Roy Denis, Pratt Craig M, Torp-Pedersen Christian, Wyse D George, Toft Egon, Juul-Moller Steen, Nielsen Tonny, Rasmussen S Lind, Stiell Ian G, Coutu Benoit, Ip John H, Pritchett Edward L C, Camm A John
Montreal Heart Institute, University of Montreal, Montreal, Quebec, Canada.
Circulation. 2008 Mar 25;117(12):1518-25. doi: 10.1161/CIRCULATIONAHA.107.723866. Epub 2008 Mar 10.
The present study assessed the efficacy and safety of vernakalant hydrochloride (RSD1235), a novel compound, for the conversion of atrial fibrillation (AF).
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.
Vernakalant demonstrated rapid conversion of short-duration AF and was well tolerated.
本研究评估了新型化合物盐酸维纳卡兰（RSD1235）转复心房颤动（AF）的疗效和安全性。
患者按2:1的比例随机分组，接受维纳卡兰或安慰剂治疗，并根据房颤持续时间分为3小时至7天（短病程）和8至45天（长病程）进行分层。首先给予安慰剂或维纳卡兰（3mg/kg）静脉输注10分钟，如果房颤未终止，15分钟后再给予第二次安慰剂或维纳卡兰（2mg/kg）静脉输注。主要终点是短病程房颤组在开始药物输注90分钟内房颤转复为窦性心律至少1分钟。共有336例患者被随机分组并接受治疗（短病程，n = 220；长病程，n = 116）。在145例接受维纳卡兰治疗的患者中，短病程房颤组有75例（51.7%）转复为窦性心律（中位时间为11分钟），而75例接受安慰剂治疗的患者中有3例（4.0%）转复（P<0.001）。总体而言，在短病程和长病程房颤组中，221例接受维纳卡兰治疗的患者中有83例（37.6%）房颤终止，而115例接受安慰剂治疗的患者中有3例（2.6%）房颤终止（P<0.001）。短暂味觉障碍和打喷嚏是维纳卡兰治疗患者最常见的副作用。3例患者发生了4起与维纳卡兰相关的严重不良事件（低血压[2例]、完全性房室传导阻滞和心源性休克）。
维纳卡兰能快速转复短病程房颤，且耐受性良好。
