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Calcium channel blocker compared with angiotensin receptor blocker for patients with hypertension: a meta-analysis of randomized controlled trials.

ABSTRACT: To explore the clinical effects of a calcium channel blocker compared with an angiotensin II receptor blocker in hypertensive patients, the authors collected data from randomized controlled trials. The pooled outcomes were all-cause mortality, stroke, myocardial infarction, and heart failure. Eight head-to-head trials enrolling 25,084 patients were included. There was no significant mortality difference in the two arms (relative risk, 0.99; 95% confidence interval, 0.91-1.07). However, calcium channel blockers were more effective in reducing stroke (relative risk, 0.87; 95% confidence interval, 0.76-0.99) and myocardial infarction incidence (relative risk, 0.86; 95% confidence interval, 0.76-0.98). There was no significant difference with heart failure incidence between the two arms but a lower trend in patients with angiotensin II receptor blockers was noted (relative risk, 1.4; 95% confidence interval, 0.99-1.98). The meta-analysis suggested that initially use of a calcium channel blocker might be superior to an angiotensin II receptor blocker for prevention of stroke and myocardial infarction.

SUBMITTER: Wu L

PROVIDER: S-EPMC8031805 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Biased safety reporting in blinded randomized clinical trials: meta-analysis of angiotensin receptor blocker trials.

Project description:BackgroundCough is listed as an adverse drug reaction (ADR) on the labels of angiotensin receptor blockers (ARB). However, a causal association with cough has also been reported for angiotensin converting enzyme inhibitors (ACEI), which have frequently been used as comparator drugs in the registration clinical trials of ARBs. This prompted us to examine the possible influence of using comparator drugs with well-known ADRs on the safety reporting of investigational drugs in blinded randomized clinical trials.Methods and findingsThe double-blinded, randomized clinical trials with comparator drugs were identified in the Japanese dossiers for the new drug applications of ARBs. The risk ratios (RR) of reporting cough and headache in ARB arms were calculated for each ARB by comparing trials using ACEIs and trials using non-ACEIs, were then combined with a meta-analysis. 23 trials with a total of 6643 patients were identified, consisting 6 trials using an ACEI comparator including 819 ARB patients and 17 trials using a non-ACEI comparator including 5824 ARB patients. The combined RR of cough reporting was significantly elevated (20.77; 95% confidence interval [CI], 7.47 to 57.76), indicating more frequent reporting of cough in clinical trials using an ACEI comparator. In contrast, the combined RR of headache, a negative control, was insignificant (1.45; 95% CI, 0.34 to 6.22).ConclusionThe use of comparators with well-known ADRs in blinded randomized trials produces potential bias in the reporting frequency of ADRs for investigational drugs. The selection of appropriate comparator drugs should be critical in unbiased safety assessment in double-blinded, randomized clinical trials and thus have relevance in reviewing the safety results from a regulatory point of view.

| S-EPMC3781030 | biostudies-literature

Medication compliance and clinical outcomes of fixed-dose combinations vs free combinations of an angiotensin II receptor blocker and a calcium channel blocker in hypertension treatment.

Project description:Using the National Health Insurance Research Database of Taiwan, the authors identified 1136 patients taking fixed-dose combination and 4544 patients taking free combinations of an angiotensin II receptor blocker and a dihydropyridine calcium channel blocker from January 2009 to December 2012. At a mean follow-up of 2.1 years, the fixed-dose combination was associated with improved medication adherence and persistence and better survival free from major adverse cardiac events and hospitalization for heart failure compared with the free combination regimens.

| S-EPMC8030826 | biostudies-literature

Dose Timing of an Angiotensin II Receptor Blocker/Calcium Channel Blocker Combination in Hypertensive Patients With Paroxysmal Atrial Fibrillation.

