Published Online
on March 10, 2008

A more recent version of this article appeared on March 25, 2008

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Submitted on June 28, 2007
Accepted on January 4, 2008

Vernakalant Hydrochloride for Rapid Conversion of Atrial Fibrillation. A Phase 3, Randomized, Placebo-Controlled Trial

Denis Roy MD^*, Craig M. Pratt MD, Christian Torp-Pedersen MD, D. George Wyse MD, PhD, Egon Toft MD, Steen Juul-Moller MD, Tonny Nielsen MD, S. Lind Rasmussen MD, Ian G. Stiell MD, Benoit Coutu MD, John H. Ip MD, Edward L.C. Pritchett MD, A. John Camm MD, for the Atrial Arrhythmia Conversion Trial Investigators

From the Montreal Heart Institute, University of Montreal, Montreal, Quebec, Canada (D.R.); Department of Cardiology, Methodist DeBakey Heart Center, Methodist Hospital Research Institute, Houston, Tex (C.M.P.); Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark (C.T.-P.); Libin Cardiovascular Institute of Alberta, Calgary, Alberta, Canada (D.G.W.); Department for Health Science and Technology, Aalborg University, and Department of Cardiology, Aalborg Hospital, Aalborg, Denmark (E.T.); Universitetssjukhuset I Malmo, Malmo, Sweden (S.J.-M.); Centralsygehuset Esbjerg Varde, Esbjerg, Denmark (T.N.); Hvidovre Hospital, Hvidovre, Denmark (S.L.R.); Department of Emergency Medicine, University of Ottawa, Ottawa, Ontario, Canada (I.G.S.); Notre-Dame Hospital, Montreal, Quebec, Canada (B.C.); Thoracic and Cardiovascular Institute, Lansing, Mich (J.H.I.); Duke University, Durham, NC (E.L.C.P.); and St George's Hospital, London, UK (A.J.C.).

^* To whom correspondence should be addressed. E-mail: d_roy{at}icm-mhi.com.

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 [2 events], complete atrioventricular block, and cardiogenic shock) occurred in 3 patients.

Conclusion—Vernakalant demonstrated rapid conversion of short-duration AF and was well tolerated.

Key words: antiarrhythmia agents • arrhythmia • fibrillation • vernakalant

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