Department of Internal Medicine, Starnberg Hospital, Academic Teaching Hospital of the Ludwig Maximilian University, Munich, Germany.
Clin Drug Investig. 2004;24(10):593-602. doi: 10.2165/00044011-200424100-00005.
Hypertension guidelines emphasise the need to treat high blood pressure (BP) early and aggressively, giving fixed-dose combinations special consideration. Hitherto, it has not been assessed in a sequential way whether hypertensive patients with inadequately controlled hypertension with an angiotensin II receptor antagonist/hydrochlorothiazide combination benefit from a dose increase of the diuretic. We investigated the efficacy and safety of valsartan 160mg/hydrochlorothiazide 25mg combination in patients with hypertension that was not adequately controlled by valsartan 160mg/hydrochlorothiazide 12.5mg.
This was a multicentre, single-group, prospective study of 646 patients with moderate hypertension (diastolic BP [DBP] 100-109mm Hg). Patients were treated for 4 weeks with valsartan 160mg/hydrochlorothiazide 12.5mg (phase 1: weeks 1-4). In case of non-response (DBP >/=90mm Hg; n = 224) patients were treated for a further 4 weeks with valsartan 160mg/hydrochlorothiazide 25mg (phase 2: weeks 5-8). The primary efficacy measure was a change in mean sitting trough DBP at study end compared with the beginning of phase 2 in the intention-to-treat (ITT) population (n = 221).
Mean age of patients at entry was 58.6 years; 53.7% of patients were female. In phase 1, systolic BP (SBP)/DBP decreased from a baseline value of 161.9/103.3mm Hg by -16.1/-12.4mm Hg (normalisation rate 38.3%, response rate 64.5%). In phase 2, in the ITT non-responder population the additional SBP/DBP decrease was -8.4/-8.3mm Hg. Overall, the normalisation rate in all patients was 55.4% and the responder rate was 76.3%.Tolerability of both the valsartan 160mg/hydrochlorothiazide 12.5mg and the valsartan 160mg/hydrochlorothiazide 25mg combinations was very good, and the switch to the higher dose did not result in an increase in adverse events (AEs) or laboratory abnormalities. Only 16.6% of patients in phase 1 and 10.3% of patients in phase 2 experienced one or more AEs.
In patients with moderate hypertension, first-line therapy with the fixed-dose valsartan/hydrochlorothiazide combination leads to high normalisation and response rates. Patients with hypertension not controlled by valsartan 160mg/ hydrochlorothiazide 12.5mg clearly benefit from dose titration to valsartan 160mg/hydrochlorothiazide 25mg with a clinically relevant additional BP response and have excellent tolerability.
高血压指南强调需要早期积极治疗高血压（BP），特别考虑使用固定剂量联合用药。迄今为止，尚未以连续的方式评估血管紧张素 II 受体拮抗剂/氢氯噻嗪联合用药控制不佳的高血压患者是否受益于增加利尿剂剂量。我们研究了缬沙坦 160mg/氢氯噻嗪 25mg 联合用药在缬沙坦 160mg/氢氯噻嗪 12.5mg 控制不佳的高血压患者中的疗效和安全性。
这是一项多中心、单组、前瞻性研究，纳入 646 例中度高血压（舒张压[DBP]100-109mmHg）患者。患者接受缬沙坦 160mg/氢氯噻嗪 12.5mg 治疗 4 周（第 1 阶段：第 1-4 周）。如果无反应（DBP≥90mmHg；n=224），患者再接受缬沙坦 160mg/氢氯噻嗪 25mg 治疗 4 周（第 2 阶段：第 5-8 周）。主要疗效指标是意向治疗（ITT）人群（n=221）研究结束时与第 2 阶段开始时平均坐位谷 DBP 的变化。
患者入组时的平均年龄为 58.6 岁；53.7%的患者为女性。第 1 阶段，收缩压（SBP）/DBP 从基线值 161.9/103.3mmHg 下降-16.1/-12.4mmHg（正常化率 38.3%，反应率 64.5%）。第 2 阶段，在 ITT 无反应人群中，SBP/DBP 进一步下降-8.4/-8.3mmHg。总体而言，所有患者的正常化率为 55.4%，反应率为 76.3%。两种缬沙坦 160mg/氢氯噻嗪 12.5mg 和缬沙坦 160mg/氢氯噻嗪 25mg 联合用药的耐受性均非常好，增加剂量不会导致不良反应（AE）或实验室异常增加。第 1 阶段仅有 16.6%的患者和第 2 阶段 10.3%的患者出现 1 次或多次 AE。
在中度高血压患者中，一线治疗使用固定剂量缬沙坦/氢氯噻嗪联合用药可实现较高的正常化率和反应率。缬沙坦 160mg/氢氯噻嗪 12.5mg 控制不佳的高血压患者明显受益于剂量滴定至缬沙坦 160mg/氢氯噻嗪 25mg，血压有临床相关的进一步下降，且耐受性极好。
