Mercy Health Research, Washington University School of Medicine, St Louis, MO, USA.
Int J Clin Pract. 2010 Sep;64(10):1367-74. doi: 10.1111/j.1742-1241.2010.02480.x.
A majority of hypertensive patients require > or = 2 agents to achieve target blood pressure (BP).
This 52-week, multicentre, open-label, randomised extension trial to a previously reported double-blind, placebo-controlled study evaluated the safety and efficacy of amlodipine/valsartan (Aml/Val) combination. Patients who successfully completed the core study without serious drug-related adverse events (AEs) and mean sitting systolic BP (MSSBP)/mean sitting diastolic BP (MSDBP) < or = 150/95 mmHg were eligible to enter the extension and be treated with Aml/Val 2.5/80 or 5/80 mg. After 4 weeks of treatment, patients underwent force-titration to receive 5/160 mg (low dose) or 10/160 mg (high dose) for 48 weeks. Addition of hydrochlorothiazide (HCTZ) 12.5 mg was permitted if BP was > or = 140/90 mmHg at Week 8 or later. Patients could be down-titrated to the prior lower combination dose with or without HCTZ if an intolerable AE occurred. Safety evaluations included monitoring of AEs. Efficacy variables were change from baseline in MSDBP (primary) and MSSBP (secondary).
Of 1246 patients randomised, 1075 (86.3%) completed the extension study. At week 52 end-point, change in MSSBP/MSDBP from core study baseline was -22.1/-17.2 mmHg for low-dose regimen and -22.8/-18.1 mmHg for high-dose regimen. For both regimens, reductions in BP were sustained over 52 weeks and mean BP maintained below approximately 135/85 mmHg at all visits. Frequent AEs in the low- and high-dose regimens were peripheral oedema (9.7% and 17.1% respectively), nasopharyngitis (8.1% and 7.2%), and dizziness (5.2% and 7.0%). Incidence of serious AEs was 3.7% with low dose and 4.1% with high dose.
The combination of Aml/Val with the optional addition of HCTZ produced clinically significant and persistent reductions in BP over 52 weeks with a favourable tolerability profile.
大多数高血压患者需要使用≥2 种药物才能达到目标血压（BP）。
这是一项对先前报道的双盲、安慰剂对照研究进行的 52 周、多中心、开放性、随机扩展试验，评估了氨氯地平/缬沙坦（Aml/Val）联合用药的安全性和疗效。成功完成核心研究且无严重药物相关不良事件（AE）且平均坐位收缩压（MSSBP）/平均坐位舒张压（MSDBP）＜或＝150/95mmHg 的患者有资格进入扩展期，并接受 Aml/Val 2.5/80 或 5/80mg 治疗。治疗 4 周后，患者进行强制滴定，48 周内接受 5/160mg（低剂量）或 10/160mg（高剂量）治疗。如果第 8 周或之后血压＞或＝140/90mmHg，则允许加用氢氯噻嗪（HCTZ）12.5mg。如果发生无法耐受的 AE，则可将剂量下调至先前的较低联合剂量，且可加用或不加用 HCTZ。安全性评估包括监测 AE。疗效变量为从基线开始的 MSDBP（主要）和 MSSBP（次要）变化。
在 1246 名随机患者中，1075 名（86.3%）完成了扩展研究。在 52 周终点时，低剂量组和高剂量组的 MSSBP/MSDBP 自核心研究基线的变化分别为-22.1/-17.2mmHg 和-22.8/-18.1mmHg。两种方案的血压降低均持续 52 周，且所有就诊时平均血压维持在约 135/85mmHg 以下。低剂量和高剂量方案中常见的 AE 为外周水肿（分别为 9.7%和 17.1%）、鼻咽炎（分别为 8.1%和 7.2%）和头晕（分别为 5.2%和 7.0%）。低剂量组和高剂量组的严重 AE 发生率分别为 3.7%和 4.1%。
Aml/Val 联合用药，可选加用 HCTZ，可在 52 周内显著且持续降低血压，且耐受性良好。
