Abstract 11520: Safety and Efficacy of Botulinum Toxin Type A for Prevention of Postoperative Atrial Fibrillation in Cardiac Surgery Patients: Pulmonary Function Test Results From the Phase 2 NOVA Study

Abstract

Background: Postoperative atrial fibrillation (POAF) is the most common complication after cardiac surgery. Autonomic neuromodulation, including injection of botulinum toxin into epicardial fat pads, may suppress and/or attenuate atrial fibrillation. The respiratory safety of a potential preventative treatment for AF is critical. Aim: To assess efficacy and pulmonary safety of botulinum toxin type A (BoNT/A; AGN-151607) 125U and 250U vs placebo for prevention of POAF after coronary artery bypass graft and/or valve surgery. Methods: NeurOtoxin for the PreVention of post-operative Atrial fibrillation (NOVA; NCT03779841) was a phase 2, international, multicenter, randomized, placebo-controlled trial. The primary endpoint was proportion of patients with continuous AF ≥30 seconds within the first 30 days. Respiratory function was assessed via pulmonary function tests (PFTs) performed at baseline and day 30 after treatment. Adverse events (AEs), serious adverse events (SAEs), and time to extubation were recorded. Results: A total of 323 patients were randomized: BoNT/A 125U (n=106), 250U (n=109), placebo (n=108). The primary endpoint occurred in 46.1% of the placebo group, 36.5% of the 125U group (relative risk [RR] vs placebo, 0.80 [95% CI: 0.58, 1.10]; P =0.16), and 47.2% of the 250U group (RR vs placebo, 1.04 [95% CI: 0.79, 1.37]; P =0.78). Baseline, day 30, and change from baseline PFT results were similar for active treatment vs placebo ( Table ). Median time to extubation was 9.7, 9.6, and 9.6 h in the placebo, 125U, and 250U groups, respectively. Respiratory AEs were reported in 42.9%, 38.1%, and 50.5% of patients, and respiratory SAEs in 11.4%, 6.7%, and 5.5% of patients in the placebo, 125U, and 250U groups, respectively. Conclusion: In this analysis of respiratory function, there appeared to be no detrimental effect of AGN-151607 compared with placebo, as evidenced by similar outcomes in PFT parameters and respiratory AE/SAE incidences among treatment arms.