efficacy of angiotensin-converting enzyme inhibitor and calcium channel blocker – initiated therapy in older hypertensive individuals . Patients were r and omized to amlodipine ( n=9048 ) or lisinopril ( n=9054 ) . The primary outcome was combined fatal coronary heart disease or nonfatal myocardial infa rct ion , analyzed by intention-to-treat . Secondary outcomes included all-cause mortality , stroke , combined cardiovascular disease ( CVD ) , end-stage renal disease ( ESRD ) , cancer , and gastrointestinal bleeding . Mean follow-up was 4.9 years .  Blood pressure control was similar in nonblacks , but not in blacks . No significant differences were found between treatment groups for the primary outcome , all-cause mortality , ESRD , or cancer . Stroke rates were higher on lisinopril in blacks ( RR=1.51 , 95 % CI 1.22 to 1.86 ) but not in nonblacks ( RR=1.07 , 95 % CI 0.89 to 1.28 ) , and in women ( RR=1.45 , 95 % CI 1.17 to 1.79 ) , but not in men ( RR=1.10 , 95 % CI 0.92 to 1.31 ) . Rates of combined CVD were higher ( RR=1.06 , 95 % CI 1.00 to 1.12 ) because of higher rates for strokes , peripheral arterial disease , and angina , which were partly offset by lower rates for heart failure ( RR=0.87 , 95 % CI 0.78 to 0.96 ) on lisinopril compared with amlodipine .  Gastrointestinal bleeds and angioedema were higher on lisinopril . Patients with and without baseline coronary heart disease showed similar outcome patterns . We conclude that in hypertensive patients , the risks for coronary events are similar , but for stroke , combined CVD , gastrointestinal bleeding , and angioedema are higher and for heart failure are lower for lisinopril-based compared with amlodipine-based therapy . Some , but not all , of these differences may be explained by less effective blood pressure control in the lisinopril arm Background Hypertension is strongly associated with cognitive decline and a promising target for dementia prevention . Our aim was to investigate the association between different antihypertensive treatments and cognitive performance in elderly hypertensive patients presenting with subjective memory complaints . Patients and methods Three hundred and seventy-eight elderly hypertensive patients more than 60 years ( mean age 70.4 ± 6.3 years ) treated with at least one antihypertensive agent and presenting with subjective memory complaints but without dementia were prospect ively recruited and underwent a combination of neuropsychological tests , brain magnetic resonance imaging with semiquantification of white matter hyperintensities , carotid echotracking , brachial endothelial function , and ambulatory blood pressure assessment s. Results None of the three composite scores ( memory score , verbal fluency , and visual memory capacity ) was found associated with blood pressure levels . On the other h and , age-adjusted and sex-adjusted analyses showed a significant and positive association between memory score and use of calcium channel blockers ( CCBs ) ( users : + 0.14 ± 0.09 versus nonusers : −0.12 ± 0.06 ; P = 0.016 ) . Multivariate analyses also revealed that CCB use was significantly associated with a better memory score , independently of age , male sex , white matter hyperintensities , and carotid wall cross-sectional area , all of which were associated with worse memory scores . Conclusion In elderly hypertensive treated patients with subjective memory complaints  , CCB use was associated with better memory performance independently of blood pressure level and macrovascular and microvascular alterations , suggesting a specific neuroprotective effect of this pharmacological class . Interventional controlled trials are required to confirm the specific protective effect of CCBs on cognitive decline Dihydropyridine and nondihydropyridine calcium channel blockers ( CCB ) differ in pharmacologic characteristics . Few clinical studies distinguish effects of CCB as monotherapy . We conducted a comprehensive comparison of two CCB on patients with moderate to severe hypertension . Thirty patients with pretreatment diastolic blood pressures > or = 100 mm Hg were r and omly assigned to either nifedipine-GITS or verapamil-SR . Dose titration achieved a diastolic blood pressure of < or = 95 mm Hg or a decrease of > or = 15 mm Hg over 4 weeks . Clinic blood pressure ( BP ) , 24-h ambulatory BP , exercise BP , left ventricular mass , systolic and diastolic function by echocardiography , and coronary flow reserve by split-dose thallium-201 imaging  with adenosine were assessed at baseline , end of titration , 3 months and 6 months of treatment . Plasma renin activity , atrial natriuretic peptide , norepinephrine , and epinephrine were assayed . Both drugs caused similar reductions in clinic and 24-h ambulatory BP and similar reductions in left ventricular mass index . Compared to nifedipine-GITS , verapamil-SR produced a significantly lower resting and peak exercise heart rate .  