Heart Failure -> Heart Failure Management: -> Pharmacology D-PO06 - Poster Session VI (ID 26) Poster

D-PO06-074 - Impact Of Pharmacogenetic-guided Bucindolol Versus Metoprolol Succinate On The Overall Burden Of Clinical Events In Patients With Atrial Fibrillation And Heart Failure: The Genetic-af Trial (ID 1375)


Background: Bucindolol is a β-blocker/mild vasodilator with the unique pharmacologic properties of sympatholysis and ADRB1 Arg389 inverse agonism. In the GENETIC-AF trial, similar results were observed for bucindolol and metoprolol succinate for the primary endpoint of time to first AF event in HF patients, however, the impact of bucindolol on the overall number of clinical events has not been examined.
Objective: To determine if bucindolol reduces the overall burden of clinical events relative to metoprolol in the GENETIC-AF trial population
Methods: A total of 267 HF patients with recent AF, and the ADRB1 Arg389Arg genotype were randomized (1:1) to study drug and up-titrated to target doses prior to the start of the 24-week follow-up period. Analyses include all patients who entered efficacy follow-up or died at any time (N=259). Incidence rates (IR) were generated for a composite endpoint of AF interventions (i.e., electrical cardioversion, catheter ablation, initiation of Class III antiarrhythmics), cardiovascular adverse events (CV AEs; MedDRA SOC of “Cardiac Disorders”), or death. Comparisons between treatment groups were expressed by the IR Ratio (IRR; IRBUC/IRMET) and tested for significance using the Poisson regression test.
Results: Mean age was 66±10 years, mean left ventricular ejection fraction was 0.36 ± 0.10, and 73% had NYHA II/III symptoms at baseline. Patients had paroxysmal (49%) or persistent (51%) AF, and 44% underwent cardioversion to sinus rhythm prior to follow-up. The composite endpoint was decreased by 28% (IRR= 0.72; 95% CI: 0.54, 0.95; p=0.021) for bucindolol (86 events) compared to metoprolol (115 events). AF interventions comprised the majority of events for both bucindolol (71 events) and metoprolol (88 events). In a subgroup with AF and HF < 12 years who did not have AF >2 years prior to developing HF (N=190), the composite endpoint was reduced by 44% (IRR= 0.56; 95% CI: 0.38, 0.81; p=0.002) for bucindolol (42 events) compared to metoprolol (74 events). Similar results were observed for patients with LVEF values ≥ 0.40.
Conclusion: In a pharmacogenetically-defined HF population at risk for AF recurrence, bucindolol was associated with fewer AF interventions and CV AEs compared to the active control metoprolol succinate.