The calcium channel blocker controversy in perspective.

Abstract

Periodically in the history of hypertensive therapy there have been minor storms that have significantly affected the utilization of entire classes of agents. The first storm struck with the case-control studies suggesting that reserpine was associated with an increased risk of carcinoma of the breast, a claim subsequently disproved by a number of other studies. The second storm was initiated by a subanalysis of the Multiple Risk Factor Intervention Trial (MRFIT), from which it was inferred that, in a subset of hypertensive patients, diuretic treatment may have been harmful rather than beneficial. Despite this claim and other speculations, diuretics-especially at low doses-remain a gold standard of antihypertensive therapy. Recently, a third storm has developed in the field of antihypertensive therapy: a case-control study report and a non-randomized cohort study have questioned the use of calcium channel blockers in hypertension. The case-control study suffers from the limitations inherent in this study design, which often gives rise to conflicts and contradiction. In fact, another case-control study published in 1995 reached exactly the opposite conclusions and claimed that calcium channel blockers were associated with significantly less myocardial infarction than traditional antihypertensive therapy. A meta-analysis was also presented as supporting the non-randomized studies questioning the safety of calcium channel blockers. However, it refers to patients with coronary heart disease, not to patients with hypertension, and also combined studies performed with different aims, and data from short-term and long-term studies using short-acting formulations of calcium channel blockers. The controversies generated by these reports have gone well beyond their scientific merit. For final judgement we should wait for well-designed prospective studies, several of which are under way. For the time being, there is no reason to change the current practice of antihypertensive therapy, as summarized in the recommendations of both the United States Joint National Committee and the World Health Organization/International Society of Hypertension Committee, that is, diuretics and beta-blockers are among those antihypertensive agents with clearly proven benefits in mortality-morbidity studies, but calcium channel blockers as well as ACE inhibitors and alpha-blockers can also be used profitably in the treatment of hypertension.