Cardiovascular Pharmacology I| Volume 21, ISSUE 8, SUPPLEMENT , S49, August 2015

Bucindolol Prevents Atrial Flutter via the Beta-1 389 Arg/Gly Adrenergic Receptor Polymorphism


      Bucindolol, a beta-blocker and sympatholytic agent, has been shown to decrease incident atrial fibrillation (AF) in HFrEF patients in the Beta-Blocker Evaluation if Survival Trial (BEST). The goal of the current analysis was to assess whether bucindolol prevented atrial flutter (AFL) to the same degree as AF in BEST.


      This retrospective analysis was performed from BEST, which enrolled 2,708 NYHA class III or IV patients and included a 1040 patient DNA substudy that genotyped patients for the β1 -AR 389 Arg/Gly polymorphism.


      In BEST there were 17 patients with AFL and 303 patients with AF on their pre-randomization baseline ECG. In patients with baseline AFL, bucindolol was associated with a higher rate of reversion to sinus rhythm compared to placebo (bucindolol 8/9 (89%) vs. placebo 2/8 (25%); p = 0.0075). In patients who entered the trial not in AF or AFL, there were a total of 45 incident episodes of AFL during the trial, with fewer new onset AFL cases in the bucindolol group [bucindolol 17/1193 (1.4%) vs. Placebo 28/1182 (2.4%); HR = 0.55 (95% CI 0.30, 1.01)]. This prevention of AFL was similar to previous reports of AF prevention by bucindolol and, therefore, AF and AFL were grouped into one endpoint (AFL/AF). There was significantly less new onset AFL/AF with bucindolol compared to placebo [bucindolol 88/1193 (7.4%) vs. placebo 137/1182 (11.6%); HR 0.58 (95% CI 0.45, 0.76)]. In the BEST DNA substudy, prevention of AFL/AF was observed exclusively in the β1 Arg/Arg subgroup [HR 0.29(0.14,0.60)] compared to the β1 Gly carrier group [HR 0.91 (0.53, 1.56)] with a significant interaction between the genotype and treatment (p = 0.019).


      Bucindolol appears to prevent atrial flutter to a similar degree and by a similar mechanism as atrial fibrillation and, therefore, grouping atrial flutter with atrial fibrillation appears to be a legitimate endpoint in HFrEF AF prevention trials.