Ellenbogen K A, Stambler B S, Wood M A, Sager P T, Wesley R C, Meissner M C, Zoble R G, Wakefield L K, Perry K T, Vanderlugt J T
Department of Medicine, Medical College of Virginia, Richmond 23298-0053, USA.
J Am Coll Cardiol. 1996 Jul;28(1):130-6. doi: 10.1016/0735-1097(96)00121-0.
Currently available antiarrhythmic drugs have limited efficacy for short-term, rapid termination of atrial fibrillation and atrial flutter.
Ibutilide fumarate is an investigational class III antiarrhythmic agent that prolongs repolarization by increasing the slow inward sodium current and by blocking the delayed rectifier current. It can be administered intravenously and has a rapid onset of electrophysiologic effects.
The efficacy and safety of ibutilide were studied in 200 patients with atrial flutter > 3 h in duration or atrial fibrillation 3 h to 90 days in duration. Patients were randomized to receive a single intravenous dose of placebo or an infusion of ibutilide fumarate at 0.005, 0.010, 0.015 or 0.025 mg/kg body weight over 10 min. Conversion was defined as termination of the atrial arrhythmia during or within 60 min after infusion. Forty-one patients received placebo and 159 received ibutilide (0.005 mg/kg [n = 41], 0.010 mg/kg [n = 40], 0.015 mg/kg [n = 38] or 0.025 mg/kg [n = 40]).
The arrhythmia terminated in 34% of drug-treated patients. The rates of successful arrhythmia termination were 3% for placebo and 12%, 33%, 45% and 46%, respectively, for 0.005-, 0.010-, 0.015- and 0.025-mg/kg ibutilide. The placebo and 0.005-mg/kg ibutilide groups had lower success rates than all other dose groups (p < 0.05). The mean time to termination of the arrhythmia was 19 min (range 3 to 70) from the start of infusion. Successful arrhythmia termination was not affected by enlarged left atrial diameter, decreased ejection fraction, presence of valvular heart disease or the use of concomitant medications (beta-adrenergic blocking agents, calcium channel blocking agents or digoxin). Arrhythmia termination was not predicted by the magnitude of corrected QT interval prolongation but was associated with a shorter duration of atrial arrhythmia. The most frequent adverse events in ibutilide-treated patients were sustained and nonsustained polymorphic ventricular tachycardia (3.6%). All patients with sustained polymorphic ventricular tachycardia were successfully treated with direct current cardioversion and had no recurrence. The occurrence of proarrhythmia did not correlate with ibutilide plasma concentration.
These data demonstrate that ibutilide is able to rapidly terminate atrial fibrillation and atrial flutter.
目前可用的抗心律失常药物在短期快速终止心房颤动和心房扑动方面疗效有限。
富马酸伊布利特是一种正在研究的III类抗心律失常药物，通过增加缓慢内向钠电流和阻断延迟整流电流来延长复极化。它可以静脉给药，并且电生理作用起效迅速。
在200例心房扑动持续时间>3小时或心房颤动持续时间3小时至90天的患者中研究了伊布利特的疗效和安全性。患者被随机分配接受单次静脉注射安慰剂或在10分钟内以0.005、0.010、0.015或0.025mg/kg体重静脉输注富马酸伊布利特。转复定义为在输注期间或输注后60分钟内终止房性心律失常。41例患者接受安慰剂，159例患者接受伊布利特（0.005mg/kg [n = 41]，0.010mg/kg [n = 40]，0.015mg/kg [n = 38]或0.025mg/kg [n = 40]）。
34%的药物治疗患者心律失常终止。安慰剂组心律失常成功终止率为3%，0.005mg/kg、0.010mg/kg、0.015mg/kg和0.025mg/kg伊布利特组分别为12%、33%、45%和46%。安慰剂组和0.005mg/kg伊布利特组的成功率低于所有其他剂量组（p<0.05）。从输注开始到心律失常终止的平均时间为19分钟（范围3至70分钟）。心律失常的成功终止不受左心房直径增大、射血分数降低、瓣膜性心脏病的存在或同时使用药物（β-肾上腺素能阻滞剂、钙通道阻滞剂或地高辛）的影响。心律失常的终止不能通过校正QT间期延长的幅度来预测，但与房性心律失常的持续时间较短有关。伊布利特治疗患者中最常见的不良事件是持续性和非持续性多形性室性心动过速（3.6%）。所有持续性多形性室性心动过速患者均通过直流电复律成功治疗且无复发。促心律失常的发生与伊布利特血浆浓度无关。
这些数据表明伊布利特能够快速终止心房颤动和心房扑动。
