Flack John M, Yadao Anthony M, Purkayastha Das, Samuel Rita, White William B
Department of Medicine, Division of Translational Research and Clinical Epidemiology, Wayne State University School of Medicine, Detroit, MI, USA.
J Am Soc Hypertens. 2012 Mar-Apr;6(2):142-51. doi: 10.1016/j.jash.2011.11.004. Epub 2012 Feb 9.
The extent to which the combination of a renin inhibitor with an angiotensin receptor blocker (ARB) lowers clinic and ambulatory blood pressure (BP) versus an ARB alone in stage 2 hypertension is not well known. Hence, we performed an 8-week, randomized, double-blind study in 451 patients with stage 2 hypertension to compare the efficacy of the combination of aliskiren/valsartan 300/320 mg versus valsartan 320 mg. The primary endpoint was change in seated systolic BP from baseline to week 8 analyzed on the intent-to-treat (ITT) population using the last-observation-carried-forward (LOCF) approach; patients completing the entire treatment period (per-protocol completers) were similarly analyzed. For the predefined primary analysis, systolic BP reductions for aliskiren/valsartan (n = 230) and valsartan (n = 217) were -22.1 and -20.5 mm Hg, respectively (P = .295). In per-protocol completers, aliskiren/valsartan (n = 201) lowered BP significantly greater than valsartan (n = 196); -23.7 mm Hg versus -20.3 mm Hg, respectively (P = .028). Although limited by a small sample size (n = 76) using ambulatory BP monitoring, aliskiren/valsartan lowered the 24-hour BP significantly more than valsartan alone (-14.6/-9.0 mm Hg versus -5.9/-4.2 mm Hg; P < .01). Safety and tolerability were similar for the two treatment groups. These data demonstrate the importance of multiple modalities to assess BP changes in clinical trials of antihypertensive therapies, particularly in stage 2 hypertension.
在2期高血压患者中，与单独使用血管紧张素受体阻滞剂（ARB）相比，肾素抑制剂与ARB联合使用降低临床和动态血压（BP）的程度尚不清楚。因此，我们对451例2期高血压患者进行了一项为期8周的随机双盲研究，比较阿利吉仑/缬沙坦300/320 mg与缬沙坦320 mg联合用药的疗效。主要终点是使用末次观察结转（LOCF）方法在意向性治疗（ITT）人群中分析从基线到第8周的坐位收缩压变化；对完成整个治疗期的患者（符合方案完成者）进行了类似分析。对于预定义的主要分析，阿利吉仑/缬沙坦组（n = 230）和缬沙坦组（n = 217）的收缩压降低分别为-22.1和-20.5 mmHg（P = 0.295）。在符合方案完成者中，阿利吉仑/缬沙坦组（n = 201）降低血压的幅度明显大于缬沙坦组（n = 196）；分别为-23.7 mmHg和-20.3 mmHg（P = 0.028）。尽管使用动态血压监测的样本量较小（n = 76）存在局限性，但阿利吉仑/缬沙坦降低24小时血压的幅度明显大于单独使用缬沙坦（-14.6/-9.0 mmHg对-5.9/-4.2 mmHg；P < 0.01）。两个治疗组的安全性和耐受性相似。这些数据表明在抗高血压治疗的临床试验中，尤其是在2期高血压中，采用多种方式评估血压变化的重要性。
