Vascular Risk Unit, Department of Internal Medicine, La Paz Hospital, Madrid, Spain.
Clin Ther. 2009 Dec;31(12):2839-50. doi: 10.1016/j.clinthera.2009.12.006.
Aliskiren is approved for the treatment of hypertension at once-daily doses of 150 or 300 mg by the US Food and Drug Administration and the European Commission. It is generally well tolerated and provides 24-hour, dose-dependent blood pressure (BP) reduction; however, the effect of the 75-mg dose has been inconsistent in previous trials.
This study was designed to assess the efficacy and tolerability of once-daily administration of aliskiren 75 mg and to evaluate the dose-response relationship across all 3 doses of aliskiren (75, 150, and 300 mg).
In this 8-week, multicenter, randomized, double-blind, parallel-group, placebo-controlled study, patients aged > or =18 years with stage 1 or 2 essential hypertension entered a 3- to 4-week, single-blind, placebo run-in period. Eligible patients were randomized (1:1:1:1) to receive oral, once-daily doses of aliskiren 75, 150, or 300 mg or placebo. The primary efficacy variable was the change from baseline in mean sitting diastolic BP (msDBP) at the week-8 end point. Tolerability was assessed by monitoring and recording all adverse events (AEs).
A total of 642 patients (mean [SD] age, 52.0 [10.73] years; 60.0% male; 80.8% white; mean body weight, 89.2 [18.4] kg [range, 50-160 kg]) were included in the study. Overall, 576 patients (89.7%) completed the double-blind treatment period. The most frequent reasons for discontinuation were unsatisfactory therapeutic effect (27/642 randomized patients [4.2%]) and AEs (17/642 [2.6%]). At end point, aliskiren 150 and 300 mg significantly reduced msDBP (both, P < 0.001) and mean sitting systolic
This study found a positive linear dose-response relationship in BP reduction with aliskiren 75, 150, and 300 mg dosed once daily, but only aliskiren 150 and 300 mg provided statistically significant reductions from baseline compared with placebo. All 3 doses of aliskiren were generally well tolerated.
阿利吉仑已获美国食品药品监督管理局和欧洲委员会批准，每日一次服用 150 或 300 毫克用于治疗高血压。通常情况下，阿利吉仑具有良好的耐受性，并提供 24 小时、剂量依赖性的血压（BP）降低；然而，在之前的试验中，75 毫克剂量的效果并不一致。
本研究旨在评估每日一次给予阿利吉仑 75 毫克的疗效和耐受性，并评估所有 3 种剂量（75、150 和 300 毫克）的剂量反应关系。
在这项为期 8 周、多中心、随机、双盲、平行组、安慰剂对照研究中，年龄≥18 岁的 1 期或 2 期原发性高血压患者进入 3-4 周的单盲、安慰剂导入期。符合条件的患者以 1:1:1:1 的比例随机（1:1:1:1）接受口服、每日一次的阿利吉仑 75、150 或 300 毫克或安慰剂治疗。主要疗效变量是第 8 周终点时坐位舒张压（msDBP）的基线变化。通过监测和记录所有不良事件（AE）来评估耐受性。
共有 642 名患者（平均[SD]年龄 52.0[10.73]岁；60.0%为男性；80.8%为白人；平均体重 89.2[18.4]kg[范围，50-160kg]）纳入研究。总体而言，576 名患者（89.7%）完成了双盲治疗期。最常见的停药原因是治疗效果不理想（27/642 名随机患者[4.2%]）和不良事件（17/642 [2.6%]）。在终点时，阿利吉仑 150 和 300mg 显著降低 msDBP（均 P<0.001）和坐位收缩压
