Calcium channel blockers and cardiac mortality in the treatment of hypertension: a report from the Department of Health Hypertension Care Computing Project (DHCCP) 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 Calcium-channel blockers and cognitive function in elderly people: results from the Canadian Study of Health and Aging. Effect of irbesartan monotherapy compared with ACE inhibitors and calcium‐channel blockers on patient compliance in essential hypertension patients: A multicenter, open‐labeled, three‐armed study Renoprotective Effect of Calcium Channel Blockers in Combination with an Angiotensin Receptor Blocker in Elderly Patients with Hypertension. A Randomized Crossover Trial Between Benidipine and Amlodipine The risk of myocardial infarction associated with antihypertensive drug therapies. Use of calcium channel blockers is associated with better cognitive performance in older hypertensive patients with subjective memory complaints Effect of different antihypertensive drug classes on central aortic pressure. A computerized intervention to decrease the use of calcium channel blockers in hypertension Angiotensin-converting enzyme inhibitors, calcium channel blockers, and breast cancer. Comparison of two calcium blockers on hemodynamics, left ventricular mass, and coronary vasodilatory in advanced hypertension. Combination of antihypertensive therapy in the elderly, multicenter investigation (CAMUI) trial. Rationale, design and patient baseline characteristics of OlmeSartan and calcium antagonists randomized (OSCAR) study: a study comparing the incidence of cardiovascular events between high-dose angiotensin II receptor blocker (ARB) monotherapy and combination therapy of ARB with calcium channel bloc Calcium channel blockers versus other antihypertensive therapies on progression of NIDDM associated nephropathy. Combinations of olmesartan and a calcium channel blocker or a diuretic in elderly hypertensive patients: a randomized, controlled trial1 Renoprotective Effect and Cost-Effectiveness of Using Benidipine, a Calcium Channel Blocker, to Lower the Dose of Angiotensin Receptor Blocker in Hypertensive Patients with Albumiuria Combination Therapy of Calcium Channel Blocker and Angiotensin II Receptor Blocker Reduces Augmentation Index in Hypertensive Patients
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 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 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 Objectives . This multicenter , three‐armed , open‐labeled study investigated patient compliance of patients receiving irbesartan , angiotensin‐converting enzyme ( ACE ) inhibitors or calcium‐channel blockers ( CCB ) for essential hypertension for a 6‐month period . Patients were either newly diagnosed or switched from existing antihypertensive medication due to lack of efficacy or side‐effects . Methods . Patients were started monotherapy with irbesartan ( n = 377 ) , ACE inhibitors ( n = 298 ) or CCB ( n = 308 ) and were reevaluated on 1st , 3rd , and 6th months of the treatment . The primary endpoint was patient compliance , assessed by proportion of patients who had taken their study medication every day . Efficacy was recorded as mean reductions in blood pressure and the proportion of patients whose blood pressure normalized . Tolerability was assessed by reported adverse events . Results . Significantly more patients receiving irbesartan had complied with study medication after 3 and 6 months of treatment than ACE inhibitors or CCB . Significantly fewer patients receiving irbesartan needed to change their antihypertensive medication . All three study treatments exhibited similar efficacy profiles , but irbesartan had significantly less adverse events . Conclusions . This study demonstrated that patient compliance to irbesartan was significantly superior to other study treatments . Irbesartan is therefore a suitable first‐line therapy for essential hypertension in everyday clinical practice Anti-hypertensive medication with an angiotensin II receptor blocker ( ARB ) is effective in slowing the progression of chronic kidney disease . The present study was design ed to investigate whether calcium channel blockers ( CCBs ) in combination with an ARB differentially affect kidney function . Elderly hypertensive patients with chronic kidney disease ( n = 17 , 72 ± 6 years old ) were instructed to self-measure blood pressure . They were r and omly assigned to receive either benidipine ( 4–8 mg/day ) or amlodipine ( 5–10 mg/day ) combined with olmesartan ( 10 mg/day ) . After 3 months , CCBs were switched in each patient and the same protocol was applied for another 3 months . At baseline , significant correlation was obtained between urine albumin ( 22.8 ± 16.7 ( median ± median absolute deviation ) mg/g creatinine ) and self-measured blood pressure ( 170 ± 23/87 ± 10 ( mean ± SD ) mmHg , r = 0.65 , p < 0.01 ) . Both regimens reduced blood pressure to a similar extent ( 139 ± 22/75 ± 11 mmHg and 133 ± 17/72 ± 10 mmHg , respectively ; both p < 0.001 ) , while urine albumin