Nifedipine-GITS elicited a lower peak exercise systolic BP . At end titration nifedipine-GITS produced lower plasma atrial natriuretic peptide levels , no longer apparent by 6 months . Plasma norepinephrine was lower with verapamil-SR , also at end titration and at 3 months , but not at 6 months . Plasma epinephrine and plasma renin activity were unchanged by either drug . There was no difference for systolic or diastolic left ventricular function or coronary flow reserve between the two treatments . Once daily nifedipine-GITS and verapamil-SR are equally effective for reduction of arterial pressure in moderate to severe hypertension . Differences in their hemodynamic profiles and neurohormonal responses are consistent with pre clinical pharmacologic characteristics . The clinical implication s of their similarities and differences remain to be fully evaluated in outcome studies OBJECTIVE To assess the association between  first myocardial infa rct ion and the use of antihypertensive agents .  DESIGN AND SETTING We conducted a population -based case-control study among enrollees of the Group Health Cooperative of Puget Sound ( GHC ) . PATIENTS AND METHODS Cases were hypertensive patients who sustained a first fatal or nonfatal myocardial infa rct ion from 1986 through 1993 among women and from 1989 through 1993 among men . Controls were a stratified r and om sample of hypertensive GHC enrollees , frequency matched to the cases on age , sex , and calendar year . All 623 cases and 2032 controls had pharmacologically treated hypertension . Data collection included a review of the ambulatory medical record a brief telephone interview of consenting survivors . Antihypertensive therapy was assessed using the GHC 's computerized pharmacy data base . RESULTS The first analysis included only the 335 cases and 1395 controls initially free of cardiovascular disease . Compared with users of diuretics alone , the adjusted risk ratio of myocardial infa rct ion was increased by about 60 % among users of calcium channel blockers with or without diuretic ( risk ratio = 1.62 % ; 95 % confidence interval [ Cl ] , 1.11 to 2.34 ; P = .01 ) . The second analysis was restricted to 384 cases and 1108 controls who were taking either a calcium channel blocker or a beta-blocker .  Among these subjects , the use of calcium channel blockers compared with beta-blockers was associated with about a 60 % increase in the adjusted risk of myocardial infa rct ion ( risk ratio = 1.57 ; 95 % Cl , 1.21 to 2.04 ; P < .001 ) . While high doses of beta-blockers were associated with a decreased risk of myocardial infa rct ion ( trend P = .04 ) , high doses of calcium channel blockers were associated with an increased risk ( trend P < .01 ) . CONCLUSIONS In this study of hypertensive patients , the use of short-acting calcium channel blockers , especially in high doses , was associated with an increased risk of myocardial infa rct ion . Ongoing large-scale clinical trials will assess the effect of various antihypertensive therapies , including calcium channel blockers , on several important cardiovascular end points . Until these results are available , the findings of this study support the current guidelines from the Joint National Committee on the Detection , Evaluation and Treatment of High Blood Pressure that recommend diuretics and beta-blockers as first-line agents unless contraindicated , unacceptable , or not tolerated A multicenter , r and omized , controlled , double-blind U.S. trial is comparing the combined effects of diet treatment and 1 of 5 active drug regimens with diet treatment alone , for the long-term management of middle-aged adults with " mild " hypertension . Factors stimulating this trial are data documenting the high prevalence of mild hypertension in the adult population ; mild hypertension 's responsibility for a high proportion of morbidity and mortality attributable to hypertension overall ; data from long-term hypertension intervention trials showing reduced morbidity and mortality of people with mild hypertension with use of either diuretics or beta blockers as step-1 therapy , and other trials that failed to demonstrate beneficial impact on morbidity and mortality , possibly due to residual