Efficacy and safety of vernakalant in patients with atrial flutter: a randomized, double-blind, placebo-controlled trial

TY - JOUR

T1 - Efficacy and safety of vernakalant in patients with atrial flutter

T2 - a randomized, double-blind, placebo-controlled trial

AU - Camm, A John

AU - Toft, Egon

AU - Torp-Pedersen, Christian

AU - Vijayaraman, Pugazhendhi

AU - Juul-Moller, Steen

AU - Ip, John

AU - Beatch, Gregory N

AU - Dickinson, Garth

AU - Wyse, D George

AU - for the Scene 2 Investigators

PY - 2012/6

Y1 - 2012/6

N2 - AimsVernakalant is a novel, relatively atrial-selective antiarrhythmic agent for conversion of atrial fibrillation (AF) to sinus rhythm. This study examined the safety and efficacy of vernakalant in converting atrial flutter (AFL) to sinus rhythm.Methods and resultsThis was a phase 2/3, randomized, double-blind, placebo-controlled trial. Adults with AFL received either a 10 min infusion of 3.0 mg/kg vernakalant (n 39) or placebo (n 15). If AFL or AF persisted at the end of a 15 min observation period, a second 10 min infusion of 2.0 mg/kg vernakalant or placebo was administered. The primary efficacy outcome was the proportion of patients who had treatment-induced conversion of AFL to sinus rhythm for a minimum duration of 1 min within 90 min after the start of the first infusion. No patient in the placebo group met the primary outcome. Only one patient receiving vernakalant (1 of 39, 3) converted to sinus rhythm. A reduced mean absolute ventricular response rate occurred within 50 min in patients receiving vernakalant (mean change from baseline 8.2 b.p.m.) vs. patients receiving placebo (0.2 b.p.m.) (P 0.037). A post-hoc analysis revealed that vernakalant increased AFL cycle length by an average of 55 ms, whereas the AFL cycle length was unchanged in the placebo group (P < 0.001). There was no occurrence of 1: 1 atrio-ventricular conduction. Dysgeusia and sneezing were the most common treatment-related adverse events, consistent with previous reports.ConclusionVernakalant did not restore sinus rhythm in patients with AFL. Vernakalant modestly slowed AFL and ventricular response rates, and was well tolerated.

AB - AimsVernakalant is a novel, relatively atrial-selective antiarrhythmic agent for conversion of atrial fibrillation (AF) to sinus rhythm. This study examined the safety and efficacy of vernakalant in converting atrial flutter (AFL) to sinus rhythm.Methods and resultsThis was a phase 2/3, randomized, double-blind, placebo-controlled trial. Adults with AFL received either a 10 min infusion of 3.0 mg/kg vernakalant (n 39) or placebo (n 15). If AFL or AF persisted at the end of a 15 min observation period, a second 10 min infusion of 2.0 mg/kg vernakalant or placebo was administered. The primary efficacy outcome was the proportion of patients who had treatment-induced conversion of AFL to sinus rhythm for a minimum duration of 1 min within 90 min after the start of the first infusion. No patient in the placebo group met the primary outcome. Only one patient receiving vernakalant (1 of 39, 3) converted to sinus rhythm. A reduced mean absolute ventricular response rate occurred within 50 min in patients receiving vernakalant (mean change from baseline 8.2 b.p.m.) vs. patients receiving placebo (0.2 b.p.m.) (P 0.037). A post-hoc analysis revealed that vernakalant increased AFL cycle length by an average of 55 ms, whereas the AFL cycle length was unchanged in the placebo group (P < 0.001). There was no occurrence of 1: 1 atrio-ventricular conduction. Dysgeusia and sneezing were the most common treatment-related adverse events, consistent with previous reports.ConclusionVernakalant did not restore sinus rhythm in patients with AFL. Vernakalant modestly slowed AFL and ventricular response rates, and was well tolerated.

U2 - 10.1093/europace/eur416

DO - 10.1093/europace/eur416

M3 - Journal article

C2 - 22291438

SN - 1099-5129

VL - 14

SP - 804

EP - 809

JO - Europace

JF - Europace

IS - 6

ER -