Anderson J L, Askins J C, Gilbert E M, Miller R H, Keefe D L, Somberg J C, Freedman R A, Haft L R, Mason J W, Lessem J N
J Am Coll Cardiol. 1986 Oct;8(4):752-62. doi: 10.1016/s0735-1097(86)80414-4.
Sotalol is a unique beta-adrenergic blocking agent with additional actions characteristic of Vaughn-Williams class III antiarrhythmic agents in experimental models. To test the efficacy of sotalol to suppress ventricular arrhythmias, a 6 week parallel, placebo-controlled out-patient study of two doses (320 and 640 mg/day, in two divided doses) was performed in four hospitals in 56 patients with chronic premature ventricular complexes at a frequency of 30/h or more (mean +/- SE, 528 +/- 60/h) on 48 hour ambulatory electrocardiographic recording. During a placebo week, no change occurred in arrhythmia frequency (532 +/- 76/h). Subsequent sotalol therapy significantly reduced median arrhythmia frequency in patients receiving both low (n = 19) and high (n = 18) doses compared with that in patients receiving placebo (by 77 and 83%, respectively, versus 6%; p less than 0.001). Twenty-two (59%) of 37 sotalol-treated patients, 11 in each group, reached the prospectively defined criterion of efficacy (greater than or equal to 75% arrhythmia reduction) versus 2 (11%) of 19 placebo control patients (p less than 0.001). Sotalol reduced the median frequency of couplets by 94% (p less than 0.0001) and that of runs by 89% (p less than 0.0007). The electrocardiographic effects of sotalol included reductions in heart rate (by 17 to 27%) and increases in the QTc (by 6 to 9%) and PR (by 6%) intervals. Ejection fraction was unchanged. The most common adverse side effect was fatigue, but drug discontinuation was required in only three patients taking 640 mg/day. No proarrhythmic events or biochemical abnormalities were observed. In summary, sotalol displays significant antiarrhythmic activity of moderately high degree with good tolerance in doses of both 320 and 640 mg/day. Its antiarrhythmic actions are distinguished from those reported for other beta-blockers by its effects on the QTc interval and its moderately high degree of antiarrhythmic activity.
索他洛尔是一种独特的β-肾上腺素能阻滞剂，在实验模型中具有其他属于Vaughn-Williams III类抗心律失常药物的特性。为了测试索他洛尔抑制室性心律失常的疗效，在四家医院对56例慢性室性早搏患者进行了一项为期6周的平行、安慰剂对照门诊研究，这些患者的室性早搏频率为每小时30次或更多（平均±标准误，528±60次/小时），采用48小时动态心电图记录。在安慰剂治疗周期间，心律失常频率没有变化（532±76次/小时）。与接受安慰剂的患者相比，随后的索他洛尔治疗显著降低了接受低剂量（n = 19）和高剂量（n = 18）治疗的患者的心律失常中位数频率（分别降低了77%和83%，而安慰剂组为6%；p < 0.001）。在37例接受索他洛尔治疗的患者中，有22例（59%），每组11例，达到了预先定义的疗效标准（心律失常减少≥75%），而19例安慰剂对照患者中有2例（11%）达到该标准（p < 0.001）。索他洛尔使成对早搏的中位数频率降低了94%（p < 0.0001），使连续早搏的中位数频率降低了89%（p < 0.0007）。索他洛尔的心电图效应包括心率降低（17%至27%）、QTc间期延长（6%至9%）和PR间期延长（6%）。射血分数没有变化。最常见的不良反应是疲劳，但仅3例每日服用640 mg的患者需要停药。未观察到促心律失常事件或生化异常。总之，索他洛尔在每日320 mg和640 mg剂量下均显示出显著的中度抗心律失常活性且耐受性良好。其抗心律失常作用通过对QTc间期的影响以及中度高度的抗心律失常活性与其他β受体阻滞剂所报道的作用相区别。
