Vernakalant for cardioversion of recent-onset atrial fibrillation: a systematic review and meta-analysis

Aims To evaluate the efficacy and safety of vernakalant for the cardioversion of atrial fibrillation (AF). Methods and results We reviewed the literature for randomized trials that compared vernakalant to another drug or placebo in patients with AF of onset <= 7 days. We used a random-effects model to combine quantitative data and rated the quality of evidence using the GRADE (Grades of Recommendation, Assessment, Development and Evaluation). From 441 total citations in MEDLINE, EMBASE, and CENTRAL (December 2018), we identified nine trials evaluating 1358 participants. Six trials compared vernakalant to placebo, two trials compared vernakalant to ibutilide, and one trial compared vernakalant to amiodarone. We found significant methodological bias in four trials. For conversion within 90 min, vernakalant was superior to placebo [50% conversion, risk ratio (RR) 5.15; 95% confidence interval (CI); 2.24-11.84, I-2 = 91%], whereas we found no significant difference in conversion when vernakalant was compared with an active drug (56% vs. 24% conversion, RR 2.40; 95% CI 0.76-7.58, I-2 = 94). Sinus rhythm was maintained at 24 h in 85% (95% CI 80-88%) of patients who converted acutely with vernakalant. Overall, we judged the quality of evidence for efficacy to be low based on inconsistency and suspected publication bias. There was no significant difference in the risk of significant adverse events between vernakalant and comparator (RR 0.95; 95% CI 0.70-1.28, I-2 = 0, moderate quality evidence). Vernakalant is safe and effective for rapid and durable restoration of sinus rhythm in patients with recent-onset AF. Conclusion Vernakalant should be a first line option for the pharmacological cardioversion of patients with haemodynamically stable recent-onset AF without severe structural heart disease.