Beneficial effects of carvedilol on angiotensin-converting enzyme activity and renin plasma levels in patients with chronic heart failure.

OBJECTIVE

To assess the effects of carvedilol treatment on the renin-angiotensin system in patients with chronic heart failure (CHF).

BACKGROUND

Carvedilol improves survival of patients suffering from CHF but the effects of the drug on angiotensin-converting enzyme (ACE) activity, renin and aldosterone are not well characterized in patients receiving an ACE inhibitor.

METHODS

A randomized, multicenter, double-blind, 6-month, placebo-controlled study of carvedilol vs. placebo was conducted in 64 CHF patients. Circulating levels of ACE activity, active renin and aldosterone as well as left ventricular diameters and ejection fraction by echography were assessed.

RESULTS

During the study, left ventricular ejection fraction increased from 25+/-11% to 31+/-12% with carvedilol and from 27+/-12% to 28+/-12% with placebo (P=0.03). This beneficial effect was associated with marked blunting of active renin secretion (-53% in the carvedilol group vs.-13% in the placebo group, P=0.04). ACE activity was reduced by 30% in the carvedilol group (P=0.07 vs. placebo). Aldosterone was not changed.

CONCLUSION

Carvedilol markedly reduced the increase in active renin observed with time despite ACE-inhibitors and tended to decrease ACE activity. These findings may in part explain the beneficial actions of carvedilol and highlights the profound effect of betablockade on renin in patients already receiving ACE-inibitors.