Wood M A, Stambler B S, Ellenbogen K A, Gilligan D M, Perry K T, Wakefield L K, VanderLugt J T
Department of Medicine (Cardiology), Medical College of Virginia, Richmond 23298-0053, USA.
Am Heart J. 1998 Jun;135(6 Pt 1):1048-54. doi: 10.1016/s0002-8703(98)70071-7.
Recent studies suggest that class III antiarrhythmic agents may have enhanced efficacy in the treatment of ventricular tachycardia. This study describes the first clinical assessment of the new class III agent ibutilide to suppress inducible monomorphic ventricular tachycardia (VT) in human beings.
Fifty-five patients with coronary artery disease and inducible sustained monomorphic VT at baseline received either low (0.005 mg/kg + 0.001 mg/kg, load and maintenance infusion, respectively), middle (0.01 mg/kg + 0.002 mg/kg), or high dose (0.02 mg/kg + 0.004 mg/kg) infusions of ibutilide followed by repeat programmed ventricular stimulation. The mean age of the study group was 65.5 +/- 9.5 years and mean left ventricular ejection fraction was 36% +/- 11%. Of 48 evaluable patients, 21 (44%) were rendered noninducible after ibutilide, with no difference in efficacy among the three dosing groups (p = 0.83). Ventricular effective refractory periods, QTc interval, and ventricular monophasic action potential duration were prolonged over baseline at all tested cycle lengths. The QTc and action potential prolongation were dose related. Serious drug-related adverse reactions included sustained polymorphic VT in two patients (3.6%), spontaneous monomorphic VT in one patient (1.8%), heart block in one patient (1.8%), and hypotension in one patient (1.8%).
Ibutilide prolongs ventricular repolarization in human beings and demonstrates efficacy in suppressing inducible monomorphic VT. Significant cardiovascular side effects occurred in 12.7% of patients.
近期研究表明,Ⅲ类抗心律失常药物在治疗室性心动过速方面可能具有更高的疗效。本研究描述了新型Ⅲ类药物伊布利特抑制人类可诱导单形性室性心动过速(VT)的首次临床评估。
55例基线时患有冠状动脉疾病且可诱导持续性单形性VT的患者接受了低剂量(负荷量0.005mg/kg,维持输注量0.001mg/kg)、中等剂量(负荷量0.01mg/kg,维持输注量0.002mg/kg)或高剂量(负荷量0.02mg/kg,维持输注量0.004mg/kg)的伊布利特输注,随后进行重复的心室程控刺激。研究组的平均年龄为65.5±9.5岁,平均左心室射血分数为36%±11%。在48例可评估患者中,21例(44%)在使用伊布利特后变为不可诱导,三个剂量组之间的疗效无差异(p = 0.83)。在所有测试的心动周期长度下,心室有效不应期、QTc间期和心室单相动作电位持续时间均较基线延长。QTc和动作电位的延长与剂量相关。严重的药物相关不良反应包括2例患者(3.6%)出现持续性多形性VT、1例患者(1.8%)出现自发性单形性VT、1例患者(1.8%)出现心脏传导阻滞和1例患者(1.8%)出现低血压。
伊布利特可延长人类心室复极,并在抑制可诱导的单形性VT方面显示出疗效。12.7%的患者出现了显著的心血管副作用。