贝那普利/氨氯地平复方制剂与贝那普利单药治疗轻中度高血压的多中心随机双盲平行对照研究

Comparison of benazepril monotherapy to amlodipine plus benazepril in the treatment of patients with mild and moderate hypertension： a multicentre, randomized, double-blind , parallel-controlled study

目的 评价贝那普利/氨氯地平复方片剂与贝那普利片单药治疗轻、中度高血压患者的有效性和安全性.方法 本研究为多中心、随机、双盲、平行对照研究.356例原发性高血压患者经2周洗脱期后,再给予4周贝那普利片10 mg单药治疗,220例平均坐位舒张压（SeDBP）仍≥90 mm Hg（1 mm Hg=0.133 kPa）的患者随机分为贝那普利（10 mg）/氨氯地平（5 mg）固定剂量复方片剂组（复方制剂组,1片/d,n=113）和贝那普利片单药组（单药治疗组,20 mg/d,n=107）,治疗4周末两组诊室SeDBP≥90 mmHg者剂量加倍.SeDBP＜90 mm Hg者续服原剂量,共随机双盲治疗8周.以总有效率和SeDBP下降差值作为主要疗效指标.其中74例患者（复方片剂组38例,单药组36例）完成了24 h动态血压监测,并作为降压疗效的评价指标.结果 随机、双盲治疗8周末,复方片剂组SeDBP下降值为（11.7±6.8）mm Hg、达目的 血压占65.7%、总有效率为88.5%;单药治疗组SeDBP下降值为（7.7±6.9）mm Hg、达目的 血压占35.5%、总有效率为65.5%.两组组间比较差异均有统计学意义（P＜0.001）.24 h动态血压监测结果,复方制剂组和单药组的舒张压/收缩压（DBP/SBP）的谷/峰比率（T/P）分别为83.1%/76.0%和85.8%/79.5%（P＜0.05）.复方制剂组与单药治疗组的不良反应发生率分别为16.8%和35.5%（P＜0.01）.结论 贝那普利/氨氯地平复方制剂治疗原发性高血压患者的降压疗效明显优于贝那普利单药治疗,且有良好的耐受性.

Objective To evaluate the efficacy and tolerability of the fixed combination of amlodipine 5 mg/benazepril 10 mg once-daily therapy, compared with benazepril, 10 mg, monotherapy in patients with mild and moderate hypertension, and to evaluate the 24 h antihypertensive efficacy and the duration of action by ambulatory blood pressure monitoring Methods In a multicenter, randomized,double-blind, parallel controlled trial, 356 cases of hypertensive patients after 2 weeks wash-out, and then given 4 weeks of benazepril 10 mg monotherapy, 220 patients with mean seated diastolic blood pressure （SeDBP）remained ≥90 mm Hg（1 mm Hg = 0. 133 kPa）were randomly divided into benazepril 10 mg/amlodipine 5 mg（BZ10/AML5）fixed-dose combination therapy group（once a day, n = 113）, and benazepril monotherapy group（daily 20 mg, n = 107）. In the two groups the patients with SeDBP≥90 mm Hg were doubled the dosage of the initial regimen at the end of 4-week treatment for additional 4 weeks , and the patients with SeDBP 〈 90 mm Hg remained the initial regimen for additional 4 weeks. The primary endpoint was to evaluate the improvement of SeDBP at the end of 8-week treatment. There were 74 patients（the combination therapy group n = 38, monotherapy therapy group n = 36）completed the 24 h ambulatory blood pressure monitoring which was included in the final efficacy analysis. Results The randomized, doubleblind treatment for 8 weeks, the mean value of SeDBP reduction, the reaching target blood pressure rate and total successful response rate to the treatment（a SeDBP 〈 90 mm Hg or a decrease of 10 mm Hg or more from baseline）were（11.7 ± 6.8）mm Hg, 65.7% and 88.5% in the combination therapy group,respectively, and were（7.7 ±6. 9）mm Hg, 35.5% and 65.5% in the monotherapy group, respectively.There were statistically significant difference between the combination therapy and the monotherapy groups in all the 3 indexs（P 〈 0. 001）. The fixed combination significantly reduced systolic blood pressure（SBP）and diastolic blood pressure（DBP）values throughout the 24 h. The trough to peak ratios of DBP/SBP in the fixed compound of benazepril/amlodipine（10 mg/5 mg）and benazepril（20 mg）alone were 83. 1%/76. 0% and 85.8%/79. 5%, respectively. Adverse events rates were 16. 8% in the combination therapy group and 35.5% in the monotherapy group（P 〈 0. 001）. Conclusions The combination therapy with benazepril/amlodipine was superior to benazepril monotherapy and was well tolerated in patients with essential hypertension and allowing a satisfactory BP control for 24 hours.