lacidipine and Heart-Failure

To evaluate the efficacy and safety of the second generation dihydropyridine calcium channel blocker lacidipine in patients with heart failure.. Placebo controlled, parallel group, double blind study over 8 weeks.. General community hospital in Breda, The Netherlands.. A random sample was studied of 25 outpatients with symptoms of mild to moderate heart failure, despite treatment with diuretics, digoxin, and angiotensin converting enzyme inhibitors. Their mean age was 65 years, with mean left ventricular ejection fraction of 0.24 and a peak oxygen consumption of 14.4 ml/min/kg. Two patients dropped out on lacidipine, one patient on placebo.. Treatment with lacidipine 4 mg once daily or placebo for eight weeks.. Cardiopulmonary exercise testing, invasive haemodynamics, and plasma neurohormones.. Treatment with lacidipine 4 mg once daily, as compared to placebo treatment, significantly improved peak oxygen consumption (P < 0.02), cardiac index (P < 0.01), and stroke volume (P < 0.03) paralleled by a decrease in systemic vascular resistance (P < 0.03) and arteriovenous oxygen content difference (P < 0.01). Plasma noradrenaline, plasma renin activity, and aldosterone values did not differ between lacidipine and placebo.. This second generation dihydropyridine may be of value as an adjunct to standard treatment in congestive heart failure patients.

Topics: Aged; Aldosterone; Angiotensin-Converting Enzyme Inhibitors; Calcium Channel Blockers; Digoxin; Dihydropyridines; Diuretics; Double-Blind Method; Drug Therapy, Combination; Female; Heart Failure; Hemodynamics; Humans; Male; Middle Aged; Norepinephrine; Oxygen Consumption; Prospective Studies; Renin; Stroke Volume; Vascular Resistance

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.

Topics: Aged; Calcium Channel Blockers; Dihydropyridines; Double-Blind Method; Epinephrine; Exercise Test; Female; Heart Failure; Hemodynamics; Humans; Male; Middle Aged; Norepinephrine; Prospective Studies; Renin