Genetically Targeted Therapy for the Prevention of Symptomatic Atrial Fibrillation in Patients With Heart Failure

The goal of the GENETIC-AF trial is to demonstrate the superiority of pharmacogenetically
targeted bucindolol compared to metoprolol for the prevention of symptomatic atrial
fibrillation or atrial flutter in a genotype-defined population with heart failure and/or
reduced left ventricular ejection fraction at high risk of atrial fibrillation/atrial flutter
recurrence.

Key Inclusion Criteria:

- Must weigh at least 40 kg

- Possess the β1389 Arg/Arg genotype

- Left Ventricular Ejection Fraction (LVEF) < 0.50 assessed within 12 months prior to
Screening

- At least one episode of symptomatic paroxysmal or persistent AF within 180 days of
Screening

- Clinically appropriate for electrical cardioversion (ECV) if AF/AFL is present after
study drug initiation

- Receiving appropriate anticoagulation therapy prior to Randomization

Key Exclusion Criteria:

- NYHA Class IV symptoms at the time of Randomization

- Significant fluid overload at Randomization

- Permanent AF at Screening

- More than two previous ECV within 6 months of Randomization or if the most recent ECV
failed to produce SR

- Presence of an LVAD, or likely to requirement LVAD placement within 6 months of
Randomization

- History of a successful atrioventricular (AV) node ablation

- History of an AF/AFL ablation within 30 days of Randomization

- Evidence of an appropriate firing of an implanted cardioverter-defibrillator (ICD)
device for ventricular tachycardia (VT) or ventricular fibrillation (VF) within 90
days of Randomization