Treatment of hypertension with dihydropyridine calcium antagonists and aspirin. Comparison of two calcium blockers on hemodynamics, left ventricular mass, and coronary vasodilatory in advanced hypertension. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). Effects of calcium-channel blockade in older patients with diabetes and systolic hypertension. Systolic Hypertension in Europe Trial Investigators. Treatment of mild-to-moderate hypertension with calcium channel blockers: a multicentre comparison of once-daily nifedipine GITS with once-daily amlodipine The effects of increasing calcium channel blocker dose vs. adding a diuretic to treatment regimens for patients with uncontrolled hypertension ACE inhibitors, beta-blockers, calcium blockers, and diuretics for the control of systolic hypertension. Randomised trial of effects of calcium antagonists compared with diuretics and β-blockers on cardiovascular morbidity and mortality in hypertension: the Nordic Diltiazem (NORDIL) study Effect of different antihypertensive drug classes on central aortic pressure. Cardiovascular events in elderly patients with isolated systolic hypertension. A subgroup analysis of treatment strategies in STOP‐Hypertension‐2 Dementia risk with antihypertensive use and blood pressure variability Combinations of olmesartan and a calcium channel blocker or a diuretic in elderly hypertensive patients: a randomized, controlled trial1 Calcium channel blockers and cardiac mortality in the treatment of hypertension: a report from the Department of Health Hypertension Care Computing Project (DHCCP) Combination Therapy of Calcium Channel Blocker and Angiotensin II Receptor Blocker Reduces Augmentation Index in Hypertensive Patients Randomized double-blind comparison of a calcium antagonist and a diuretic in elderly hypertensives. National Intervention Cooperative Study in Elderly Hypertensives Study Group. 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 Calcium Antagonist Isradipine in the Therapy of Hypertension
The effects of dihydropyridine calcium antagonists on blood pressure and platelets , and the effects of aspirin on the circadian antihypertensive efficacy of dihydropyridines and on the 24-h platelet-activity profile , were the focus of a double-blind study . Patients with essential hypertension were treated for 8 weeks with either isradipine focus of double-blind study . Patients with essential hypertension were treated for 8 weeks with either isradipine ( 2.5 mg/day ) or nitrendipine ( 10 mg/day ) . Aspirin ( 100 mg/day ) was added to both treatment groups for a further 8 weeks . Measurements were taken after 4 weeks of placebo , after 8 weeks of dihydropyridine treatment , and after 8 weeks of treatment combined with aspirin .  Plasma levels of beta-thromboglobulin ( beta-TG ) and platelet aggregation induced by serotonin were measured six times during 24 h. Both dihydropyridines significantly lowered systolic and diastolic blood pressure . The addition of aspirin to dihydropyridine treatment had no significant effects on systolic or diastolic blood pressure .  Dihydropyridine treatment lowered the increased 24-h plasma beta-TG profile and inhibited platelet aggregability .  Aspirin added to nitrendipine led to a further significant decrease in beta-TG levels whereas its addition to isradipine was accompanied by a partial increase in plasma beta-TG . It is concluded that increases in platelet activity in hypertensive patients can be prevented with either isradipine alone or nitrendipine plus aspirin . Aspirin in a daily dose of 100 mg does not affect the antihypertensive efficacy of calcium antagonists 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 Hypertension is the most common condition seen in primary care and leads to myocardial infa rct ion , stroke , renal failure , and death if not detected early and treated appropriately . Patients want to be assured that blood pressure ( BP ) treatment will reduce their disease burden , while clinicians want guidance on hypertension management using the best scientific evidence . This report takes a rigorous , evidence -based approach to recommend treatment thresholds , goals , and medications in the management of hypertension in adults . Evidence was drawn from r and omized controlled trials , which represent the gold st and ard for determining efficacy and