Waeber Bernard
Division of Clinical Pathophysiology, University Hospital, Lausanne, Switzerland.
J Hypertens Suppl. 2006 May;24(3):S19-27. doi: 10.1097/01.hjh.0000229465.09610.b6.
Pharmacological treatment of hypertension represents a cost-effective way of preventing cardiovascular and renal complications. To benefit maximally from antihypertensive treatment, blood pressure should be brought to below 140/90 mmHg in every hypertensive patient, and even lower (< 130/80 mmHg) if diabetes or renal disease co-exists. Such targets cannot usually be reached using monotherapies. This is especially true in patients who present with a high cardiovascular risk. The co-administration of two agents acting by different mechanisms considerably increases the blood pressure control rate. Such combinations are not only efficacious, but are also well tolerated, and some fixed low-dose combinations even have a placebo-like tolerability. This is the case for the preparation containing the angiotensin-converting enzyme inhibitor perindopril (2 mg) and the diuretic indapamide (0.625 mg), a fixed low-dose combination that has been shown in controlled trials to be more effective than monotherapies in reducing albuminuria, regressing cardiac hypertrophy and improving the stiffness of large arteries. Using this combination to initiate antihypertensive therapy has been shown in a double-blind trial (Strategies of Treatment in Hypertension: Evaluation; STRATHE) to normalize blood pressure (< 140/90 mmHg) in significantly more patients (62%) than a sequential monotherapy approach based on atenolol, losartan and amlodipine (49%) and a stepped-care strategy based on valsartan and hydrochlorothiazide (47%), with no difference between the three arm groups in terms of tolerability. An ongoing randomized trial (Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation; ADVANCE) is a study with a 2 x 2 factorial design assessing the effects of the fixed-dose perindopril-indapamide combination and of the intensive gliclazide modified release-based glucose control regimen in type 2 diabetic patients, with or without hypertension. A total of 11 140 patients were randomly selected. Within the first 6 weeks of treatment (run-in phase), the perindopril-indapamide combination lowered blood pressure from 145/81 +/- 22/11 mmHg (mean +/- SD) to 137/78 +/- 20/10 mmHg. Fixed-dose combinations are becoming more and more popular for the management of hypertension, and are even proposed by hypertension guidelines as a first-line option to treat hypertensive patients.
高血压的药物治疗是预防心血管和肾脏并发症的一种经济有效的方法。为了从降压治疗中获得最大益处，每位高血压患者的血压应降至140/90 mmHg以下；若同时患有糖尿病或肾脏疾病，则血压应降至更低水平（<130/80 mmHg）。通常单一疗法无法达到这些目标。对于心血管风险较高的患者尤其如此。联合使用两种作用机制不同的药物可显著提高血压控制率。这种联合不仅有效，而且耐受性良好，一些固定低剂量复方制剂甚至具有类似安慰剂的耐受性。含有血管紧张素转换酶抑制剂培哚普利（2 mg）和利尿剂吲达帕胺（0.625 mg）的制剂就是如此，这一固定低剂量复方制剂在对照试验中已显示出在降低蛋白尿、使心脏肥大消退以及改善大动脉僵硬度方面比单一疗法更有效。在一项双盲试验（高血压治疗策略：评估；STRATHE）中，与基于阿替洛尔、氯沙坦和氨氯地平的序贯单一疗法（49%）以及基于缬沙坦和氢氯噻嗪的阶梯式治疗策略（47%）相比，使用这种联合疗法起始降压治疗能使更多患者（62%）的血压恢复正常（<140/90 mmHg），三组在耐受性方面无差异。一项正在进行的随机试验（糖尿病和血管疾病行动：培哚普利吲达帕胺复方制剂与达美康缓释片对照评估；ADVANCE）是一项采用2×2析因设计的研究，评估固定剂量培哚普利 - 吲达帕胺复方制剂以及强化的基于格列齐特缓释片的血糖控制方案对伴有或不伴有高血压的2型糖尿病患者的影响。总共随机选取了11140名患者。在治疗的前6周（导入期），培哚普利 - 吲达帕胺复方制剂使血压从145/81±22/11 mmHg（均值±标准差）降至137/78±20/10 mmHg。固定剂量复方制剂在高血压管理中越来越受欢迎，甚至被高血压指南推荐为治疗高血压患者的一线选择。
