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.


CONCLUSIONS
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.
Cohen Solal
Alain
A
Service de Cardiologie, Centre Hospitalier Universitaire Beaujon, Assistance Publique - Hôpitaux de Paris, Faculté Xavier Bichat, Hôpital Beaujon, 100 Boulevard du Général Leclerc, 92110 Clichy, France. alain.cohen-solal@bjn.ap-hop-paris.fr
Jondeau
Guillaume
G
Beauvais
Florence
F
Berdeaux
Alain
A
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000368:Aged; D015415:Biomarkers / Q000097:blood; D002227:Carbazoles / Q000627:therapeutic use*; D000077261:Carvedilol; D002908:Chronic Disease; D003971:Diastole / Q000187:drug effects; D004311:Double-Blind Method; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000378:metabolism* / Q000503:physiopathology; D006352:Heart Ventricles / Q000187:drug effects / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000187:drug effects* / Q000378:metabolism*; D011412:Propanolamines / Q000627:therapeutic use*; D012083:Renin / Q000187:drug effects* / Q000378:metabolism*; D013318:Stroke Volume / Q000187:drug effects; D013599:Systole / Q000187:drug effects; D016896:Treatment Outcome; D016277:Ventricular Function, Left / Q000187:drug effects
D000319:Adrenergic beta-Antagonists; D015415:Biomarkers; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol; D007703:Peptidyl-Dipeptidase A; D012083:Renin