Epicardial botulinum toxin injection for now does not lower burden of postoperative AF
Temporary Neurotoxin Treatment to Prevent Postoperative Atrial Fibrillation
Presented at AHA 2017 Scientific Sessions in Anaheim, CA, USA by Nathan Waldron (Duke University Medical Center, Durham, NC, USANews - Nov. 20, 2017
- No significant difference was seen in the risk of POAF between patients receiving epicardial botulinum toxin and placebo (HR: 0.69- 95%CI: 0.40-1.18, P=0.18).
- Adjusted analyses accounting for preoperative risk factors for POAF and ACEi usage, did not show significant difference in the primary outcome either (HR: 0.70, 95%CI: 0.41-1.21, P=0.21).
- Secondary efficacy outcomes showed a significantly shorter duration of first episode of POAF in patients receiving epicardial botulinum toxin (1.9 hours vs. 5.5 hours, P=0.01), a non-significantly numerically lower POAF incidence (23% vs. 32%, P=0.19).
- No significant differences were seen in total POAF duration (15.4 hours vs. 17.3 hours, P=0.70), overall POAF burden (8.2% vs. 8.7%, P=0.83), treatment of POAF (amiodarone: 87% vs. 94%, P=0.64, electrical cardioversion 9% vs. 19%, P=0.30), or LOS (ICU: 25.7 vs. 23.1 hours, P=0.16, post-surgery LOS (6.0 vs. 6.2 days, P=0.51).
- No significant difference was seen between groups in the primary safety outcome of duration of postoperative intubation (6.0 vs. 6.8 hours, P=0.06), nor in the incidence of any adverse events (AEs, 69.8% vs. 70.1%, P=0.97) or any serious AEs (42.9% vs. 44.8%, P=0.83).
- No significant differences were seen in the incidence of serious AEs that prolong LOS.
This study shows that patients receiving epicardial botulinum toxin injection had a numerically lower risk of POAF that did not reach statistical significance, along with a shorter duration of first POAF episode without resultant changes in burden or treatment of POAF. From a safety standpoint, no significant differences were detected in duration of postoperative mechanical ventilation, length of stay, or postoperative adverse events.
It should be noted that this study included a heterogeneous group of high-risk patients, undergoing multiple types of surgery. Based on the findings of the pilot study, this study was powered (80%) to detect 40% reduction, thus it was underpowered to detect smaller, but clinically significant reductions in POAF. The current study differed from the pilot study in that the latter enrolled patients with a known history of pAF, only undergoing CABG, and the current population was at higher risk, given the inclusion of valvular procedures and the higher mean age and prevalence of COPD. Also some procedural aspects were different.
Overall, Waldron concluded that these findings warrant further study in larger trials, to further evaluate the potential protective ability of this strategy.
Discussant Renate B. Schnabel agreed that we are in need of a means to temporary block autonomic activation to prevent POAF. Botulinum toxin injection has been shown to be effective in a small study, both immediately post-operatively and in longer-term follow-up. She notes that the current study was quite optimistically powered to detect 40% reduction.
Critical points include that only 6.4% of patients screened were considered eligible, which may have induced bias. For instance, patients with LVEF <25% were excluded, which represents a common group of patients who undergo cardiac surgery. The fact that prior AF was permitted may have diluted the effect. At present, she thinks that this study does not help us to understand the transient nature of POAF. It does, however, give insight into the role of autonomic imbalance, particularly parasympathetic activation in POAF. She appreciates this innovative way of possibly reducing POAF burden, and anticipates more explosive results in the future.
- Our reporting is based on the information provided at the AHA 2017 congress -