Vernakalant hydrochloride for rapid conversion of atrial fibrillation - A phase 3, randomized, placebo-controlled trial

Background - The present study assessed the efficacy and safety of vernakalant hydrochloride ( RSD1235), a novel compound, for the conversion of atrial fibrillation ( AF). Methods and Results - Patients were randomized in a 2: 1 ratio to receive vernakalant or placebo and were stratified by AF duration of 3 hours to 7 days ( short duration) and 8 to 45 days ( long duration). A first infusion of placebo or vernakalant ( 3 mg/kg) was given for 10 minutes, followed by a second infusion of placebo or vernakalant ( 2 mg/kg) 15 minutes later if AF was not terminated. The primary end point was conversion of AF to sinus rhythm for at least 1 minute within 90 minutes of the start of drug infusion in the short-duration AF group. A total of 336 patients were randomized and received treatment (short duration, n = 220; long duration, n = 116). Of the 145 vernakalant patients, 75 (51.7%) in the short-duration AF group converted to sinus rhythm ( median time, 11 minutes) compared with 3 of the 75 placebo patients ( 4.0%; P < 0.001). Overall, in the short-and long-duration AF groups, 83 of the 221 vernakalant patients (37.6%) experienced termination of AF compared with 3 of the 115 placebo patients ( 2.6%; P < 0.001). Transient dysgeusia and sneezing were the most common side effects in vernakalant-treated patients. Four vernakalant-related serious adverse events (hypotension [ events], complete atrioventricular block, and cardiogenic shock) occurred in 3 patients. Conclusion - Vernakalant demonstrated rapid conversion of short-duration AF and was well tolerated.