D-PO01-040 - Pharmacogenomic Guided Beta-blocker Therapy Withbucindolol Reduces Atrial Fibrillation Burden Compared To Metoprolol Succinate: The Genetic-af Trial (ID 892)
Background: Bucindolol is a genetically-targeted β-blocker/mild vasodilator with sympatholysis and ADRB1 Arg389 inverse agonism.
Objective: Analyze AF burden by treatment arm in patients with AF & HF in the GENETIC-AF device substudy.
Methods: In the device substudy, 69 AF/HF patients with the ADRB1 Arg389Arg genotype were randomized to study drug and up-titrated to target dosesprior to the start of efficacy follow-up. Cumulative time in AF was measured by implanted devices capable of assessing AF burden on all patients entering efficacy follow-up (N=68). The mean number of days in AF was expressed as an incidence rate (IR; hours in AF divided by 24 hours and total patients). 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 0.35 ± 0.09 and 76% had NYHA II/III symptoms at baseline. Patients had paroxysmal (37%) or persistent (63%) AF, and 59% underwent cardioversion to sinus rhythm prior to the start of efficacy follow-up. Patients in the bucindolol group had a mean of 38.7 days in AF during the 24-week efficacy follow-up period compared to 52.3 days in the metoprolol group (26% reduction; IRR=0.74; 95% CI: 0.69, 0.79; p < 0.001). In a subgroup with AF and HF <12 years who did not have AF >2 years prior to developing HF (N=49), a 37% reduction was observed with bucindolol versus metoprolol (IRR=0.63; 95% CI: 0.58, 0.69; p < 0.001).
Conclusion: In a pharmacogenetically-defined HF population at risk for AF recurrence, bucindolol significantly decreased the cumulative AF burden compared to the active control metoprolol succinate.