Jordan Jens, Engeli Stefan, Boye Sam W, Le Breton Stephanie, Keefe Deborah L
Franz-Volhard Clinical Research Center, Medical Faculty of the Charité and Helios Klinikum, Berlin, Germany.
Hypertension. 2007 May;49(5):1047-55. doi: 10.1161/HYPERTENSIONAHA.106.084301. Epub 2007 Mar 12.
Current guidelines from the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure recommend first-line treatment with a thiazide diuretic but do not provide specific guidance for obese patients. The renin system is activated in obesity-associated arterial hypertension. Therefore, we tested the hypothesis that the oral direct renin inhibitor aliskiren could provide additive blood pressure lowering in obese patients with hypertension (body mass index >or=30 kg/m(2); mean sitting diastolic blood pressure: 95 to 109 mm Hg) who had not responded to 4 weeks of treatment with hydrochlorothiazide (HCTZ) 25 mg. After a 2- to 4-week washout, 560 patients received single-blind HCTZ (25 mg) for 4 weeks; 489 nonresponders were randomly assigned to double-blind aliskiren (150 mg), irbesartan (150 mg), amlodipine (5 mg), or placebo for 4 weeks added to HCTZ (25 mg), followed by 8 weeks on double the initial doses of aliskiren, irbesartan, or amlodipine. After 8 weeks of double-blind treatment (4 weeks on the higher dose), aliskiren/HCTZ lowered blood pressure by 15.8/11.9 mm Hg, significantly more (P<0.0001) than placebo/HCTZ (8.6/7.9 mm Hg). Aliskiren/HCTZ provided blood pressure reductions similar to those with irbesartan/HCTZ and amlodipine/HCTZ (15.4/11.3 and 13.6/10.3 mm Hg, respectively), with similar tolerability to placebo/HCTZ. Adverse event rates were highest with amlodipine/HCTZ because of a higher incidence of peripheral edema (11.1% versus 0.8% to 1.6% in other groups). In conclusion, combination treatment with aliskiren is a highly effective and well-tolerated therapeutic option for obese patients with hypertension who fail to achieve blood pressure control with first-line thiazide diuretic treatment.
美国国家高血压预防、检测、评估与治疗联合委员会的现行指南推荐噻嗪类利尿剂作为一线治疗药物，但未针对肥胖患者提供具体指导。肾素系统在肥胖相关的动脉高血压中被激活。因此，我们检验了以下假设：对于体重指数≥30kg/m²、静息舒张压均值为95至109mmHg且对25mg氢氯噻嗪（HCTZ）治疗4周无反应的肥胖高血压患者，口服直接肾素抑制剂阿利吉仑可增强降压效果。在2至4周的洗脱期后，560例患者接受单盲HCTZ（25mg）治疗4周；489例无反应者被随机分配至双盲组，分别接受阿利吉仑（150mg）、厄贝沙坦（150mg）、氨氯地平（5mg）或安慰剂治疗4周，同时继续服用HCTZ（25mg），随后8周将阿利吉仑、厄贝沙坦或氨氯地平的初始剂量加倍。双盲治疗8周（高剂量治疗4周）后，阿利吉仑/HCTZ使血压降低15.8/11.9mmHg，显著多于安慰剂/HCTZ（8.6/7.9mmHg，P<0.0001）。阿利吉仑/HCTZ降低血压的幅度与厄贝沙坦/HCTZ和氨氯地平/HCTZ相似（分别为15.4/11.3和13.6/10.3mmHg），且耐受性与安慰剂/HCTZ相似。氨氯地平/HCTZ的不良事件发生率最高，原因是外周水肿的发生率较高（11.1%，而其他组为0.8%至1.6%）。总之，对于一线噻嗪类利尿剂治疗未能控制血压的肥胖高血压患者，阿利吉仑联合治疗是一种高效且耐受性良好的治疗选择。
