Safety of calcium antagonists in patients with congestive heart failure.

Continuing high morbidity and mortality have spurred an ongoing search for new therapeutic agents for patients with congestive heart failure. Calcium antagonists (CAs) have been under active investigation in patients with heart failure since their introduction into clinical medicine, because their anti-ischemic and vasodilator properties were thought to be of potential benefit in this patient population. However, review of published clinical trials of CAs in patients with heart failure reveals that some of these drugs are associated with detrimental effects, including acute hemodynamic deterioration, increased symptoms of heart failure, and increased mortality. The adverse effects of short-acting CAs in patients with heart failure include negative inotropic effects and neurohormonal activation. Long-acting CAs, such as amlodipine and felodipine, had fewer negative inotropic effects, showed less evidence of neurohormonal activation, and were better tolerated in clinical trials. Amlodipine, in combination with an angiotensin-converting enzyme inhibitor, had a neutral effect in patients with ischemic heart failure and an unexplained benefit in a subgroup of patients with non-ischemic cardiomyopathy. Although the preliminary experience with long-acting dihydropyridine CAs in heart failure has been encouraging, safety concerns raised by past trials dictate that no CA can be recommended for the treatment of heart failure at this time.