Abstract 2912: Effect of β1 389 Arg/Gly α2c 322–325 Wt/Del Genotypes on Adjudicated Hospitalizations in the BEST Trial
The 2708 patient Beta Blocker Evaluation of Survival Trial (BEST) contained a 1040 patient DNA bank. One DNA substudy approved by the BEST DNA oversight committee was an adrenergic receptor polymorphism proposal testing the hypothesis that common gene variants in the β1-(codon 389 Arg→Gly) and α2-(322–325 wild type→deletion) adrenergic receptors influence the treatment effects of bucindolol. The original method of determining hospitalization type in BEST was via investigator case report forms (CRFs), which captured whether a hospitalization was due to worsening heart failure or not. Recently the BEST nine member endpoints committee has completed an adjudication of all 5086 hospitalizations, classifying them into cardiovascular (CV), the sub CV category of heart failure (HF), non-CV and other subcategories. These data as bucindolol/placebo time to event (TTE) hazard ratios (95% confidence intervals) are reported in the 2708 patient entire cohort, as well as in the 1040 DNA substudy by genotype: (H = hospitalization; M = all cause mortality; E = # events; P = placebo; B = bucindolol; * = p <0.05; † = p<0.01) For HFH, CRF data gave similar treatment effects.
In the entire cohort, bucindolol highly significantly reduced the time to CVH and first event HFH, HFH/pt and HFH days/pt;
there was no effect of bucindolol on non-CV hospitalizations;
the β1 389 Arg/Gly polymorphism substantially influenced bucindolol treatment effects on CVH and HFH;
the α2c 322–325 Wt/Del polymorphism did not affect bucindolol treatment effects on CVHTTE, HFHTTE, or HFH/pt, but the wild type receptor variant reduced HFH days/pt and MTTE.