effectiveness . Evidence quality and recommendations were grade d based on their effect on important outcomes . There is strong evidence to support treating hypertensive persons aged 60 years or older to a  BP goal  of less than 150/90 mm Hg and hypertensive persons 30 through 59 years of age to a diastolic goal of less than 90 mm Hg ; however , there is insufficient evidence in hypertensive persons younger than 60 years for a systolic goal , or in those younger than 30 years for a diastolic goal , so the panel recommends a BP of less than 140/90 mm Hg for those groups based on expert opinion . The same thresholds and goals are recommended for hypertensive adults with diabetes or nondiabetic chronic kidney disease ( CKD ) as for the general hypertensive population younger than 60 years . There is moderate evidence to support initiating drug treatment with an angiotensin-converting enzyme inhibitor , angiotensin receptor blocker , calcium channel blocker , or thiazide-type diuretic in the nonblack hypertensive population , including those with diabetes . In the black hypertensive population , including those with diabetes , a calcium channel blocker or thiazide-type diuretic is recommended as initial therapy . There is moderate evidence to support initial or add-on antihypertensive therapy with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker in persons with CKD to improve kidney outcomes . Although this guideline provides evidence -based recommendations for the management of high BP and should meet the clinical needs of most patients , these recommendations are not a substitute for clinical judgment , and decisions about care must carefully consider and incorporate the clinical characteristics and circumstances of each individual patient 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 SUMMARY Background : Hypertension is one of the most important causes of cardiovascular disease , and treatment of hypertension leads to a significant reduction in cardiovascular mortality and morbidity . Although calcium channel blockers are regarded as an important part of the therapeutic armamentarium against cardiovascular diseases , and are among the most frequently prescribed antihypertensive medications , concern has been aroused about these drugs , particularly the short-acting dihydropyridine derivatives . However , the value of nifedipine GITS ( Adalat-Crono * ) , the long-acting dihydropyridine , is in need of being re-established . * Adalat-Crono is a registered tradename of Bayer AG , Leverkusen , Germany Objective : To compare the effectiveness , safety and tolerability of once-daily nifedipine and amlodipine treatment in patients with mild-to-moderate essential hypertension . Design : R and omised multicentre trial with an open comparison of treatments for 12 weeks , with a preceding placebo run-in period of 2 weeks ( patients on beta-blockers at the time of enrolment entered a m and atory 2-week wash-out period before being allowed in the placebo run-in period ; this wash-out period was one week for patients using any antihypertensive medication other than beta-blockers ) . Setting : Nine centres ( all university hospitals ) in Turkey . Patients : 155 patients with essential hypertension ( diastolicblood pressure 95 - 109 mmHg ) . Interventions : Initial treatment ( step 1 ) consisted of 30 mg nifedipine GITS ( n = 76 ; ( Adalat-Crono tablets ) , or 5 mg amlodipine ( n = 79 ; Norvasc * 5-mg tablets ) , either administered once daily , as a morning dose , or if the blood pressure was not below 140/90 mmHg , or the reduction in diastolic blood pressure was lower than 10 mmHg after a treatment period of 6 weeks , the dose was increased ( Step 2 ) to 60 mg once daily in the nifedipine group , or 10 mg once daily in the amlodipine group . Main efficacy parameter : Diastolic blood pressure at trough after 12 weeks of active compound therapy adjusted to baseline . Results : After 12 weeks of treatment , the mean diastolic blood pressure was 83.1 and 81.9 mmHg , in the nifedipine and amlodipine groups , respectively ( p = 0.436 ) . The mean decrease in systolic blood pressure ( 28.5 ± 11.9 and 28.2 ± 11.2 mmHg in the nifedipine and amlodipine groups , respectively ) and the mean decrease in diastolic blood pressure ( 16.4 ± 7.0 and 17.5 ± 6.9 mmHg in the nifedipine and amlodipine groups , respectively ) , as well as the responder rates ( 88.1 % and 92.1 % , in the nifedipine and amlodipine groups , respectively ) were comparable at the end of the study . No significant differences between groups were detected in the efficacy parameters assessed in this study . Both drugs were well tolerated . The overall incidence of adverse events was 7.9 % in the nifedipine group and 10.1 % in the amlodipine group . However , more patients discontinued treatment prematurely in the amlodipine group ( 13 patients ; 19.7 % ) , than in the nifedipine group ( four patients ; 5.6 % ) . Conclusions : The results of this study demonstrated that once-daily nifedipine in GITS formulation and amlodipine are comparably safe and effective treatment options in patients with mild-to-moderate essential hypertensi on 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 objective of this study was to determine which of the common groups of antihypertensive drugs is most effective at lowering systolic blood pressure ( SBP ) in elderly patients with previously untreated hypertension and the percentage of patients controlled with single or sequential monotherapy . Subjects were recruited from patients attending other outpatient clinics and entered into the study if their SBP was more than 150 mm Hg after three visits . Patients were given a low and high dose of each of the main classes of drugs or placebo for 1 month each . The study was a balanced , r and omized crossover design with five periods : placebo ; angiotensin converting enzyme inhibitors ; beta-blocking drugs ; calcium-blocking drugs ; and thiazide diuretics .  Blood pressure ( BP ) was measured 24 to 26 h after the previous dose . A question naire for side effects was administered at each visit . Seventy-four patients entered the study . beta-Blockers could not be used in 15 patients because of asthma or bronchospasm and these had two placebo periods . There were 9 of 66 patients on P , 9 of 46 on beta-blockers , 4 of 65 on calcium-blocking drugs , 4 of 65 on diuretic , and 1 of 62 patients on ACE inhibitors who did not progress to the higher dose because of side effects . Decreases in SBP compared to r and omized placebo were calcium-blocking drugs 15 mm Hg = diuretic 13 mm Hg > ACE inhibitors 8 mm Hg = beta-blockers 5 mm Hg . Blood pressure decrease correlated with placebo BP ( P < .0005 , r = 0.53 to 0.70 ) . When corrected for placebo , target SBP ( < 140 mm Hg ) was reached in between 6 % to 15 % of patients on monotherapy . Sequential monotherapy achieved target in 29 % . Angiotensin converting enzyme inhibitors , calcium-blocking drugs , and diuretics had no more side effects than placebo . Patients on beta-blockers had more side effects and the well-being score was reduced . Diuretics and calcium-blocking drugs are more effective in elderly patients at lowering SBP pressure . beta-Blockers were relatively ineffective , were frequently contraindicated , and had more side effects . Monotherapy achieved control in only a small number of patients . In elderly people with essential hypertension , therapy should be instituted with diuretics or calcium-blocking drugs , but combination therapy will usually be required to achieve goal BACKGROUND Calcium antagonists are a first-line treatment for hypertension . The effectiveness of diltiazem , a non-dihydropyridine calcium antagonist , in reducing cardiovascular morbidity or mortality is unclear . We compared the effects of diltiazem with that of diuretics , beta-blockers , or both on cardiovascular morbidity and mortality  in hypertensive patients . METHODS In a prospect i ve , r and omised , open , blinded endpoint study , we enrolled 10,881 patients , aged 50 - 74 years , at health centres in Norway and Sweden , who had diastolic blood pressure of 100 mm Hg or more . We r and omly assigned patients diltiazem , or diuretics , beta-blockers , or both . The combined primary endpoint was fatal and non-fatal stroke , myocardial infa rct ion , and other cardiovascular death . Analysis was done by intention to treat . FINDINGS Systolic and diastolic blood pressure were lowered effectively in the diltiazem and diuretic and beta-blocker groups ( reduction 20.3/18.7 vs 23.3/18.7 mm Hg ; difference in systolic reduction p<0.001 ) . A primary endpoint occurred in 403 patients in the diltiazem group and in 400 in the diuretic and