Eur J Heart Fail. 2004 Jun;6(4):467-75 Institut de Cardiologie， Centre Hospitalier GH Pitie-Salpetriere， 47-83 Bld de l"Hopital， 75013， Paris Cedex 13， France. Veronique.villareal@chups.jusssieu.fr

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.