decreased only after combination therapy including benidipine ( 11.7 ± 6.1 mg/g creatinine , p < 0.05 ) . Benidipine , but not amlodipine , in combination with olmesartan , reduced urinary albumin excretion in elderly hypertensive patients with chronic kidney disease . The results suggest the importance of selecting medications used in combination with ARB in hypertensive patients with chronic kidney disease 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 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 Central aortic systolic blood pressure ( BP ) is an important determinant of cardiac workload and cardiac hypertrophy . The relationship of central aortic systolic BP and brachial BP varies depending on the stiffness of blood vessels . It is not certain whether the different drug classes affect the brachial and aortic systolic BP in a similar manner . In a double-blind crossover study , we measured the effects of the four major drug classes compared with placebo on central aortic pressure . Central aortic pressure and various indices were determined using the Sphygmo Cor apparatus . The study was undertaken in patients aged 65 to 85 years with systolic BP > 150 mm Hg at study entry . Results are reported for 32 patients who had satisfactory applanation tonometry in all five periods .  Calcium channel blockers and diuretics caused a greater fall in brachial artery systolic BP than angiotensin-converting enzyme ( ACE ) inhibitors or beta-blocking drugs . On placebo , central aorta augmentation pressure and index were 23 mm Hg and 33.3 % ; on ACE inhibitors the values were 18 mm Hg and 30 % ; on beta-blockers , 26 mm Hg and 38.5 % ; on calcium channel blockers , 16 mm Hg and 28 % ; and on diuretics , 17 mm Hg and 28.8 % . The augmentation pressure on beta-blocking drugs was greater than on the other three drug classes ( P < .05 ) , and augmentation pressures on ACE inhibitors , calcium channel blockers , and diuretics were less than on placebo ( P < .05 ) . The lowest central aortic pressures were achieved with calcium blocking drugs and diuretics . Therapy based on brachial artery recordings may thus overestimate the effect of beta-blocking drugs on central aortic systolic BP and underestimate the effectiveness of ACE inhibitors and calcium blocking drugs . The clinical importance of this discrepancy needs to be evaluated Objective To determine whether a computer-assisted reminder would alter prescribing habits for the treatment of hypertension in accordance with current clinical guidelines in a general internal medicine clinic . Design A r and omized trial . Setting The General Internal Medicine Clinic of the Veterans Affairs Puget Sound Health Care System , Seattle Division . Patients / Participants Clinic providers were r and omized to a control group ( n=35 ) or intervention group ( n=36 ) . We targeted the providers of patients being treated for hypertension with calcium channel blockers , a class of drug not recommended for initial therapy . InterventionAn automated computer query identified eligible patients and their providers . A guideline reminder was placed in the charts of patients of intervention providers ; the charts of patients of control providers received no reminder . Measurements and main results During the 5-month study period , 346 patients were seen by the 36 primary care providers ( staff physicians , nurse practitioners , residents , and fellows ) in the intervention group , and 373 patients were seen by the 35 providers in the control group . Intervention providers changed 39 patients ( 11.3 % ) to other medications during the study period , compared with 1 patient ( < 1.0 % ) of control providers ( p<.0001 ) . For patients whose therapy was unchanged , providers noted angina in 23.1 % , indications other than those for hypertension in 9.5 % , intolerable adverse effects with first-line therapy in 13.9 % , and inadequte control with first-line therapy in 13.9 % . Of those patients without provider-indicated contraindications , 23.6 % were switched from calcium channel blockers to first-line agents during the intervention period . Conclusions The use of a computerized , clinic-based intervention increased compliance with guidelines in the treatment of primary hypertension in general , and decreased the use of calcium channel blockers for the treatment of hypertension in particular 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 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 Angiotensin receptor blockers ( ARBs ) with calcium channel blockers ( CCBs ) or diuretics are a widely used combination therapy for hypertensive patients . The present study aim ed to determine which combination was better for elderly hypertension patients aged ≧ 65 years . We design ed a multicentre , r and omized , open-label , parallel comparison study . Hypertensive out patients aged ≧ 65 years who did not achieve the target blood pressure ( BP < 140/90 mmHg ) with usual dosages of ARBs  were r and omly assigned to switch treatment to losartan 50 mg/hydrochlorothiazide 12.5 mg