Aspirin impairs reverse myocardial remodeling in patients with heart failure treated with beta-blockers

OBJECTIVES We hypothesized that aspirin (ASA) might alter the beneficial ef fect of beta-blockers on left ventricular ejection fraction (LVEF) in patie nts with chronic heart failure. BACKGROUND Aspirin blunts the vasodilation caused by both angiotensin-conve rting enzyme (ACE) inhibitors and beta-blockers in hypertensive patients an d in patients with heart failure. Several studied suggest that ASA also blu nts some of beneficial effects of ACE inhibitors on mortality, in patients with heart failure. To our knowledge, there have been no data evaluating th e possible interaction of ASA and beta-blockers on left ventricular remodel ing in patients with heart failure. METHODS We retrospectively evaluated patients entered into the Multicenter Oral Carvedilol Heart failure Assessment (MOCHA) trial, a 6-month, double-b lind, randomized, placebo-controlled, multicenter, dose-response evaluation of carvedilol in patients with chronic stable symptomatic heart failure. M ultivariate analysis was performed to determine if aspirin independently in fluenced the improvement in LVEF. RESULTS Over all randomized patients (n = 293), LVEF improved 8.2 +/- 0.8 e jection fraction (EF) units in ASA nonusers and 4.5 +/- 0.7 EF units in ASA users (p = 0.005). In subjects randomized to treatment with carvedilol (n = 231), LVEF improved 9.5 +/- 0.9 EF units in ASA nonusers and 5.8 +/- 0.8 EF units in ASA users (p = 0.02). In subjects randomized to treatment with placebo (n = 62), LVEF improved 2.8 +/- 1.2 EF units in ASA nonusers and 0. 5 +/- 1.4 EF units, in ASA users (p = 0.20). Aspirin did not significantly affect the heart rate or systolic blood pressure response in either the pla cebo or carvedilol groups. The effect of ASA became more significant on mul tivariate analysis. The change in LVEF was also influenced by, carvedilol d ose, etiology of heart failure, baseline heart rate, EF and coumadin use. T he detrimental effect of ASA on the improvement in LVEF was close-related a nd was present in both placebo and carvedilol groups, although the effect w as statistically significant only in the much larger carvedilol group. CONCLUSIONS Aspirin significantly affects the changes in LVEF over time in patients, with heart failure and systolic dysfunction treated with carvedil ol. The specific mechanism(s) underlying this interaction are unknown and f urther studies are needed to provide additional understanding of the molecu lar basis of factors influencing reverse remodeling in patients with heart failure. (J Am Coll Cardiol 2001;38:1950-6) (C) 2001 by the American Colleg e of Cardiology.