Vernakalant versus procainamide for rapid cardioversion of patients with acute atrial fibrillation (RAFF4): randomised clinical trial

Abstract Objective To conduct a randomised, open label comparison of the effectiveness and safety of intravenous vernakalant and intravenous procainamide for the management of acute atrial fibrillation in the emergency department. Design Randomised clinical trial (RAFF4 trial). Setting 12 tertiary care emergency departments in Canada. Participants Patients with acute atrial fibrillation for whom acute rhythm control was a safe option. Interventions Patients were randomised (1:1) to an intravenous infusion of vernakalant or procainamide; when rapid conversion did not occur, patients were offered electrical cardioversion. Main outcomes and measures The primary outcome was conversion to sinus rhythm within 30 minutes of drug infusion completion. Secondary outcomes included time to conversion to sinus rhythm and whether the patient required electrical cardioversion. Results Of the 350 enrolled eligible patients, baseline characteristics were similar in the procainamide (n=172) and vernakalant (n=178) groups. For the primary outcome of conversion success, vernakalant was more effective (62.4% v 48.3%; adjusted absolute difference 15.0%, 95% confidence interval 4.6% to 25.0%, P=0.005; adjusted odds ratio 1.87, 95% confidence interval 1.2 to 2.9, P=0.006). With vernakalant, time to conversion was faster (21.8 v 44.7 minutes; mean difference −22.9, 95% confidence interval −29.9 to −16.0, P<0.001), and fewer patients underwent attempted electrical cardioversion (33.7% v 44.2%; odds ratio 0.62, 95% confidence interval 0.39 to 0.96, P=0.033). Adverse events were similar in both groups, were generally mild and brief, and most patients were discharged home. Subgroup analysis strongly favoured vernakalant for conversion in patients younger than 70 years (73.3% v 47.2%; adjusted odds ratio 3.1, 95% confidence interval 1.7 to 5.5, P=0.001, interaction P=0.005). Conclusions In this head-to-head comparison, vernakalant was superior to procainamide for patients with higher conversion rates and faster times to conversion. Therefore, vernakalant is a safe and highly effective intravenous alternative for the rapid cardioversion and discharge home of patients with acute atrial fibrillation. Trial registration ClinicalTrials.gov NCT04485195