BACKGROUND: Calcium channel blockers (CCBs) are more effective than placebo in lowering blood pressure and in preventing subsequent cardiovascular outcomes. However, observational studies of short-acting CCBs and controlled trials of long-acting CCBs have shown that although blood pressure is controlled, cardiovascular event rates increase. The authors performed a meta-analysis of randomized controlled trials comparing CCBs with first-line antihypertensives regarding their effects on cardiovascular events. population studied The analysis included 9 studies involving 27,743 patients. The mean age range was 53.9 to 76.1 years. Both men and women were represented in the analysis. Follow-up was 2 to 7 years with an estimated total follow-up of 120,000 person-years.
STUDY DESIGN AND VALIDITY: This is a meta-analysis of the existing literature. Studies were identified for inclusion through a systematic search of MEDLINE. To be included the randomized trials had to have more than 100 participants, follow-up longer than 2 years, compare CCBs with other first-line agents, and evaluate the effect on cardiovascular outcomes. The studies compared CCBs with diuretics, b-blockers, angiotensin-converting enzyme inhibitors, and clonidine. Two investigators independently abstracted data. Outcome data were analyzed by intention to treat except in one study that consisted of 429 patients. Tests for heterogeneity were performed. The meta-analysis is well done although limited by the quality of the included studies. Each of the 9 studies in the analysis has a limitation. Five of the studies were open design, and in 4 studies the authors had to contact investigators to obtain information on the primary outcomes. Two studies dealt primarily with patients with diabetes. In one study randomization favored the CCB arm, while in another the non-CCB arm had a more favorable baseline. The dropout rate for the studies ranged from 7% to 60%. A variety of sensitivity analyses were done to determine if one study, one drug type, or one type of patient profile contributed to the results. This did not appear to be the situation, although there was insufficient power in some of the sensitivity analyses to answer this question confidently.
OUTCOMES MEASURED: The outcomes measured were changes in systolic and diastolic blood pressure, acute myocardial infarctions, congestive heart failure, stroke, and all-cause mortality. The authors also evaluated the effect of treatment on the combined outcome of major cardiovascular events including acute myocardial infarction, congestive heart failure, stroke, and cardiovascular mortality.
RESULTS: CCBs lowered both systolic and diastolic blood pressure comparably with first-line agents. CCBs had a higher risk of acute myocardial infarction (odds ratio [OR]=1.26; 95% confidence interval [CI], 1.11-1.43), congestive heart failure (OR=1.25; 95% CI, 1.07-1.46), and major cardiovascular events (OR=1.10; 95% CI, 1.02-1.18). CCBs were comparable with other agents for reducing the risk of stroke (OR=0.90; 95% CI, 0.80-1.02) and all-cause mortality (OR=1.03; 95% CI, 0.94-1.13).
CCBs should not be used as first-line antihypertensive therapy in patients at risk for coronary heart disease and heart failure. Although CCBs lower blood pressure, their effect on preventing of acute myocardial infarction, congestive heart failure, and overall cardiovascular mortality is less favorable than with first-line therapies. The risk of stroke and overall mortality is comparable with first-line therapy. In targeted populations, such as Asians or those with isolated hypertension with no risk factors for coronary artery disease, CCBs might be considered as first-line agents. This meta-analysis supports the recommendation of the Sixth Report on Prevention, Detection, Evaluation and Treatment of High Blood Pressure: Use diuretics and b-blockers as first-line agents.