Project description:It has long been thought that there is a close association between hypertension and atrial fibrillation (AF). However, the efficacy of an angiotensin II receptor blocker for the prevention of organ damage in hypertensive individuals with AF is still controversial. The present study was a multicentered, prospective, randomized, open-label clinical trial investigating the differences in the effect of treatment with telmisartan/amlodipine combination tablets on blood pressure (BP) levels and BP variability between morning and bedtime administration in hypertensive patients with paroxysmal AF, using ambulatory BP monitoring (ABPM) and home BP. With this treatment, the patients' 24-hour BP, nighttime BP, preawake BP, and morning BP shown by ABPM were significantly reduced, and the antihypertensive effects were similar regardless of the timing of the drug administration. The standard deviation of day-by-day home systolic BP and the maximum home systolic BP were also significantly reduced, and these effects were similar regardless of the treatment timing. The N-terminal pro-brain natriuretic peptide level was significantly decreased only in the bedtime administration group. A larger study will demonstrate whether the bedtime administration of telmisartan/amlodipine combination tablets maximizes the risk-lowering effect against AF recurrence in paroxysmal AF hypertensive patients.

| S-EPMC8031835 | biostudies-literature

A meta-analysis of randomized controlled trials in pulmonary arterial hypertension.

Project description:AimsThere is no cure for pulmonary arterial hypertension, but current approved treatment options include prostanoids, endothelin-receptor antagonists, and phosphodiesterase type-5 inhibitors. The effect on survival of these compounds has not been appropriately assessed in individual trials because of small sample size and short duration. We performed a meta-analysis of all randomized controlled trials with drugs published in this condition.Methods and resultsTrials were searched in the Medline database from January 1990 to October 2008. The primary analysis included only studies with a placebo comparator arm, the sensitivity analysis also included studies comparing two active treatment arms. The main outcome measure was all-cause mortality. Twenty-one trials were included in the primary analysis (3140 patients) and two additional studies (59 patients) were included in the sensitivity analysis. Average duration of the trials was 14.3 weeks. All-cause mortality rate in the control group was 3.8%. Active treatments were associated with a reduction in mortality of 43% (RR 0.57; 95% CI 0.35-0.92; P = 0.023); the sensitivity analysis confirmed a reduction in mortality of 38% (RR 0.62; 95% CI 0.39-1.00; P = 0.048).ConclusionThe results of this meta-analysis suggest an improvement of survival in the patients treated with the targeted therapies approved for pulmonary arterial hypertension.

| S-EPMC2642921 | biostudies-literature

The effects of calcium channel blockers in the prevention of stroke in adults with hypertension: a meta-analysis of data from 273,543 participants in 31 randomized controlled trials.

Project description:BackgroundHypertension 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.Methods and findingsThis systematic review and meta-analysis of randomized controlled trials (RCTs) evaluated CCBs effect on stroke in patients with hypertension in studies of CCBs versus placebo, angiotensin-converting-enzyme inhibitors (ACEIs), ?-adrenergic blockers, and diuretics. The PUBMED, MEDLINE, EMBASE, OVID, CNKI, MEDCH, and WANFANG databases were searched for trials published in English or Chinese during the period January 1, 1996 to July 31, 2012. A total of 177 reports were collected, among them 31 RCTs with 273,543 participants (including 130,466 experimental subjects and 143,077 controls) met the inclusion criteria. In these trials a total of 9,550 stroke events (4,145 in experimental group and 5,405 in control group) were reported. CCBs significantly decreased the incidence of stroke compared with placebo (OR = 0.68, 95% CI 0.61-0.75, p<1×10(-5)), ?-adrenergic blockers combined with diuretics (OR = 0.89, 95% CI 0.83-0.95, p = 7×10(-5)) and ?-adrenergic blockers (OR = 0.79, 95% CI 0.72-0.87, p<1×10(-5)), statistically significant difference was not found between CCBs and ACEIs (OR = 0.92, 95% CI 0.8-1.02, p = 0.12) or diuretics (OR = 0.95, 95% CI 0.84-1.07, p = 0.39).ConclusionIn a pooled analysis of data of 31 RCTs measuring the effect of CCBs on stroke, CCBs reduced stroke more than placebo and ?-adrenergic blockers, but were not different than ACEIs and diuretics. More head to head RCTs are warranted.

| S-EPMC3590278 | biostudies-literature

Calcium channel blocker enhances beneficial effects of an angiotensin II AT1 receptor blocker against cerebrovascular-renal injury in type 2 diabetic mice.

