Laurent Stéphane
Service de Pharmacologie, INSERM EMI 107, Hôpital Européen Georges Pompidou, 20 rue Leblanc, 75015 Paris, France.
J Hypertens Suppl. 2003 Jun;21(3):S11-8. doi: 10.1097/00004872-200306003-00003.
To review the safety and efficacy of the very-low-dose combination of perindopril 2 mg and indapamide 0.625 mg (Per2/Ind0.625) in essential hypertension, in relation to blood pressure control and target-organ damage.
We included in this review several double-blind, randomized studies in hypertensive patients, including five main studies from the European registration file and two clinical trials on regression of target-organ damage [large artery stiffness: the Preterax in Regression of Arterial Stiffness in a Controlled Double-Blind Study (REASON); microalbuminuria in patients with type 2 diabetes: the Preterax in Albuminuria Regression (PREMIER) study].
Systolic (SBP) and diastolic (DBP) blood pressures measured at trough with a mercury sphygmomanometer, an automatic device (OMRON), and 24-h ambulatory blood pressure measurements (ABPM). Arterial stiffness, assessed from pulse wave velocity measurement and augmentation index (REASON study). Microalbuminuria (PREMIER study).
The Per2/Ind0.625 combination was selected from the dose-finding studies. Twelve weeks after the participants were assigned to study groups, the reductions in SBP, measured with an OMRON device, were 12.3 +/- 15.0 mmHg with Per2/Ind0.625, 8.0 +/- 16.5 mmHg with perindopril 2 mg (P = 0.001), 9.4 +/- 14.3 mmHg with indapamide 0.625 mg (P = 0.023) and 2.1 +/- 16.8 mmHg with placebo (P < 0.001) (mean +/- SD; all P values are for comparisons with Per2/Ind0.625). The reductions in DBP were 6.8 +/- 9.2 mmHg, 5.0 +/- 9.5 mmHg (P = 0.02), 4.7 +/- 8.2 mmHg (P = 0.004) and 2.4 +/- 9.6 mmHg (P < 0.001) in the Per2/Ind0.625, perindopril 2 mg, indapamide 0.625 mg and placebo groups, respectively. During the long-term study, among 235 patients who achieved initial blood pressure normalization with the fixed combination, 79.8% sustained their normalized status over 1 year, with no significant difference regarding safety criteria. During the REASON study, Per/Ind reduced pulse wave velocity to a similar extent as atenolol, and augmentation index to a greater extent. During the PREMIER study, Per/Ind reduced microalbuminuria to a greater extent than did enalapril.
The proven efficacy on blood pressure and regression of target-organ damage with a good safety profile confirm that the new fixed-low-dose combination Per2/Ind0.625 is a valuable option in the first-line treatment of hypertension.
回顾培哚普利2毫克与吲达帕胺0.625毫克的极低剂量组合（Per2/Ind0.625）在原发性高血压治疗中的安全性和有效性，以及其对血压控制和靶器官损害的影响。
本综述纳入了多项针对高血压患者的双盲、随机研究，包括欧洲注册档案中的五项主要研究以及两项关于靶器官损害逆转的临床试验[大动脉僵硬度：培哚普利在动脉僵硬度逆转的对照双盲研究（REASON）；2型糖尿病患者的微量白蛋白尿：培哚普利在白蛋白尿逆转（PREMIER）研究]。
使用汞柱式血压计、自动设备（欧姆龙）在谷值时测量的收缩压（SBP）和舒张压（DBP），以及24小时动态血压监测（ABPM）。通过脉搏波速度测量和增强指数评估动脉僵硬度（REASON研究）。微量白蛋白尿（PREMIER研究）。
Per2/Ind0.625组合是从剂量探索研究中筛选出来的。参与者被分配到研究组12周后，使用欧姆龙设备测量的SBP降低值分别为：Per2/Ind0.625组为12.3±15.0毫米汞柱，培哚普利2毫克组为8.0±16.5毫米汞柱（P = 0.001），吲达帕胺0.625毫克组为9.4±14.3毫米汞柱（P = 0.023），安慰剂组为2.1±16.8毫米汞柱（P < 0.001）（均值±标准差；所有P值均为与Per2/Ind0.625组比较）。DBP降低值在Per2/Ind0.625组、培哚普利2毫克组、吲达帕胺0.625毫克组和安慰剂组分别为6.8±9.2毫米汞柱、5.0±9.5毫米汞柱（P = 0.02）、4.7±8.2毫米汞柱（P = 0.004）和2.4±9.6毫米汞柱（P < 0.001）。在长期研究中，235例使用固定组合实现初始血压正常化的患者中，79.8%在1年以上维持了正常状态，在安全性标准方面无显著差异。在REASON研究中，培哚普利/吲达帕胺降低脉搏波速度的程度与阿替洛尔相似，但降低增强指数的程度更大。在PREMIER研究中，培哚普利/吲达帕胺降低微量白蛋白尿的程度比依那普利更大。
在血压控制和靶器官损害逆转方面已证实的疗效以及良好的安全性表明，新的固定低剂量组合Per2/Ind0.625是高血压一线治疗中有价值的选择。
