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CLINICAL STUDY: HYPERTENSION

Evidence-based evaluation of calcium channel blockers for hypertension

Equality of mortality and cardiovascular risk relative to conventional therapy

Lionel H. Opie, MD, DPhil, DSc, FACC^*,* and Robert Schall, PhD

^* Hatter Institute, Department of Medicine, Cape Heart Center, University of Cape Town Medical School, Cape Town, South Africa
Quintiles ClinData, Bloemfontein, South Africa

Manuscript received May 7, 2001; revised manuscript received August 15, 2001, accepted October 19, 2001.

^* Reprint requests and correspondence: Dr. Lionel H. Opie, Cape Heart Center, University of Cape Town Medical School, Observatory 7925, Cape Town, South Africa.
Opie{at}capeheart.uct.ac.za

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 and Acronyms   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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