BACKGROUND: Management guidelines for heart failure recommend ACE-I and beta-blockers. The perception of difficult up-titration might have added to the slow uptake of beta-blockers despite their mortality and morbidity benefits. AIMS: CARMEN offered a possibility to study safety and tolerability of enalapril against carvedilol and their combination. METHODS:Five hundred and seventy-two patients were blindly up-titrated on carvedilol (target 25 mg bid) and/or enalapril (target 10 mg bid), and continued for 18 months. In the combination arm, carvedilol was up-titrated before enalapril. RESULTS: There was no group related difference in adverse events during up-titration. Withdrawal rates were 31, 30 and 30%, and serious adverse events 28, 29 and 34% in the combination, carvedilol and enalapril arms. Mortality was similar in all groups (all-cause N=14, 14 and 14; cardiovascular N=9, 13 and 14). All-cause and cardiovascular hospitalizations occurred in 26, 27 and 32%, and in 12, 16 and 22% in the combination, carvedilol and enalapril arms, respectively. CONCLUSION: The safety profile was similar in all treatment arms. In contrast to common perception, there was no difference in tolerability between the ACE-I and carvedilol. This result is even more remarkable as the high prestudy use of ACE-I (65%) might have introduced a bias by selecting ACE-I tolerant patients, who were only switched from their former ACE-I to enalapril.
RCT Entities:
BACKGROUND: Management guidelines for heart failure recommend ACE-I and beta-blockers. The perception of difficult up-titration might have added to the slow uptake of beta-blockers despite their mortality and morbidity benefits. AIMS: CARMEN offered a possibility to study safety and tolerability of enalapril against carvedilol and their combination. METHODS: Five hundred and seventy-two patients were blindly up-titrated on carvedilol (target 25 mg bid) and/or enalapril (target 10 mg bid), and continued for 18 months. In the combination arm, carvedilol was up-titrated before enalapril. RESULTS: There was no group related difference in adverse events during up-titration. Withdrawal rates were 31, 30 and 30%, and serious adverse events 28, 29 and 34% in the combination, carvedilol and enalapril arms. Mortality was similar in all groups (all-cause N=14, 14 and 14; cardiovascular N=9, 13 and 14). All-cause and cardiovascular hospitalizations occurred in 26, 27 and 32%, and in 12, 16 and 22% in the combination, carvedilol and enalapril arms, respectively. CONCLUSION: The safety profile was similar in all treatment arms. In contrast to common perception, there was no difference in tolerability between the ACE-I and carvedilol. This result is even more remarkable as the high prestudy use of ACE-I (65%) might have introduced a bias by selecting ACE-I tolerant patients, who were only switched from their former ACE-I to enalapril.
Authors: Meaghan Lunney; Marinella Ruospo; Patrizia Natale; Robert R Quinn; Paul E Ronksley; Ioannis Konstantinidis; Suetonia C Palmer; Marcello Tonelli; Giovanni Fm Strippoli; Pietro Ravani Journal: Cochrane Database Syst Rev Date: 2020-02-27
Authors: Saurav Chatterjee; Giuseppe Biondi-Zoccai; Antonio Abbate; Fabrizio D'Ascenzo; Davide Castagno; Benjamin Van Tassell; Debabrata Mukherjee; Edgar Lichstein Journal: BMJ Date: 2013-01-16
Authors: John J V McMurray; Milton Packer; Akshay S Desai; Jim Gong; Martin P Lefkowitz; Adel R Rizkala; Jean Rouleau; Victor C Shi; Scott D Solomon; Karl Swedberg; Michael R Zile Journal: Eur J Heart Fail Date: 2013-04-05 Impact factor: 15.534