Seneviratne B, Moore G A, West P D
Department of Medicine, Repatriation General Hospital, Greenslopes, Brisbane, Australia.
Br Heart J. 1994 Jul;72(1):63-8. doi: 10.1136/hrt.72.1.63.
To determine the efficacy and dose requirements of captopril to reduce functional mitral regurgitation in patients with dilated heart failure.
A randomised double blind placebo controlled parallel arm trial. Incremental daily doses of 25 mg, 50 mg and 100 mg captopril used for a four week period each for a total of 12 weeks preceded by a two week placebo washout. Twenty eight ambulatory patients (mean age 72) New York Heart Association (NYHA) class II or III with apparently controlled ischaemic dilated heart failure (ejection fraction 29% (0.04%)) on digoxin, diuretics, and nitrates were randomised. All had at least grade 2/4 functional mitral regurgitation (> 5 cm2 regurgitant area on colour flow Doppler).
Twenty three patients completed the study (13 on placebo and 10 on captopril). Significant improvements were confined to the captopril group. Compared with placebo the following improvements were noted in the captopril treated group: mitral regurgitant area decreased from a threshold at 50 mg/day (p < 0.05, mean (95% confidence interval (95% CI)) 3.1 (0.2 to 6.0) cm2), with a further decrease at 100 mg/day (p < 0.01, mean (95% CI) 5.3 (3.1 to 7.5) cm2). Significant improvements in all the other measurements were noted only after 100 mg/day. Stroke volume increased (p < 0.01, mean (95% CI) 11, (1.4 to 21) ml), systemic vascular resistance decreased (p < 0.05, mean (95% CI) 414 (35 to 793) dyn s cm5), left atrial area decreased (p < 0.05, mean (95% CI) 4.3 (0.03 to 8.6) cm2), and deceleration time increased (p < 0.01, mean (95% CI) 52 ms (7 to 98) ms). Left ventricular diameter decreased marginally (p = 0.06, mean (95% CI) 4 (-0.05 to 9 mm). Duke activity index score increased (p < 0.001, median (95% CI) 6.8 (4.5 to 12) points). Heart rate, mean arterial blood pressure, serum creatinine, and serum potassium did not change with either placebo or captopril. No patient was withdrawn directly due to the side effects of captopril. In an open phase nine placebo patients given captopril in rapid increments reaching 100 mg/day in the fourth week showed similar improvements.
Captopril is efficacious in reducing functional mitral regurgitation in dilated heart failure. Patients require and must tolerate high doses (50-100 mg/day) for additive effects over supervised conventional treatment to occur.
确定卡托普利减少扩张型心力衰竭患者功能性二尖瓣反流的疗效及剂量需求。
一项随机双盲安慰剂对照平行组试验。每日递增剂量的25毫克、50毫克和100毫克卡托普利各使用4周，共12周，之前有2周的安慰剂洗脱期。28名门诊患者（平均年龄72岁），纽约心脏病协会（NYHA）心功能II级或III级，患有明显得到控制的缺血性扩张型心力衰竭（射血分数29%（0.04%）），正在服用地高辛、利尿剂和硝酸盐类药物，被随机分组。所有患者至少有2/4级功能性二尖瓣反流（彩色多普勒血流反流面积>5平方厘米）。
23名患者完成了研究（13名服用安慰剂，10名服用卡托普利）。显著改善仅限于卡托普利组。与安慰剂相比，卡托普利治疗组有以下改善：二尖瓣反流面积从50毫克/天的阈值开始下降（p<0.05，平均值（95%置信区间（95%CI））3.1（0.2至6.0）平方厘米），在100毫克/天时进一步下降（p<0.01，平均值（95%CI）5.3（3.1至7.5）平方厘米）。仅在100毫克/天后，所有其他测量指标才有显著改善。每搏输出量增加（p<0.01，平均值（95%CI）11，（1.4至21）毫升），体循环血管阻力下降（p<0.05，平均值（95%CI）414（35至793）达因·秒/平方厘米5），左心房面积下降（p<0.05，平均值（95%CI）4.3（0.03至8.6）平方厘米），减速时间增加（p<0.01，平均值（95%CI）52毫秒（7至98）毫秒）。左心室直径略有下降（p=0.06，平均值（95%CI）4（-0.05至9毫米））。杜克活动指数评分增加（p<0.001，中位数（95%CI）6.8（4.5至12）分）。心率、平均动脉血压、血清肌酐和血清钾在服用安慰剂或卡托普利后均未改变。没有患者因卡托普利的副作用而直接退出研究。在一个开放阶段，9名服用安慰剂的患者迅速递增服用卡托普利，在第四周达到100毫克/天，显示出类似的改善。
卡托普利在减少扩张型心力衰竭患者的功能性二尖瓣反流方面有效。患者需要并必须耐受高剂量（50 - 100毫克/天），才能在有监督的常规治疗基础上产生累加效应。