Project description:Recent clinical trials have demonstrated that combination therapy with renin-angiotensin system inhibitors plus calcium channel blockers (CCBs) elicits beneficial effects on cardiovascular and renal events in hypertensive patients with high cardiovascular risks. In the present study, we hypothesized that CCB enhances the protective effects of an angiotensin II type 1 receptor blocker (ARB) against diabetic cerebrovascular-renal injury. Saline-drinking type 2 diabetic KK-A(y) mice developed hypertension and exhibited impaired cognitive function, blood-brain barrier (BBB) disruption, albuminuria, glomerular sclerosis and podocyte injury. These brain and renal injuries were associated with increased gene expression of NADPH oxidase components, NADPH oxidase activity and oxidative stress in brain and kidney tissues as well as systemic oxidative stress. Treatment with the ARB, olmesartan (10 mg/kg/day) reduced blood pressure in saline-drinking KK-A(y) mice and attenuated cognitive decline, BBB disruption, glomerular injury and albuminuria, which were associated with a reduction of NADPH oxidase activity and oxidative stress in brain and kidney tissues as well as systemic oxidative stress. Furthermore, a suppressive dose of azelnidipine (3 mg/kg/day) exaggerated these beneficial effects of olmesartan. These data support the hypothesis that a CCB enhances ARB-associated cerebrovascular-renal protective effects through suppression of NADPH oxidase-dependent oxidative stress in type 2 diabetes.

| S-EPMC3858271 | biostudies-literature

Project description:Overseas guidelines to manage hypertension recommend selecting different drugs depending on age, but no studies have investigated the relationship between drug selection and age- and sex-related differences, although such information may help to reduce the risk of cardiovascular mortality. The Azilsartan Circadian and Sleep Pressure--the First Study (ACS1) trial was a multicentered, randomized, open-label, two-parallel group study comparing the effects of an angiotensin II receptor blocker (azilsartan) and a calcium channel blocker (amlodipine). The present study is a post hoc analysis of ACS1 to investigate age- and sex-related differences in the antihypertensive effects between azilsartan and amlodipine. Azilsartan significantly reduced diastolic blood pressure in male patients younger than 60 years compared with amlodipine, but amlodipine significantly reduced systolic blood pressure in female patients 60 years and older compared with azilsartan. A randomized controlled trial to evaluate cardiovascular outcomes will demonstrate whether a diastolic blood pressure-lowering effect with azilsartan is significantly effective in male patients younger than 60 years.

| S-EPMC8032083 | biostudies-literature

Rationale for triple fixed-dose combination therapy with an angiotensin II receptor blocker, a calcium channel blocker, and a thiazide diuretic.

Project description:Hypertension is a growing global health problem, and is predicted to affect 1.56 billion people by 2025. Treatment remains suboptimal, with control of blood pressure achieved in only 20%-35% of patients, and the majority requiring two or more antihypertensive drugs to achieve recommended blood pressure goals. To improve blood pressure control, the European hypertension guidelines recommend that angiotensin II receptor blockers (ARBs) or angiotensin-converting enzyme inhibitors (ACEIs) are combined with calcium channel blockers (CCBs) and/or thiazide diuretics. The rationale for this strategy is based, in part, on their different effects on the renin-angiotensin system, which improves antihypertensive efficacy. Data from a large number of trials support the efficacy of ACEIs or ARBs in combination with CCBs and/or hydrochlorothiazide (HCTZ). Combining two different classes of antihypertensive drugs has an additive effect on lowering of blood pressure, and does not increase adverse events, with the ARBs showing a tolerability advantage over the ACEIs. Among the different ARBs, olmesartan medoxomil is available as a dual fixed-dose combination with either amlodipine or HCTZ, and the increased blood pressure-lowering efficacy of these two combinations is proven. Triple therapy is required in 15%-20% of treated uncontrolled hypertensive patients, with a renin-angiotensin system blocker, CCB, and thiazide diuretic considered to be a rational combination according to the European guidelines. Olmesartan, amlodipine, and HCTZ are available as a triple fixed-dose combination, and significant blood pressure reductions have been observed with this regimen compared with the possible dual combinations. The availability of these fixed-dose combinations should lead to improvement in blood pressure control and aid compliance with long-term therapy, optimizing the management of this chronic condition.

| S-EPMC3383291 | biostudies-other

Racial differences in blood pressure response to calcium channel blocker monotherapy: a meta-analysis.