questions concerning aspects of benefit to risk ratios with these medications ; recent data from trials showing long-term control of mild hypertension and other risk factors by nutritional means ; lack of data from long-term trials on benefit to risk ratios with newer drugs such as selective alpha 1 inhibitors , angiotensin converting enzyme inhibitors and calcium channel blockers ; paucity of data from trials on long-term combined effects of diet and drug therapy , and of diet alone , for people with mild hypertension . During the next few years , phase 1 of the trial will study 6 groups of drugs . The step-1 drugs are angiotensin converting enzyme inhibitor ( enalapril ) , alpha 1 inhibitor ( doxazosin ) , beta blocker ( acebutolol ) , calcium channel blocker ( amlodipine ) , diuretic ( chlorthalidone ) and placebo . All participants are to receive vigorous sustained nutritional counseling to reduce obesity , moderate sodium intake and avoid heavy use of alcohol . Key endpoints for phase 1 of the study are the need for additional medication to control mild hypertension , side effects ( i.e. , clinical and biochemical ) and consequent need to discontinue drug and quality of life . Phase-1 data are to be used to complete the phase-2 design , with the ultimate aim to assess effects on morbidity and mortality BACKGROUND Recent reports suggest that calcium-channel blockers may be harmful in patients with diabetes and hypertension . We previously reported that antihypertensive treatment with the calcium-channel blocker nitrendipine reduced the risk of cardiovascular events . In this post hoc analysis , we compared the outcome of treatment with nitrendipine in diabetic and nondiabetic patients . METHODS After stratification according to center , sex , and presence or absence of previous cardiovascular complications , 4695 patients ( age , > or = 60 years ) with systolic blood pressure of 160 to 219 mm Hg and diastolic pressure below 95 mm Hg were r and omly assigned to receive active treatment or placebo . Active treatment consisted of nitrendipine ( 10 to 40 mg per day ) with the possible addition or substitution of enalapril ( 5 to 20 mg per day ) or hydrochlorothiazide ( 12.5 to 25 mg per day ) or both , titrated to reduce the systolic blood pressure by at least 20 mm Hg and to less than 150 mm Hg . In the control group , matching placebo tablets were administered similarly . RESULTS At r and omization , 492 patients ( 10.5 percent ) had diabetes . After a median follow-up of two years , the systolic and diastolic blood pressures in the placebo and active-treatment groups differed by 8.6 and 3.9 mm Hg , respectively , among the diabetic patients . Among the 4203 patients without diabetes , systolic and diastolic pressures differed by 10.3 and 4.5 mm Hg , respectively , in the two groups . After adjustment for possible confounders , active treatment was found to have reduced overall mortality by 55 percent ( from 45.1 deaths per 1000 patients to 26.4 deaths per 1000 patients ) , mortality from cardiovascular disease by 76 percent , all cardiovascular events combined by 69 percent , fatal and nonfatal strokes by 73 percent , and all cardiac events combined by 63 percent in the group of patients with diabetes . Among the nondiabetic patients , active treatment decreased all cardiovascular events combined by 26 percent and fatal and nonfatal strokes by 38 percent . In the group of patients receiving active treatment , reductions in overall mortality , mortality from cardiovascular disease , and all cardiovascular events were significantly larger among the diabetic patients than among the nondiabetic patients ( P=0.04 , P=0.02 , and P=0.01 , respectively ) . CONCLUSIONS Nitrendipine-based antihypertensive therapy is particularly beneficial in older patients with diabetes and isolated systolic hypertension . Thus , our findings do not support the hypothesis that the use of long-acting calcium-channel blockers may be harmful in diabetic patients
In a pooled analysis of data of 31 RCTs measuring the effect of CCBs  on stroke  , CCBs  reduced stroke more than placebo and β-adrenergic blockers , but were not different than ACEIs and diuretics .
BACKGROUND Hypertension is a major risk factor for the development of stroke .
It is well known that lowering blood pressure decreases the risk of stroke in people with moderate to severe hypertension .
However , the specific effects of calcium channel blockers ( CCBs ) against stroke in patients with hypertension as compared to no treatment and other antihypertensive drug classes are not known .