Genetic AF

A Genotype-Directed Comparative Effectiveness Trial of Bucindolol and Toprol-XL for Prevention of Symptomatic Atrial Fibrillation/Atrial Flutter in Patients With Heart Failure

Genetic AF [NCT01970501]

Description: This study is being done to compare the effects of bucindolol hydrochloride (bucindolol) to metoprolol succinate (Toprol-XL) on the recurrence of symptomatic atrial fibrillation/atrial flutter in patients with heart failure who have a specific genotype for the beta-1 adrenergic receptor.

Drug: bucindolol hydrochloride; Drug: metoprolol succinate

Primary Investigator: Egnaczyk

Drug/Device Information
To compare the effects of bucindolol and metoprolol on the recurrence of symptomatic AF/AFL in patients with HFREF who have a ß1389 arginine homozygous (ß1389Arg/Arg) genotype
Bucindolol hydrochloride (bucindolol) is a nonselective ß-adrenergic receptor (AR) blocking agent with mild vasodilator properties
Metoprolol succinate (Toprol-XL) is a ß1-AR selective ß-blocker
Randomized (1:1) to blinded treatment with bucindolol or metoprolol
Up-titrated weekly to target doses of 50 mg BID (< 75 kg) or 100 mg BID (≥ 75 kg) for bucindolol or 200 mg QD for metoprolol
ARCA biopharma, Inc.
Major Inclusion and Exclusion
Age ≥ 18 years and ≤ 85
Possess the ß1389Arg/Arg genotype
History of heart failure with reduced left ventricle ejection fraction (HFREF), LVEF < 0.50
At least one symptomatic paroxysmal or persistent AF episode ≤ 180 days
Clinically appropriate for ECV if AF/AFL is present at the week 0 visit
Receiving guideline indicated oral anticoagulation therapy at the randomization visit, which is considered optimal for stroke prevention in the opinion of the investigator
No significant fluid overload at the randomization visit
No permanent AF
No amiodarone, disopyramide, dofetilide, dronedarone, flecainide, propafenone, sotalol, nondihydropyridine calcium channel blockers, daily NSAIDS, thiazolidinediones
No frequent use of short acting nitroglycerin
No successful atrioventricular node ablation
No moderate to severe asthma or other obstructive lung disease requiring chronic use (> 2 days/week) of an inhaled ß2-selective adrenergic agonist
No renal failure requiring dialysis, serum creatinine > 2.5 mg/dL or an estimated creatinine clearance < 30 mL/min