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).


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.


CONCLUSIONS
Vernakalant demonstrated rapid conversion of short-duration AF and was well tolerated.
Roy
Denis
D
Montreal Heart Institute, University of Montreal, Montreal, Quebec, Canada. d_roy@icm-mhi.com
Pratt
Craig M
CM
Torp-Pedersen
Christian
C
Wyse
D George
DG
Toft
Egon
E
Juul-Moller
Steen
S
Nielsen
Tonny
T
Rasmussen
S Lind
SL
Stiell
Ian G
IG
Coutu
Benoit
B
Ip
John H
JH
Pritchett
Edward L C
EL
Camm
A John
AJ
D000368:Aged; D000840:Anisoles / Q000008:administration & dosage* / Q000009:adverse effects; D000889:Anti-Arrhythmia Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000150:complications / Q000188:drug therapy*; D002170:Canada; D004311:Double-Blind Method; D004408:Dysgeusia / Q000139:chemically induced; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010919:Placebos; D011759:Pyrrolidines / Q000008:administration & dosage* / Q000009:adverse effects; D012537:Scandinavian and Nordic Countries; D012912:Sneezing; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States
D000840:Anisoles; D000889:Anti-Arrhythmia Agents; D010919:Placebos; D011759:Pyrrolidines; C524581:vernakalant