Comparative effectiveness and safety of vernakalant, flecainide, and amiodarone for atrial fibrillation cardioversion: a propensity score–matched analysis

Abstract Background Vernakalant is approved in Europe, Canada, and several Asian countries for the pharmacological cardioversion of recent-onset atrial fibrillation (AF), but remains unauthorized in the United States due to FDA safety concerns. Its role in emergency department (ED) management of AF requires further comparative evaluation against other agents. Methods We conducted a retrospective observational study including all AF episodes treated with intravenous (iv) vernakalant, flecainide, or amiodarone in a single ED between January 2012 and December 2022. Clinical data were extracted from patient records. The primary outcome was sinus rhythm (SR) conversion during the ED stay. Secondary outcomes included time to SR, ED length of stay, AF recurrence, ED revisits, and rehospitalizations within 6 months, as well as adverse events (AEs) occurring during drug infusion or during the ED stay. Inverse probability of treatment weighting (IPTW) was applied to adjust for baseline confounding. Subgroup analyses explored the impact of demographic and clinical variables on treatment response and safety. Results We analyzed 899 AF episodes (vernakalant: 262; flecainide: 151; amiodarone: 486). SR conversion rates were 76.7% (vernakalant), 69.5% (flecainide), and 67.3% (amiodarone). Median time to SR was significantly shorter with vernakalant (0.25 h), compared to flecainide (2.58 h) and amiodarone (8 h; p < 0.001). Vernakalant was associated with shorter ED stays. During follow-up, ED revisits and rehospitalizations occurred less frequently in vernakalant-treated patients than in amiodarone-treated patients, although these findings should be interpreted cautiously given baseline differences between groups. AEs occurred in 15.3% (vernakalant), 16.6% (flecainide), and 12.6% (amiodarone); flecainide showed a higher incidence of AEs of special interest. In patients with NYHA class I–II heart failure, vernakalant showed increased efficacy but also higher AE rates. Conclusions Vernakalant showed comparable overall efficacy to amiodarone and flecainide for cardioversion of recent-onset AF, with faster SR conversion and shorter ED stays. However, given the retrospective design, non-random treatment allocation, and baseline differences between groups, these comparative findings should be interpreted with caution. Vernakalant may be a useful option in selected patients when rapid cardioversion is desired.