Project description:BACKGROUND:A systematic literature review was conducted to determine whether US blacks and whites have differential blood pressure (BP) response to calcium channel blocker (CCB) monotherapy. METHODS:Six published studies made up the final cohort of eligible articles. Multiple treatment groups within some studies led to a total of eight sets of estimates for BP reduction with a total of 6,851 white or nonblack participants and 3,371 black participants. RESULTS:The pooled difference in systolic blood pressure (SBP) change between blacks and whites was -2.7 mm Hg (95% confidence interval (CI): -4.0, -1.3) with blacks having greater response. The difference in diastolic blood pressure (DBP) between blacks and whites was -0.4 mm Hg (95% CI: -1.0, 0.3) with blacks having greater response. Using a dichotomous outcome measure, whites were found to be just as likely as blacks to attain the DBP goal of <90 mm Hg or a 10 mm Hg or greater change (relative risk: 1.00 95% CI: 0.91, 1.11). In addition, examination of the continuous distribution of BP responses of whites and blacks showed over 90% overlap in treatment response. CONCLUSION:Assessment of differential response to CCB monotherapy by race in published data depends on choice of outcome metric. Nonetheless, the results of this systematic review indicate that BP response is qualitatively similar in US blacks and whites, suggesting that patient race is not likely to offer any clinical utility for decisions about the likely effect of this antihypertensive therapy.

| S-EPMC6414055 | biostudies-literature

Angiotensin II receptor blockers improve peripheral endothelial function: a meta-analysis of randomized controlled trials.

Project description:Objective(s)Several studies have assessed the effect of angiotensin II receptor blockers (ARBs) on peripheral endothelial dysfunction as measured by flow-mediated vasodilatation (FMD), a widely-used indicator for endothelial function. We conducted a meta-analysis to investigate the effect in comparison to placebo or no treatment and other antihypertensives.MethodsMEDLINE, Cochrane library and EMBASE were searched to September 2013 for randomized controlled trials (RCTs) that assessed the effect of ARBs versus placebo or no treatment and other antihypertensives (angiotensin-converting enzyme inhibitors (ACEIs), calcium channel blockers (CCBs), ?-blockers, diuretics) by forearm FMD. Furthermore, we also use meta-regression to analyze the relationship between the endothelial function and the duration of ARBs treatments.ResultsIn 11 trials including 590 patients, ARBs (n?=?315) significantly improved FMD (1.36%, 95% confidence internal [CI]:1.28 to 1.44) versus placebo or no treatment (n?=?275). In 16 trials that included 1028 patients, ARBs (n?=?486) had a significant effect (0.59%, 95% CI: 0.25 to 0.94) on FMD when compared with other antihypertensives (n?=?542). In 8 trials, ARBs (n?=?174) had no significant effect (-0.14%, 95% CI: -0.32 to 0.03) compared with ACEI (n?=?173). Compared with others, the benefits of ARBs, respectively, were 1.67% (95% CI: 0.65 to 0.93) in 7 trials with CCBs, 0.79% (95% CI: 0.42 to 1.01) with ?-blockers in 3 trials and 0.9% (95% CI: 0.77 to 1.03) with diuretics in 3 trials. Importantly, we found ARBs were less effective in a long time span (95% CI: -1.990 to -0.622) than the first 6 months (95% CI: -0.484 to 0.360).ConclusionsThis study shows that ARBs improve peripheral endothelial function and are superior to CCBs, ?-blockers and diuretics. However, the effect couldn't be maintained for a long time. In addition, there was no significant difference between ARBs and ACEI.

| S-EPMC3940822 | biostudies-literature

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