Tolerability of carvedilol and ACE-inhibition in mild heart failure.: Results of CARMEN (Carvedilol ACE-Inhibitor Remodelling Mild CHF EvaluatioN)

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. (C) 2004 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.