Clinical study: hypertension
Evidence-based evaluation of calcium channel blockers for hypertension: Equality of mortality and cardiovascular risk relative to conventional therapy

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Abstract

Objectives

We present a meta-analysis based on three recent, substantial, randomized outcome trials and several smaller trials that compared calcium channel blockers (CCBs) with conventional therapy (diuretics or beta-blockers) or with angiotensin-converting enzyme (ACE) inhibitors

Background

There is continuing uncertainty about the safety and efficacy of CCBs in the treatment of hypertension. Previous meta-analyses conflict and suggest that CCBs increase myocardial infarction (MI) or protect from stroke.

Methods

Standard procedures for meta-analysis were used to analyze three major trials on 21,611 patients and another three lesser studies to a total of 24,322 patients.

Results

Calcium channel blockers have a strikingly similar risk of total and cardiovascular mortality and of major cardiovascular events to conventional therapy. Calcium channel blockers give a lower risk of nonfatal stroke (−25%, p = 0.001) and a higher risk of total MI (18%, p = 0.013), chiefly nonfatal (18%). After performing the Bonferroni correction for multiplicity, these p values become 0.004 and 0.052, respectively. When compared with ACE inhibitors in 1,318 diabetic patients, CCBs had a substantially higher risk of nonfatal (relative risk [RR] = 2.259) and total MI (RR = 2.204, confidence interval 1.501 to 3.238; p = 0.001 or 0.004 with Bonferroni correction). Total and cardiovascular mortality rates are similar. To confirm the hypothesis that ACE inhibitors are superior to CCBs in diabetic patients requires more trial data, especially with renal end points.

Conclusions

Mortality (total and cardiovascular) and major cardiovascular events with CCBs were apparently similar to those events seen with conventional first-line therapy (diuretics or beta-blockers). Stroke reduction more than balanced increased MI. In diabetics, CCBs may be less safe than ACE inhibitors.

Abbreviations

ABCD
Appropriate Blood pressure Control in Diabetes trial
ACE
angiotensin-converting enzyme
CASTEL
Cardiovascular Study of the Elderly
CCB
calcium channel blocker
CI
confidence interval
FACET
Fosinopril versus Amlodipine Cardiovascular Events Trial
MI
myocardial infarction
MIDAS
Multicenter Isradipine Diuretic Atherosclerosis Study
RR
relative risk
STOP-Hypertension
Swedish Trial in Old Patients with Hypertension

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This study was entirely supported by the Medical Research Council of South Africa (to Dr. Opie).