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A genotype-directed comparative effectiveness trial of Bucindolol and metoprolol succinate for prevention of symptomatic atrial fibrillation/atrial flutter in patients with heart failure: Rationale and design of the GENETIC-AF trial

Few therapies are available for the safe and effective treatment of atrial fibrillation (AF) in patients with heart failure. Bucindolol is a non-selective beta-blocker with mild vasodilator activity previously found to have accentuated antiarrhythmic effects and increased efficacy for preventing hea...

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Published in:The American heart journal 2018-05, Vol.199, p.51-58
Main Authors: Piccini, Jonathan P., Connolly, Stuart J., Abraham, William T., Healey, Jeff S., Steinberg, Benjamin A., Al-Khalidi, Hussein R., Dignacco, Patricia, van Veldhuisen, Dirk J., Sauer, William H., White, Michel, Wilton, Stephen B., Anand, Inder S., Dufton, Christopher, Marshall, Debra A., Aleong, Ryan G., Davis, Gordon W., Clark, Richard L., Emery, Laura L., Bristow, Michael R.
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cited_by cdi_FETCH-LOGICAL-c353t-dfe92f38a9b255accff87e3e2bc2c92f9722c1a9186aa9a6b0c598897adc803c3
cites cdi_FETCH-LOGICAL-c353t-dfe92f38a9b255accff87e3e2bc2c92f9722c1a9186aa9a6b0c598897adc803c3
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container_issue
container_start_page 51
container_title The American heart journal
container_volume 199
creator Piccini, Jonathan P.
Connolly, Stuart J.
Abraham, William T.
Healey, Jeff S.
Steinberg, Benjamin A.
Al-Khalidi, Hussein R.
Dignacco, Patricia
van Veldhuisen, Dirk J.
Sauer, William H.
White, Michel
Wilton, Stephen B.
Anand, Inder S.
Dufton, Christopher
Marshall, Debra A.
Aleong, Ryan G.
Davis, Gordon W.
Clark, Richard L.
Emery, Laura L.
Bristow, Michael R.
description Few therapies are available for the safe and effective treatment of atrial fibrillation (AF) in patients with heart failure. Bucindolol is a non-selective beta-blocker with mild vasodilator activity previously found to have accentuated antiarrhythmic effects and increased efficacy for preventing heart failure events in patients homozygous for the major allele of the ADRB1 Arg389Gly polymorphism (ADRB1 Arg389Arg genotype). The safety and efficacy of bucindolol for the prevention of AF or atrial flutter (AFL) in these patients has not been proven in randomized trials. The Genotype-Directed Comparative Effectiveness Trial of Bucindolol and Metoprolol Succinate for Prevention of Symptomatic Atrial Fibrillation/Atrial Flutter in Patients with Heart Failure (GENETIC-AF) trial is a multicenter, randomized, double-blinded “seamless” phase 2B/3 trial of bucindolol hydrochloride versus metoprolol succinate, for the prevention of symptomatic AF/AFL in patients with reduced ejection fraction heart failure (HFrEF). Patients with pre-existing HFrEF and recent history of symptomatic AF are eligible for enrollment and genotype screening, and if they are ADRB1 Arg389Arg, eligible for randomization. A total of approximately 200 patients will comprise the phase 2B component and if pre-trial assumptions are met, 620 patients will be randomized at approximately 135 sites to form the Phase 3 population. The primary endpoint is the time to recurrence of symptomatic AF/AFL or mortality over a 24-week follow-up period, and the trial will continue until 330 primary endpoints have occurred. GENETIC-AF is the first randomized trial of pharmacogenetic guided rhythm control, and will test the safety and efficacy of bucindolol compared with metoprolol succinate for the prevention of recurrent symptomatic AF/AFL in patients with HFrEF and an ADRB1 Arg389Arg genotype. (ClinicalTrials.govNCT01970501).
doi_str_mv 10.1016/j.ahj.2017.12.001
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title A genotype-directed comparative effectiveness trial of Bucindolol and metoprolol succinate for prevention of symptomatic atrial fibrillation/atrial flutter in patients with heart failure: Rationale and design of the GENETIC-AF trial
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