Calcium channel blockers in chronic heart failure. The risks of "physiologically rational" therapy.

A few observations and much reasoning leads to error; many observations and a little reasoning to truth.-Alexis Carrell oncerns have been raised about safety of calcium channel blockers in patients with heart failure since their introduction into cardiovascular medicine more than 25 years ago. By inhibiting the influx of calcium into myocardial cells, calcium channel-blocking drugs can depress contrac-tility in both experimental systems and the clinical setting. The magnitude of this effect is enhanced when these drugs are combined with other negative inotropic agents (e.g., ,8-blockers) or when they are administered to patients with impaired ventricular function.1,2 Patients with heart failure are particularly susceptible to the cardiodepressant actions of calcium channel blockers because the failing heart has a profound defect in the delivery of calcium to the contractile proteins.3 In addition, the sympathetic reflexes that normally function to counteract the negative inotropic effects of these drugs are markedly attenuated in chronic heart failure.4 As a result, both See p 1954 hemodynamic and clinical deterioration have been reported during short-and long-term therapy with verapamil, nifedipine, diltiazem, and nicardipine in patients with chronic heart failure.2 Some of these events (pulmonary edema and cardiogenic shock) have been life threatening.5 Despite concerns raised by these experimental and clinical observations, calcium channel blockers are widely used in patients with impaired cardiac func-The opinions expressed in this editorial comment are not necessarily those of the editors or of the American Heart Association. tion. Of the 2,500 patients with mild-to-moderate heart failure enrolled in the Studies of Left Ventric-ular Dysfunction Trial (SOLVD) sponsored by the National Institutes of Health, 30-35% were treated with a calcium channel blocker in addition to digitalis and diuretics (Dr. B. Pitt and Dr. S. Yusuf on behalf of the SOLVD Investigators, personal communication). Although the calcium channel blockers were generally prescribed for the treatment of the underlying coronary artery disease rather than for heart failure, these agents were used much more frequently in this study than were ,-blockers, another class of antianginal drug, which were used in only 5-10%. This fourfold greater use of calcium channel blockers is difficult to explain because 18-blockers improve the long-term outcome of patients with left ventricular dysfunction due to ischemic heart disease,6 whereas calcium channel blockers have been reported to exert unfavorable effects in this high-risk subset.7 Despite these findings, most physicians believe that calcium channel blockers are safer than 13-blockers in patients with compromised ventricular …