or amlodipine 5 mg in addition to ARBs . The primary endpoint was a change in the systolic blood pressure ( SBP ) and diastolic blood pressure ( DBP ) after the 3-month treatment period , while secondary endpoints were changes in the BP , albuminuria , laboratory values , and cognitive function with the mini-mental state examination ( MMSE ) at baseline and after one year . The results from the CAMUI trial should provide new evidence for selecting optimal combination therapies for elderly hypertensive patients Higher doses of angiotensin II receptor blockers ( ARBs ) are expected to exert more protective effects against cardiovascular diseases . However , the significance of treatment of hypertension with high-dose ARB remains to be defined . The OlmeSartan and Calcium Antagonists R and omized ( OSCAR ) Study was design ed to determine whether high-dose ARB monotherapy is superior to the combination therapy of ARB plus calcium channel blocker ( CCB ) in the prevention of cardiovascular morbidity/mortality in Japanese elderly high-risk hypertensive patients . The OSCAR study is a multicenter , active-controlled , two-arm parallel group comparison , using the prospect i ve r and omized open-blinded end-point method . In the ‘ Step 1 ’ period , elderly hypertensive patients with diabetes or cardiovascular disease received monotherapy with ARB olmesartan medoxomil at a dose of 20 mg day−1 . If the target blood pressure control ( less than 140/90 mm Hg ) was not achieved by ARB monotherapy , the patients were r and omized to receive either ( 1 ) the increased dose of olmesartan at 40 mg day−1 ( high-dose ARB monotherapy ) or ( 2 ) the addition of a CCB ( amlodipine or azelnidipine ) to 20 mg day−1 olmesartan ( ARB plus CCB combination ) in the ‘ Step 2 ’ period . The follow-up duration will be 3 years . The primary end points will be the composite of fatal and non-fatal cardiovascular events , and death from any cause .  Recruitment for the OSCAR study ( around 1200 patients ) was completed by the end of May 2007 . The OSCAR study is the first large clinical trial comparing the efficacy of high-dose ARB monotherapy with that of an ARB plus CCB combination therapy in elderly high-risk hypertensive patients Treatment of hypertension with ACE inhibitors in diabetic patients reduces proteinuria and slows progression of nephropathy compared with agents that do not maintain declines in proteinuria . Calcium channel blockers ( CCBs ) have variable effects on proteinuria ; their long-term effects on progression of diabetic nephropathy are not known . The current study examines the hypothesis that CCBs that maintain reductions in proteinuria slow progression of nephropathy associated with non-insulin dependent diabetes mellitus ( NIDDM ) by a degree comparable to ACE inhibitors , given similar levels of blood pressure control . To test this hypothesis we r and omized 52 patients with NIDDM associated nephropathy and hypertension , mean age of 63 + /- 8 years , to either the ACE inhibitor , lisinopril ( N = 18 ) , nondihydropyridine CCBs ( NDCCBs ) , verapamil SR ( N = 8) or diltiazem SR ( N = 10 ) , or the beta blocker , atenolol ( N = 16 ) . Goal blood pressure was < or = 140/90 mm Hg . Patients were followed for a mean period of 63 + /- 7 months . The primary end point was change in creatinine clearance ( CCr ) slope in each group . There was no significant difference in mean arterial pressure reduction among the groups over the study period ( P = 0.14 ) . The mean rate of decline in CCr was greatest in the atenolol group ( -3.48 ml/min/year/1.73 m2 ; P < 0.0001 ) . There was no difference in the CCr slopes between lisinopril and NDCCBs groups ( P = 0.36 ) . Proteinuria was reduced to a similar extent in the lisinopril and NDCCBs groups ( P > 0.99 ) . Therefore , in persons with renal insufficiency secondary to NIDDM , similar levels of blood pressure control with either lisinopril or NDCCBs slowed progression of renal disease to a greater extent than atenolol . Moreover , this enhanced slowing of renal disease progression correlated with sustained and significant reductions in proteinuria , findings not observed in the atenolol group Objective : The aim of the present study was to compare the cardiovascular effects of olmesartan , an angiotensin II receptor blocker , combined with a calcium channel blocker ( CCB ) or a diuretic , in a prospect i ve , r and omized , open-label , blinded endpoint trial . Methods : Japanese hypertensive patients aged at least 65 to less than 85 years with SBP at least 140 mmHg and /or DBP at least 90 mmHg with antihypertensive treatment , or SBP at least 160 mmHg and /or DBP at least 100 mmHg without antihypertensive treatment were r and omized to receive olmesartan with either a dihydropyridine CCB or a low-dose diuretic . If SBP and /or DBP remained at least 140 and /or at least 90 mmHg , the other antihypertensive drug was added . The primary endpoint was a composite of fatal and nonfatal cardiovascular events . The median follow-up time was 3.3 years . Results : Blood pressure