Abstract 15679: Phase II Trial of Pharmacogenetic Guided Beta-Blocker Therapy With Bucindolol vs. Metoprolol for the Prevention of Atrial Fibrillation/Flutter in Heart Failure: GENETIC-AF AF Burden Substudy

• Published in: Circulation (New York, N.Y.) N.Y.), 2018-11, Vol.138 (Suppl_1 Suppl 1), p.A15679-A15679
• Main Authors: Piccini, Jonathan P, Abraham, William T, Healey, Jeff S, Van Veldhuisen, Dirk J, Sauer, William, Anand, Inder, White, Michel, Wilton, Stephen B, Along, Ryan G, Ziegler, Paul D, Davis, Gordon, Dufton, Christopher, Marshall, Debra, Bristow, Michael R, Connolly, Stuart
• Format: Article
• Language: English
• ISSN: 0009-7322; 1524-4539

IntroductionBeta-blockers lower the risk for developing atrial fibrillation (AF) in heart failure (HF) with reduced ejection fraction. Bucindolol is a nonselective beta-blocker/mild vasodilator with the unique properties of sympatholysis and ADRB1 Arg389 inverse agonism. GENETIC-AF, a pharmacogenetic guided rhythm control intervention trial of bucindolol versus metoprolol succinate for the prevention of recurrent AF or atrial flutter (AFL), included a pre-specified AF burden (AFB) sub-study.MethodsThe AFB cohort included 69 HF patients with reduced (< 0.50) left ventricular ejection fraction (LVEF), symptomatic paroxysmal or persistent AF, ADRB1 Arg389Arg genotype, and continuous rhythm monitoring via insertable cardiac monitor (N=43) or implanted therapeutic devices (N=26) to evaluate AFB. The substudy primary endpoint was time to first event of AFB ≥6 hours per day or death during a 24-week period after establishing sinus rhythm.ResultsPatients had paroxysmal (36%) or persistent (64%) AF and 67% underwent electrical cardioversion prior to the start of efficacy follow-up. Mean LVEF was 0.34 ± 0.08, and 23%, 57%, and 20% had NYHA class I/II/III symptoms at baseline, respectively. For the primary endpoint, the HR was 0.75 (95% CI0.43, 1.32) by the prespecified AFB criteria and 0.69 (95% CI0.38, 1.23) by clinic-based 12-lead ECGs. In the U.S. population (N=42), the HR was 0.49 (95% CI0.24, 1.04) by AFB criteria and 0.41 (95% CI0.19, 0.90) as determined by ECG. The AFB endpoint occurred a median of 6.5 days prior to clinical AF/AFL (p