Abstract 2177: Differential Effects of β-1 Polymorphisms on Mortality, Hospitalizations, and Myocardial Infarctions with Bucindolol Therapy.
Background: The Beta-Blocker Evaluation of Survival Trial (BEST) contained a DNA substudy that included the analysis of β-1 adrenergic receptor (AR) polymorphisms. Advanced heart failure patients who are homozygous Arg at codon 389 of the β-1 AR have a much better response to bucindolol therapy, in terms of reductions in all-cause mortality and heart failure hospitalizations, than do those who are Gly carriers (Gly homozygotes or heterozygotes). The goal of this study was to determine the effects of codon 389 β-1 polymorphisms on myocardial infarction, a prespecified BEST secondary endpoint, in response to bucindolol therapy.
Methods: BEST was a multicenter, randomized, double-blind, placebo-controlled trial of bucindolol in patients with advanced heart failure. Events were adjudicated by an end-points committee. The DNA substudy enrolled 1040 patients. Data were analyzed using a Cox Proportional Hazards model.
Results: The β-389 Arg/Arg polymorphism is associated with a better mortality and heart failure hospitalization rate in response to bucindolol therapy, as previously reported. However, bucindolol decreases myocardial infarctions independent of β-1 polymorphisms.
Conclusions: Heart failure patients with the β1 Arg/Arg polymorphism have an enhanced response to bucindolol for mortality and heart failure hospitalization, but not for myocardial infarction. This suggests that the therapeutic mechanism by which bucindolol decreases myocardial infarction is independent of the mechanism(s) by which it lowers mortality and heart failure hospitalizations.