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

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.