Virginia Commonwealth University Health System, Richmond, USA.
Clin Drug Investig. 2011 Dec 1;31(12):825-37. doi: 10.1007/BF03256921.
Most patients with hypertension will require combination therapy with at least two agents from different antihypertensive classes to achieve blood pressure (BP) control. Thiazide diuretics, such as hydrochlorothiazide (HCTZ), are widely used in combination therapy. The volume reduction with these agents stimulates the renin-angiotensin system (RAS), making RAS inhibitors such as the direct renin inhibitor aliskiren a logical choice for combination therapy with HCTZ.
The aim of this study was to investigate the long-term safety, tolerability and efficacy of the direct renin inhibitor aliskiren, with or without addition of the diuretic HCTZ.
In the 12-month core study, patients with hypertension (mean sitting diastolic BP ≥90 mmHg and <110 mmHg) were randomized in a 3 : 2 ratio to once-daily aliskiren 150 mg or 300 mg. At months 2, 3, 4, 6 and 9, treatment was adjusted in patients not achieving a BP goal of <140/90 mmHg. Patients not at goal on aliskiren 150 mg once daily were up-titrated to aliskiren 300 mg once daily. Patients not at goal with aliskiren 300 mg once daily received add-on HCTZ 12.5 mg once daily, which was up-titrated to 25 mg once daily if BP remained inadequately controlled. At month 12, patients who received aliskiren/HCTZ 300 mg/25 mg once daily for at least 8 months in the core study were eligible to enter a 4-month extension study.
Overall, 1625/1955 patients completed the core study, and 870/1955 patients received add-on HCTZ; 189/198 patients completed the 4-month extension. Aliskiren, with or without add-on HCTZ, was generally well tolerated; the incidence of adverse events (AEs) during the core study was similar among the four final treatment groups. The most frequently reported AEs in the core and extension studies were mild and transient cases of nasopharyngitis, headache and dizziness. Few patients exhibited laboratory abnormalities. Overall, aliskiren, with or without add-on HCTZ, reduced mean BP by 18.0/12.7 mmHg at core study endpoint, and 61.2% of patients achieved BP control. BP reductions with aliskiren/HCTZ 300 mg/25 mg combination therapy at the core study endpoint were maintained during the extension study.
In patients with hypertension, long-term treatment with aliskiren, with or without add-on HCTZ, is well tolerated and provides effective BP lowering that is sustained over 12 months.
大多数高血压患者需要联合使用至少两种来自不同降压类别的药物来控制血压。噻嗪类利尿剂，如氢氯噻嗪（HCTZ），广泛用于联合治疗。这些药物的体积减少会刺激肾素-血管紧张素系统（RAS），这使得直接肾素抑制剂阿利克仑成为与 HCTZ 联合治疗的合理选择。
本研究旨在探讨直接肾素抑制剂阿利克仑长期使用的安全性、耐受性和疗效，无论是否联合使用利尿剂 HCTZ。
在为期 12 个月的核心研究中，高血压患者（平均坐位舒张压≥90mmHg 且<110mmHg）以 3:2 的比例随机分为每日一次阿利克仑 150mg 或 300mg 组。在第 2、3、4、6 和 9 个月时，如果血压未达到<140/90mmHg 的目标，则调整治疗。不能达到每日一次阿利克仑 150mg 目标血压的患者，将剂量增加至每日一次 300mg。每日一次阿利克仑 300mg 仍未达标的患者，加用氢氯噻嗪 12.5mg 每日一次，如果血压仍未得到充分控制，则将剂量增加至 25mg 每日一次。在核心研究的第 12 个月，至少在核心研究中接受阿利克仑/氢氯噻嗪 300mg/25mg 每日一次治疗 8 个月的患者有资格进入为期 4 个月的扩展研究。
共有 1625/1955 名患者完成了核心研究，870/1955 名患者接受了加用氢氯噻嗪；189/198 名患者完成了 4 个月的扩展研究。阿利克仑，无论是否加用氢氯噻嗪，通常都具有良好的耐受性；在四个最终治疗组中，核心研究期间不良反应（AE）的发生率相似。核心和扩展研究中最常报告的 AE 为轻度和短暂的鼻咽炎、头痛和头晕。少数患者出现实验室异常。总体而言，阿利克仑，无论是否加用氢氯噻嗪，在核心研究终点时平均降低血压 18.0/12.7mmHg，61.2%的患者达到血压控制目标。在核心研究期间，阿利克仑/氢氯噻嗪 300mg/25mg 联合治疗在核心研究终点时的降压作用在扩展研究中得以维持。
在高血压患者中，长期使用阿利克仑，无论是否加用氢氯噻嗪，均具有良好的耐受性，并能有效降低血压，且持续 12 个月。