beta-blocker group ( 16.6 vs 16.2 events per 1000 patient-years ; relative risk 1.00 [ 95 % CI 0.87 - 1.15 ] , p=0.97 ) . Fatal and non-fatal stroke occurred in 159 patients in the diltiazem group and in 196 in the diuretic and beta-blocker group ( 6.4 vs 7.9 events per 1000 patient-years ; 0.80 [ 0.65 - 0.99 ] , p=0.04 ) and fatal and non-fatal myocardial infa rct ion in 183 and 157 patients ( 7.4 vs 6.3 events per 1000 patient-years ; 1.16 [ 0.94 - 1.44 ] , p=0.17 ) . INTERPRETATION Diltiazem was as effective as treatment based on diuretics , beta-blockers , or both in preventing the combined primary endpoint of all stroke , myocardial infa rct ion , and other cardiovascular death 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 perform a subgroup analysis on those patients in STOP‐Hypertension‐2 who had isolated systolic hypertension . Design and methods : The STOP‐Hypertension‐2 study evaluated cardiovascular mortality and morbidity in elderly hypertensives comparing treatment with conventional drugs ( diuretics , beta‐blockers ) with that of newer ones [ angiotensin‐converting enzyme ( ACE ) inhibitors , calcium antagonists ] . In all , 6614 elderly patients with hypertension ( mean age 76.0 years , range 70–84 years at baseline ) were included in STOP‐Hypertension‐2 . In the present subgroup analysis of STOP‐Hypertension‐2 , isolated systolic hypertension was defined as systolic blood pressure at least 160 mmHg and diastolic blood pressure below 95 mmHg , in accordance with the Syst‐Eur and Syst‐China study criteria . In total , 2280 patients in STOP‐Hypertension‐2 met these criteria . In the study , patients were r and omized to one of three treatment groups : “ conventional ” antihypertensive therapy with beta‐blockers or diuretics ( atenolol 50 mg , metoprolol 100 mg , pindolol 5 mg , or fixed‐ratio hydrochlorothiazide 25 mg plus amiloride 2.5 mg daily ) ; ACE inhibitors ( enalapril 10 mg or lisinopril 10 mg daily ) ; or calcium antagonists ( felodipine 2.5 mg or isradipine 2.5 mg daily ) . Analysis was by intention to treat . Results : The blood pressure lowering effect in patients with systolic hypertension was similar with all three therapeutic regimens : 35/13 mmHg in the conventional group ( n = 717 ) , 34/12 mmHg in the ACE inhibitor group ( n = 724 ) , and 35/13 mmHg in the calcium antagonist group ( n = 708 ) . Prevention of cardiovascular mortality , the primary endpoint of the study , did not differ between the three treatment groups . All stroke events , i.e. fatal and non‐fatal stroke together , were significantly reduced by 25 % in the newer‐drugs group compared with the conventional group ( 95 % CI 0.58–0.97 ; p = 0.027 ) . This difference was attributable to reduction of non‐fatal stroke while fatal stroke events did not differ between groups . New cases of atrial fibrillation were significantly increased by 43 % ( 95 % CI 1.02–1.99 ; p = 0.037 ) on “ newer ” drugs compared with “ conventional ” therapy , mainly attributable to the calcium antagonists . There were no significant differences between the three treatment groups with respect to the risks of myocardial infa rct ion , sudden death or congestive heart failure . Conclusions : The analysis demonstrated that “ newer ” therapy ( ACE inhibitors/calcium antagonists ) was significantly better ( 25 % ) than “ conventional ” ( diuretics/beta‐blockers ) in preventing all stroke in elderly patients with isolated systolic hypertension Objective : To determine the association between discrete antihypertensive drug classes and incident dementia controlling for blood pressure variability ( BPV ) in the preceding 4 years . Methods : A total of 6,537 participants ( mean age 79 years , 62 % women ) in a prospect i ve population -based cohort were followed up for incident dementia . A 4-year time lag period was created to classify drug exposure and measure blood pressure . BPV ( percent coefficient of variation [ CV ] ) was regressed against 9 antihypertensive drug classes ( BPVreg ) . Cox regression models were employed to determine hazard ratios ( HRs ) for incident dementia thereafter according to drug class , adjusted for mean blood pressure , covariates , and BPV or BPVreg . Results : Over a median 8.4 years follow-up ( interquartile range 6.7–9.0 ) , lower dementia risk was associated with nondihydropyridine calcium channel