Chrysant S G
Oklahoma Cardiovascular and Hypertension Center, Oklahoma City, USA.
J Clin Pharmacol. 1997 Jan;37(1):47-52. doi: 10.1177/009127009703700108.
The primary goal of combination therapy is to enhance efficacy without compromising safety. In this multicenter study, the efficacy and tolerability of perindopril added to continuing hydrochlorothiazide therapy were evaluated in patients with mild to moderate (stage I and II), essential hypertension. Two hundred fifty-two patients with supine diastolic blood pressure of 95 mmHg to 114 mmHg were treated for 4 weeks with open-label hydrochlorothiazide at 25 mg/day. The 208 patients whose supine diastolic blood pressure was > or = 90 mmHg at the end of hydrochlorothiazide monotherapy entered a 12-week, double-blind treatment, where placebo or perindopril were added to the 25-mg/ day hydrochlorothiazide therapy as follows: placebo (n = 50) and doses of perindopril at 2 mg/day (n = 52), 4 mg/day (n = 53), and 8 mg/day (n = 53). The perindopril-hydrochlorothiazide combinations decreased both supine systolic blood pressure and supine diastolic blood pressure by 10.3/6.7, 9.6/8.0, and 9.3/6.3 mmHg, for perindopril doses of 2, 4, and 8 mg/day, respectively; there was no difference among the three drug groups. Placebo decreased blood pressure by 1.6/2.0 mmHg, an effect that was significantly lower compared with perindopril-hydrochlorothiazide combinations. Adverse events were mild and similar among all treatment groups, except cough, which was 4.0%, 3.9%, 7.6%, and 13.2% for placebo and perindopril doses of 2, 4, and 8 mg, respectively. The results of this multicenter study indicate that the combination of perindopril and hydrochlorothiazide is safe and effective in lowering blood pressure. The findings also demonstrate that lower doses of perindopril are as effective as higher doses when combined with hydrochlorothiazide.
联合治疗的主要目标是在不影响安全性的前提下提高疗效。在这项多中心研究中，对轻度至中度（I期和II期）原发性高血压患者在继续使用氢氯噻嗪治疗的基础上加用培哚普利的疗效和耐受性进行了评估。252例仰卧位舒张压为95 mmHg至114 mmHg的患者接受了为期4周的开放标签氢氯噻嗪治疗，剂量为25 mg/天。在氢氯噻嗪单药治疗结束时仰卧位舒张压≥90 mmHg的208例患者进入为期12周的双盲治疗阶段，在25 mg/天的氢氯噻嗪治疗基础上加用安慰剂或培哚普利，具体如下：安慰剂组（n = 50）以及培哚普利剂量为2 mg/天（n = 52）、4 mg/天（n = 53）和8 mg/天（n = 53）的组。培哚普利与氢氯噻嗪联合用药时，培哚普利剂量为2、4和8 mg/天，仰卧位收缩压和仰卧位舒张压分别降低10.3/6.7、9.6/8.0和9.3/6.3 mmHg；三个药物组之间无差异。安慰剂使血压降低1.6/2.0 mmHg，与培哚普利-氢氯噻嗪联合用药相比，这一效果显著更低。除咳嗽外，所有治疗组的不良事件均较轻且相似，安慰剂组以及培哚普利剂量为2、4和8 mg时咳嗽的发生率分别为4.0%、3.9%、7.6%和13.2%。这项多中心研究的结果表明，培哚普利与氢氯噻嗪联合用药在降低血压方面安全有效。研究结果还表明，培哚普利与氢氯噻嗪联合使用时，较低剂量与较高剂量同样有效。
