Calcium channel blockers and hypertension: evolving perspective--1996

In recent years, calcium channel blockers (CCBs) have been used extensively in the United States and elsewhere as antihypertensive agents, and their availability has been an important advance in the management of hypertension. As antihypertensive agents, the CCBs thus appear considerably more versatile than most previous vasodilators. The available studies indicate that CCBs are metabolically neutral and do not exacerbate dyslipidemia or impair glucose tolerance. In contrast to diuretics and beta-blockers, CCBs do not appear to alter insulin sensitivity. The CCBs also differ from previous vasodilators because of their favorable accompanying effects on the heart and kidney. Despite the attributes of CCBs enumerated earlier, a number of recent retrospective analyses by Psaty et al. (JAMA 1995;274:620-625) have suggested that CCBs may be detrimental and may promote adverse cardiovascular events. I have recently reviewed the results of Psaty's meta-analysis and report (Arch Intern Med 1995;155: 2150-2156). I have emphasized that it is the rate of drug delivery into the systemic circulation that produces profound effects on the hemodynamic and neurohumoral responses to a dihydropyridine CCB drug. During chronic treatment with dihydropyridines, major fluctuations in blood pressure (rapid onset and offset of antihypertensive effects) during the dosing interval may persist for drugs and formulations that are short acting. In contrast, slow-release formulations of otherwise rapidly absorbed dihydropyridines achieve a more gradual and sustained antihypertensive effect. It is probable that newer CCB formulations that do not provoke intermittent sympathetic activation and do not evoke a cardioacceleratory response would not be expected to promote adverse cardiovascular events.