blocker ( HR 0.56 ; 95 % confidence interval [ CI ] 0.31–1.00 , p = 0.05 ) and loop diuretics ( HR 0.45 ; 95 % CI 0.22–0.93 , p = 0.03 ) after adjusting for CV-BPV . Similar findings were obtained in analyses restricted to antihypertensive drug users for nondihydropyridine calcium channel blocker ( HR 0.52 ; 95 % CI 0.28–0.95 , p = 0.03 ) and loop diuretics ( HR 0.40 ; 95 % CI 0.19–0.83 , p = 0.01 ) . All systolic BPV × antihypertensive drug interaction terms were not different from p < 0.05 . Conclusions : Nondihydropyridine calcium channel blocker and loop diuretics were associated with a reduced dementia risk independent of CV-BPV in the preceding 4 years . Systolic BPV was not the primary mechanism through which antihypertensive drug classes lower dementia risk 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 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 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 Although diuretics are recommended for the treatment of hypertension , decreased diuretic use and increased calcium antagonist use necessitate a comparison of the efficacy of these drugs in preventing cardiovascular events .  Patients > /=60 years of age with systolic blood pressure of 160 to 220 mm Hg and diastolic blood pressure < 115 mm Hg were enrolled . Patients were r and omly assigned to 20 mg of sustained-release nicardipine hydrochloride twice daily or 2 mg of trichlormethiazide once daily by the double-dummy method and followed up for 5 years . A total of 414 patients were analyzed : 204 in the nicardipine group and 210 in the diuretic group .  Blood pressure  at entry was 172/94 mm Hg and 173/93 mm Hg , respectively , and decreased to 147/81 mm Hg and 147/79 mm Hg , respectively . Cardiovascular morbidity rates per 1000 persons per year were similar in the nicardipine and diuretic groups ( 27.8 and 26.8 , respectively ; P=0.923 ) . The sex- and age-adjusted risk ratio for the nicardipine group was 0.973 ( 95 % confidence interval , 0.514 to 1.839 , P=0.932 ) . The calcium antagonist and diuretic groups had a similarly decreased rate of cardiovascular events 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 Summary The calcium antagonists of the dihydropyridine group , isradipine and nifedipine , were compared in 64 patients with mild to moderate hypertension ( diastolic blood pressure 95 to 110 mm Hg ) . A 2-week placebo run-in phase was followed by a double-blind crossover trial comprising two 3-week treatment periods with either calcium antagonist . The ( fixed ) dosages were isradipine 2.5 mg twice daily and nifedipine retard 20 mg twice daily . Blood pressure ( systolic/diastolic ) at baseline was 155/101 mm Hg and decreased significantly by 14%/15 % on isradipine and by 11%/12 % on nifedipine ( difference between treatments not significant ) . The drugs differed significantly with regard to incidence of adverse effects ( mostly flushing and headache ) ; the total rates were 16 % on isradipine and 36 % on nifedipine . At the end of the trial , patients were asked which drug or treatment phase they preferred . Isradipine was preferred by 50 % of patients ; only 20 % preferred nifedipine . Thus , it is concluded that isradipine , administered in an equally effective antihypertensive dosage regimen is superior to nifedipine with regard to the incidence of adverse effects , result ing in greater patient satisfaction with treatment
Once-daily dihydropyridine calcium channel blockers appeared to lower blood pressure by a relatively constant amount throughout the 24-hour dosing interval .
Six dihydropyridine calcium channel blockers studied in this review lowered blood pressure by a relatively similar amount each hour over the course of 24 hours .
BACKGROUND Calcium channel blockers are a heterogeneous class of drugs , including dihydropyridine and non-dihydropyridine subgroups , commonly used in the treatment of hypertension .
A systematic review of the 24-hour time course of the blood pressure-lowering effect has not been published .
OBJECTIVES To assess how much variation there is in hourly systolic and diastolic blood pressure lowering by dihydropyridine calcium channel blockers over a 24-hour period in people with hypertension aged 18 years or over , with baseline systolic blood pressure of at least 140 mmHg or diastolic blood pressure of at least 90 mmHg , or both .