Waters D, Garceau D
Department of Medicine, Montreal Heart Institute, Quebec, Canada.
J Am Coll Cardiol. 1993 Mar 15;21(4):964-70. doi: 10.1016/0735-1097(93)90354-4.
The efficacy and safety of clentiazem were assessed in 199 patients with stable angina in a dose-ranging, placebo-controlled, double-blind, parallel design study.
To date, this is the first large efficacy and safety study of clentiazem in patients with stable angina.
After washout and a 1-week placebo run-in period, patients received 20, 40, 80 or 120 mg/day of clentiazem tablets or placebo as a twice-daily dosage for 1 week of treatment after 1 week of dose titration. A symptom-limited exercise tolerance test was performed 4 and 12 h after dosing at the end of treatment and results were compared with baseline measurements.
At 4 h after dosing, improvement of exercise duration from baseline value was significantly greater with clentiazem at doses of 40 mg/day (63 +/- 11 s), 80 mg/day (99 +/- 10 s) and 120 mg/day (70 +/- 11 s) than with placebo (34 +/- 10 s). Moreover, clentiazem (80 and 120 mg/day) increased the time to onset of angina and to > or = 1 mm of ST segment depression significantly more than did placebo. At submaximal exercise, clentiazem (40, 80 and 120 mg/day) decreased rate-pressure product, mainly as a result of a decrease in heart rate. At 12 h after dosing, improvement of exercise duration from baseline was significantly greater with clentiazem in doses of 80 mg/day (77 +/- 9 s) and 120 mg/day (70 +/- 10 s) than with placebo (42 +/- 9 s). The incidence of treatment-related adverse events with placebo (27%) and clentiazem (29%) was similar. The most frequently reported treatment-related adverse events with clentiazem were asthenia, headache (both 7.9%), first-degree atrioventricular block and dizziness (both 4.4%).
The results of this short-term study suggest that clentiazem given twice daily in doses of 80 or 120 mg/day is safe and effective monotherapy in the treatment of stable angina.
在一项剂量范围、安慰剂对照、双盲、平行设计研究中，对199例稳定型心绞痛患者评估了克仑硫卓的疗效和安全性。
迄今为止，这是克仑硫卓在稳定型心绞痛患者中的首个大型疗效和安全性研究。
在洗脱期和1周的安慰剂导入期后，患者在剂量滴定1周后，接受20、40、80或120毫克/天的克仑硫卓片或安慰剂，每日两次给药，治疗1周。在治疗结束时给药后4小时和12小时进行症状限制性运动耐量试验，并将结果与基线测量值进行比较。
给药后4小时，40毫克/天（63±11秒）、80毫克/天（99±10秒）和120毫克/天（70±11秒）剂量的克仑硫卓使运动持续时间较基线值的改善显著大于安慰剂（34±10秒）。此外，克仑硫卓（80和120毫克/天）使心绞痛发作时间和ST段压低≥1毫米的时间显著长于安慰剂。在次极量运动时，克仑硫卓（40、80和120毫克/天）降低了心率血压乘积，主要是由于心率降低。给药后12小时，80毫克/天（77±9秒）和120毫克/天（70±10秒）剂量的克仑硫卓使运动持续时间较基线的改善显著大于安慰剂（42±9秒）。安慰剂（27%）和克仑硫卓（29%）的治疗相关不良事件发生率相似。克仑硫卓最常报告的治疗相关不良事件是乏力、头痛（均为7.9%）、一度房室传导阻滞和头晕（均为4.4%）。
这项短期研究的结果表明，每日两次给予80或120毫克/天剂量的克仑硫卓是治疗稳定型心绞痛的安全有效的单一疗法。
