The Potential Role of Calcium Antagonists in the Management of Congestive Heart Failure

Abstract

First-generation calcium antagonists have been used in patients with congestive heart failure with rather disappointing results. Therefore, second-generation dihydropyridine calcium-channel blockers, such as felodipine and lacidipine, have been developed that may be beneficial in congestive heart failure owing to their high vasoselectivity and more favorable neurohumoral modulation. The effects of lacidipine in patients with congestive heart failure, who remain symptomatic despite receiving long-term therapy with angiotensin-converting enzyme inhibitors, digoxin, and diuretics, were investigated during a prospective, double-blind, randomized, placebo-controlled, parallel-group study. Twenty-five patients were randomized to receive either lacidipine (4 mg once daily; 12 patients) or placebo (once daily; 13 patients). After 8 weeks of treatment patients receiving lacidipine showed a significantly higher increase in cardiac output (p < 0.01), and a significantly greater reduction in vascular resistance (p < 0.02) than those patients in the placebo group. No significant changes were observed in filling pressures and heart rate. The arteriovenous oxygen content difference was significantly reduced in the lacidipine group (p < 0.01) without significant changes in arterial oxygenation, suggesting an increase in flow that was not a result of pulmonary shunting. Further peak oxygen consumption during cardiopulmonary exercise testing increased significantly in the lacidipine patients (p < 0.02). These beneficial effects were achieved without significant changes in neurohumoral parameters. Analysis of right and left ventricular ejection fractions revealed no cardiodepressant effects. Lacidipine was well tolerated during the course of the study, and adverse reactions were minor. These data suggest that lacidipine has a promising profile for the treatment of congestive heart failure patients, and that further investigation with second-generation dihydropyridines in the field of congestive heart failure appears warranted.