Abstract: 1184-73 |
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Replacement
of Angiotensin Converting Enzyme Inhibition by Carvedilol Results
in Long-Term Reversed Left Ventricular Remodeling in Mild Heart
Failure and Is Well Tolerated: Results of the CARMEN (Carvedilol
Ace-inhibitor Remodeling in Mild heart failure EvaluatioN) Study
Topic: Myocardial Function/Heart Failure--Clinical Background: In chronic heart failure (CHF), the effect of β-blockade on mortality, morbidity and cardiac remodeling have always been evaluated in addition to ACE-I. It is unknown whether the combination is mandatory or whether in terms of remodeling ACE-I can successfully be replaced by β-blockade. CARMEN compared the effect on remodeling of the ACE-I Enalapril (E) against Carvedilol (C), a combined β1 /β2 -blocker with additional a1-receptor blockade and anti-oxidant properties. Methods: A parallel-group, 3-arm, double-dummy, multi-center study was conducted in 13 European countries. Patients were randomized to C &E, C and E treatment, uptitrated on C to 25mg BID target dose and/or E to 10mg BID target dose, and continued for 18 months. Earlier ACE-I and β-blocking treatment was stopped prior to randomization. In the C&E arm, C was uptitrated first. Effects of left ventricular (LV) remodeling were assessed by transthoracic echocardiography (biplane) at baseline, months 6, 12 and 18 at a central core laboratory. Results: 572 mild CHF patients, mean age 62 years, 81% males, were randomized. Of these, 65% (N=374) had been on ACE-I treatment prior to the study start, whereas only 6% were on β-blockade. A subgroup analysis of the primary endpoint in former ACE-I users showed that LV end-systolic volume index was reduced at month 18 by 4.7 ml/m2 (p=0.006) in the C group (n=103) and by 6.0 ml/m2 (p=0.001) in the C&E group (n=114) from baseline. In contrast, in the E group (n=101) it increased by 0.6 ml/m2 (ns). The overall safety and tolerability profiles were comparable. In groups C&E, C and E adverse events occurred in 76%,75% and 74 %, respectively, whereas similar percentages of patients completed treatment (74%,70% and 72% respectively). Conclusions:Combination therapy (C&E) gave best results. However, replacement of ACE-I with C also resulted in significant reversal of cardiac remodeling with sustained, long-term reductions in LV volumes, in contrast to ongoing ACE-I alone. Despite a change in therapy, C patients did not experience more adverse events and a similar number of patients completed the study. Therefore, Carvedilol might be regarded as possible alternative to ACE-I in mild CHF patients.
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