decreased similarly in both groups . The primary endpoint occurred in 116/2568 patients ( 4.5 % ) in the olmesartan plus CCB group and in 135/2573 patients ( 5.3 % ) in the olmesartan plus diuretic group [ hazard ratio 0.83 , 95 % confidence interval ( CI ) 0.65–1.07 , P = 0.16 ] . Rates of all-cause death and cardiovascular deaths were similar . Among patients aged at least 75 years , the incidence of stroke tended to be lower in the olmesartan plus CCB group than in the olmesartan plus diuretic group ( hazard ratio 0.63 , 95 % CI 0.38–1.02 , P = 0.059 , interaction P = 0.019 ) . Fewer patients in the olmesartan plus CCB group ( 8.2 % , 211/2568 ) than in the olmesartan plus diuretic group ( 9.8 % , 253/2573 ; P = 0.046 ) experienced serious adverse events . Conclusion : Despite no significant difference in cardiovascular events , the different safety profiles suggest that the combination of olmesartan and CCB may be preferable to that of olmesartan and diuretic In hypertensive patients with chronic renal disease ,  angiotensin receptor blockers ( ARBs ) are among the first-line drugs , and calcium channel blockers ( CCBs ) are recommended as a second line . We examined the effects of two therapeutic strategies using ARBs and benidipine , a CCB , on blood pressure ( BP ) , urinary albumin excretion ( UAE ) , and cost-effectiveness in hypertensive patients with albuminuria . Patients whose BP was 140/90 mmHg or higher despite treatment with low- or medium-dose ARBs were assigned r and omly to two groups . In Group A ( n=14 ) , the ARB dose was maximized and then benidipine was added until BP targets were reached ( < 130/85 mmHg ) . In Group B ( n=18 ) , benidipine was administered first and then the ARB dose was increased until BP targets were reached . The BP targets were achieved by ARB alone in 36 % of Group A patients and by the addition of benidipine in 83 % of Group B patients . Finally , BP decreased in each group , reaching the targets in 93 % of Group A patients and 94 % of Group B patients after a 4-month therapeutic period . UAE was decreased in both groups after a 4-month therapeutic period compared to the allocation period ( −33±6 % in Group A , −31±6 % in Group B ; p<0.001 , respectively ) . The monthly drug cost was higher ( 11,426±880 vs. 8,955±410 yen , p=0.012 ) and the cost-effectiveness of antihypertensive treatment was lower ( p=0.003 ) in Group A than in Group B. We conclude that the addition of benidipine to low- or medium-dose ARB is , in light of the renal protection and the cost-effectiveness of this approach , a useful therapeutic strategy for controlling BP in hypertensive patients with albuminuria Introduction : The optimal combination treatment for hypertension has not been established . We investigated the effect of a calcium channel blocker or a diuretic added to angiotensin II receptor blockers ( ARBs ) on the augmentation index ( AI ) , as a marker of arterial stiffness and wave reflection , in hypertensive patients . Methods : Thirty-seven patients treated with ARBs  were r and omly allocated to either of the 2 groups receiving an ARB plus azelnidipine ( AZ group ) or trichlormethiazide ( TCM group ) . Changes in brachial blood pressure ( BP ) , AI , high-sensitive C-reactive protein ( hsCRP ) , and serum asymmetric dimethylarginine , as an endogenous nitric oxide synthase inhibitor , were determined . Results : Systolic and diastolic blood pressure after 6 months were significantly reduced in both the groups similarly ; however , after adjustment for baseline covariates , the extent of the reduction in AI ( % ) in the AZ group was significantly greater than in the TCM group ( between-group difference was 3.2 ; 95%CI : 0.2–6.3 ; P = 0.03 ) . The reduction of high-sensitive C-reactive protein ( mg/L ) and serum asymmetric dimethylarginine ( & mgr;mol/L ) was significantly greater in the AZ group than in the TCM group ( between-group difference was 0.18 and 0.05 ; 95%CI : −0.01 to 0.36 and −0.01 to 0.11 ; P = 0.04 and 0.02 , respectively ) . Further , when patients were analyzed according to age younger than 60 years or older than 60 years , the reduction in AI in the AZ group aged older than 60 years was significantly greater than in the TCM group . Conclusion : The results suggest that azelnidipine has a more beneficial effect on vascular properties in combination therapy with ARB than trichlormethiazide
Diuretics are preferred first-line over CCBs to optimize reduction of cardiovascular events .
The review does not distinguish between CCBs , ACE inhibitors or ARBs , but does provide evidence supporting the use of CCBs over beta-blockers .
BACKGROUND Calcium channel blockers ( CCBs ) are a relatively new antihypertensive class .
The effect of first-line CCBs on the prevention of cardiovascular events , as compared with other antihypertensive drug classes , is unknown .
OBJECTIVES To determine whether CCBs used as first-line therapy for hypertension are different from other first-line drug classes in reducing the incidence of major adverse cardiovascular events .