Aspirin impairs reverse myocardial remodeling in patients with heart failure treated with beta-blockers.
OBJECTIVE
We hypothesized that aspirin (ASA) might alter the beneficial effect of beta-blockers on left ventricular ejection fraction (LVEF) in patients with chronic heart failure.


BACKGROUND
Aspirin blunts the vasodilation caused by both angiotensin-converting enzyme (ACE) inhibitors and beta-blockers in hypertensive patients and in patients with heart failure. Several studies suggest that ASA also blunts some of beneficial effects of ACE inhibitors on mortality in patients with heart failure. To our knowledge, there have been no data evaluating the possible interaction of ASA and beta-blockers on left ventricular remodeling 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-blind, randomized, placebo-controlled, multicenter, dose-response evaluation of carvedilol in patients with chronic stable symptomatic heart failure. Multivariate analysis was performed to determine if aspirin independently influenced the improvement in LVEF.


RESULTS
Over all randomized patients (n = 293), LVEF improved 8.2 +/- 0.8 ejection 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 placebo or carvedilol groups. The effect of ASA became more significant on multivariate analysis. The change in LVEF was also influenced by carvedilol dose, etiology of heart failure, baseline heart rate, EF and coumadin use. The detrimental effect of ASA on the improvement in LVEF was dose-related and was present in both placebo and carvedilol groups, although the effect was 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 carvedilol. The specific mechanism(s) underlying this interaction are unknown and further studies are needed to provide additional understanding of the molecular basis of factors influencing reverse remodeling in patients with heart failure.
Lindenfeld
J
J
Division of Cardiology, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA. JoAnn.Lindenfeld@UCHSC.edu
Robertson
A D
AD
Lowes
B D
BD
Bristow
M R
MR
D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage*; D002227:Carbazoles / Q000008:administration & dosage / Q000037:antagonists & inhibitors*; D000077261:Carvedilol; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005260:Female; D006333:Heart Failure / Q000188:drug therapy*; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D011412:Propanolamines / Q000008:administration & dosage / Q000037:antagonists & inhibitors*; D012189:Retrospective Studies; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy*; D016277:Ventricular Function, Left / Q000187:drug effects; D020257:Ventricular Remodeling / Q000187:drug effects*
D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol