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Clinical Trial
. 2024 May;10(5):930-940.
doi: 10.1016/j.jacep.2024.01.020. Epub 2024 Apr 24.

Efficacy and Safety of Botulinum Toxin Type A for the Prevention of Postoperative Atrial Fibrillation

Jonathan P Piccini  1 , Anders Ahlsson  2 , Paul Dorian  3 , A Marc Gillinov  4 , Peter R Kowey  5 , Michael J Mack  6 , Carmelo A Milano  7 , Nicolas Noiseux  8 , Louis P Perrault  9 , William Ryan  6 , Jonathan S Steinberg  10 , Pierre Voisine  11 , Nathan H Waldron  12 , Kevin J Gleason  13 , Wilson Titanji  13 , Richard D Leaback  13 , Alexandra O'Sullivan  13 , William G Ferguson  13 , Stefano Benussi  14 ; NOVA-AF Investigators
Collaborators, Affiliations
Free article
Clinical Trial

Efficacy and Safety of Botulinum Toxin Type A for the Prevention of Postoperative Atrial Fibrillation

Jonathan P Piccini et al. JACC Clin Electrophysiol. 2024 May.
Free article

Abstract

Background: Postoperative atrial fibrillation (POAF) is associated with increased morbidity and mortality. Epicardial injection of botulinum toxin may suppress POAF.

Objectives: This study sought to assess the safety and efficacy of AGN-151607 for the prevention of POAF after cardiac surgery.

Methods: This phase 2, randomized, placebo-controlled trial assessed the safety and efficacy of AGN-151607, 125 U and 250 U vs placebo (1:1:1), for the prevention of POAF after cardiac surgery. Randomization was stratified by age (<65, ≥65 years) and type of surgery (nonvalvular/valve surgery). The primary endpoint was the occurrence of continuous AF ≥30 seconds.

Results: Among 312 modified intention-to-treat participants (placebo, n = 102; 125 U, n = 104; and 250 U, n = 106), the mean age was 66.9 ± 6.8 years; 17% were female; and 64% had coronary artery bypass graft (CABG) only, 12% had CABG + valve, and 24% had valve surgery. The primary endpoint occurred in 46.1% of the placebo group, 36.5% of the 125-U group (relative risk [RR] vs placebo: 0.80; 95% CI: 0.58-1.10; P = 0.16), and 47.2% of the 250-U group (RR vs placebo: 1.04; 95% CI: 0.79-1.37; P = 0.78). The primary endpoint was reduced in the 125-U group in those ≥65 years of age (RR: 0.64; 95% CI: 0.43-0.94; P = 0.02) with a greater reduction in CABG-only participants ≥65 years of age (RR: 0.49; 95% CI: 0.27-0.87; P = 0.01). Rehospitalization and rates of adverse events were similar across the 3 groups.

Conclusions: There were no significant differences in the rate of POAF with either dose compared with placebo; however, there was a lower rate of POAF in participants ≥65 years undergoing CABG only and receiving 125 U of AGN-151607. These hypothesis-generating findings require investigation in a larger, adequately powered randomized clinical trial. (Botulinum Toxin Type A [AGN-151607] for the Prevention of Post-operative Atrial Fibrillation in Adult Participants Undergoing Open-chest Cardiac Surgery [NOVA]; NCT03779841); A Phase 2, Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Dose Ranging Study to Evaluate the Efficacy and Safety of Botulinum Toxin Type A [AGN 151607] Injections into the Epicardial Fat Pads to Prevent Post-Operative Atrial Fibrillation in Patients Undergoing Open-Chest Cardiac Surgery; 2017-004399-68).

Keywords: atrial fibrillation; botulinum toxin type A; cardiac surgery; postoperative atrial fibrillation; randomized controlled trial.

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Conflict of interest statement

Funding Support and Author Disclosures AbbVie funded this study (NCT03779841) and participated in the study design, research, analysis, data collection, interpretation of data, reviewing, and approval of the publication. No honoraria or payments were made for authorship. Dr Piccini has received grant support (R01AG074185) from the National Institutes on Aging; has received grants for clinical research from Abbott, American Heart Association, Association for the Advancement of Medical Instrumentation, Bayer, Boston Scientific, iRhythm, and Philips; and has served as a consultant to Abbott, AbbVie, Bayer, Biotronik, Boston Scientific, Bristol Myers Squibb, Element Science, Itamar Medical, LivaNova, Medtronic, Milestone, ElectroPhysiology Frontiers, ReCor, Sanofi, Philips, and Up-to-Date. Dr Ahlsson has received grants for clinical research from the Karolinska Institute. Dr Dorian has received grants for research and honoraria from Milestone Pharma; and has received consulting fees from AbbVie. Dr Gillinov has served as a consultant to AtriCure, Medtronic, Edwards Lifesciences, CryoLife, Abbott, and ClearFlow. Dr Kowey has served as a consultant to AbbVie. Dr Mack has served as co-Principal Investigator or Study Chair for trials for Abbott, Edwards Lifesciences, and Medtronic. Dr Noiseux has received consulting fees from AbbVie. Dr Perrault has served as a consultant for ClearFlow, AbbVie Inc, and Maryzime. Dr Steinberg has received grant support (R34HL126921) from the National Heart, Lung, and Blood Institute; has received research support from AliveCor, Medtronic, National Cardiac, and AtriCure; and has served as a consultant to AbbVie, Medtronic, National Cardiac, AtriCure, Hill-Rom, Cardiolectra, and Corfigo. Dr Voisine has served as a consultant for HLS Therapeutics. Dr Waldron has served as a consultant for AbbVie. Drs Gleason, Titanji, and Leaback, Ms O’Sullivan, and Dr Ferguson are employees of AbbVie and may hold stock options. Dr Benussi has received consulting and/or lecturing fees from AtriCure, CryoLife, and Allergan. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

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