Abstract: 1085-74
　

Do Patients Necessarily Have to Start With an Angiotension Converting Enzyme Inhibitor in the Treatment of Heart Failure? Results of the CARMEN (Carvedilol ACE Inhibitor Remodeling Mild CHF EvaluatioN) Study

Willem J. Remme, Guenther Riegger, Per Hildebrandt, Michel Komajda, Marco Bobbio, Jordi Soler-Soler, Wybren Jaarsma, Stuart Pocock, Lars Ryden, on behalf of the CARMEN investigators

Sticares, Rotterdam, The Netherlands

Topic: Myocardial Function/Heart Failure--Clinical

Background: Treatment guidelines for chronic heart failure (CHF) recommend ACE-inhibitor (ACE-I) as first-line treatment and ß-blockers are to be added in case patients remain symptomatic. This paradigm, based on historical grounds, enforces polypharmacy and prevents an individualized approach to the treatment of CHF. The aims of the CARMEN trial were to challenge this paradigm by comparing the effect on cardiac remodeling of the ACE-I Enalapril (E) against Carvedilol (C) a combined ß1/ß2- blocker with additional α1-receptor blockade and antioxidant properties.

Methods: CARMEN is a parallel-group, 3-arm, double-dummy, multi-center study conducted in 13 European countries. Patients were randomized to C&E, C or E treatment, uptitrated on C to 25mg (50mg in patients ≧ 85kg) bid target dose and/or E to 10mg bid target dose, and continued for 18 months. In the C&E treated arm, C was uptitrated first. Effects on left ventricular (LV) remodeling were assessed by serial transthoracic echocardiography (biplane, Simpson) at baseline, months 6, 12 and 18 at a central core laboratory.

Results: The ITT population included 479 mild (NYHA II = 65%, LV ejection fraction (EF) <40%) CHF patients (C&E = 158; C = 161; E = 160), 81% male, mean age 62 years. LV end systolic volume index (LVESVI) was reduced by 5.4 ml/m2 (p=0.0015), LV end diastolic volume index by 5.0 ml/m2 (p=0.0046) and LVEF increased by 2.3% (p=0.0022) at month 18 for the primary comparison favoring C&E versus E. The second primary comparison favored C versus E, although differences were not significant. However, in the within-group comparison C significantly reduced LVESVI by 2.8 ml/m2 (p=0.018) compared to baseline, whereas no changes were observed in E, and LVESVI decreased by 6.3 ml/ m2 (p=0.0001) in C&E. All three arm showed very similar safety profiles and withdrawal rates.

Conclusion: The CARMEN results confirm the current treatment guidelines and provide an immediate mandate for prescribing the combination of ACE-I and C in mild CHF patients. However, as C was safely initiated before ACE-I and resulted in reversed LV remodeling, one might challenge the historical sequence of ACE-I as first-line therapy and start treatment with Carvedilol before ACE-I.


Citation: Supplement to Journal of the American College of Cardiology, March 19, 2003, Vol. 41, Issue 6, Suppl. A