血管紧张素II受体拮抗剂替米沙坦治疗单纯收缩期高血压（ARAMIS）研究：20毫克、40毫克或80毫克替米沙坦与12.5毫克氢氯噻嗪或安慰剂的疗效及安全性比较

Angiotensin II receptor antagonist telmisartan in isolated systolic hypertension (ARAMIS) study: efficacy and safety of telmisartan 20, 40 or 80 mg versus hydrochlorothiazide 12.5 mg or placebo.

作者信息

Manolis Athanasios J, Reid John L, de Zeeuw Dick, Murphy Michael B, Seewaldt-Becker Elke, Köster Jürgen

机构信息

Txanio General Hospital, Piraeus, Greece.

出版信息

J Hypertens. 2004 May;22(5):1033-7. doi: 10.1097/00004872-200405000-00027.

DOI:10.1097/00004872-200405000-00027

PMID:15097245

Abstract

OBJECTIVE

To identify telmisartan doses that are more effective than placebo and non-inferior to hydrochlorothiazide (HCTZ) 12.5 mg, and are well tolerated, in lowering systolic blood pressure (SBP) in patients with isolated systolic hypertension (ISH).

PATIENTS AND METHODS

A 2-4-week single-blind placebo run-in was followed by randomization of 1039 patients (age 36-84 years) with ISH [seated SBP 150-179 mmHg and seated diastolic blood pressure (DBP) < 90 mmHg] to once-daily double-blind treatment with telmisartan 20, 40 or 80 mg, HCTZ 12.5 mg, or placebo. The change in seated trough SBP after 6 weeks compared with baseline was the primary end point. Secondary end points were the percentage achieving the target fall in SBP and the change from baseline in seated trough DBP. Incidence and severity of adverse events and physical examination and laboratory parameters were monitored for the safety evaluation.

RESULTS

Baseline demographics in telmisartan 20 mg (n = 206), 40 mg (n = 210), 80 mg (n = 207), HCTZ 12.5 mg (n = 205) and placebo (n = 211) treatment groups were comparable: (mean +/- SD) age, 63.0 +/- 10.9 years; SBP, 162.9 +/- 8.1 mmHg; and DBP 83.4 +/- 5.0 mmHg. No previous antihypertensive therapy had been received by 66% of the patients. Mean reductions in seated trough SBP (adjusted for baseline and country) were: telmisartan 20 mg, 15.6 mmHg (n = 204); 40 mg, 17.9 mmHg (n = 209); and 80 mg, 16.9 mmHg (n = 205), compared with placebo, 11.4 mmHg (n = 208), and HCTZ 12.5 mg, 15.7 mmHg (n = 204). The target fall in seated trough SBP (< or =140 mmHg or reduction by > or =20 mmHg) was achieved in 46.6% (telmisartan 20 mg), 51.7% (telmisartan 40 mg), 53.9% (telmisartan 80 mg), 27.4% (placebo) and 42.7% (HCTZ 12.5 mg); the response rate was significantly higher for telmisartan 80 mg than for HCTZ 12.5 mg (P = 0.03). All-causality adverse events occurred in 19.9, 17.6 and 20.3% receiving telmisartan 20, 40 and 80 mg, respectively; 20.9% receiving placebo and 22.0% receiving HCTZ 12.5 mg. No drug-related serious adverse events occurred.

CONCLUSIONS

All doses of telmisartan (20-80 mg) were significantly superior to placebo in reducing SBP in patients with ISH and clinically comparable to HCTZ 12.5 mg. Tolerability of telmisartan was similar to that of placebo.

摘要

目的

确定在降低单纯收缩期高血压（ISH）患者收缩压（SBP）方面比安慰剂更有效且不劣于12.5 mg氢氯噻嗪（HCTZ）、耐受性良好的替米沙坦剂量。

患者和方法

1039例ISH患者（年龄36 - 84岁，坐位SBP 150 - 179 mmHg且坐位舒张压（DBP）< 90 mmHg）先进行2 - 4周单盲安慰剂导入期，然后随机分为每日一次接受20、40或80 mg替米沙坦、12.5 mg HCTZ或安慰剂的双盲治疗。6周时坐位谷值SBP相对于基线的变化为主要终点。次要终点为达到SBP目标降幅的百分比以及坐位谷值DBP相对于基线的变化。监测不良事件的发生率和严重程度以及体格检查和实验室参数以进行安全性评估。

结果

替米沙坦20 mg（n = 206）、40 mg（n = 210）、80 mg（n = 207）、HCTZ 12.5 mg（n = 205）和安慰剂（n = 211）治疗组的基线人口统计学特征具有可比性：（均值±标准差）年龄63.0±10.9岁；SBP 162.9±8.1 mmHg；DBP 83.4±5.0 mmHg。66%的患者此前未接受过抗高血压治疗。坐位谷值SBP的平均降低值（根据基线和国家进行调整）为：替米沙坦20 mg组降低15.6 mmHg（n = 204）；40 mg组降低17.9 mmHg（n = 209）；80 mg组降低16.9 mmHg（n = 205），而安慰剂组降低11.4 mmHg（n = 208），HCTZ 12.5 mg组降低了15.7 mmHg（n = 204）。坐位谷值SBP达到目标降幅（≤140 mmHg或降低≥20 mmHg）的比例在替米沙坦20 mg组为46.6%，40 mg组为51.7%，80 mg组为53.9%，安慰剂组为27.4%，HCTZ 12.5 mg组为42.7%；替米沙坦80 mg组的反应率显著高于HCTZ 组12.5 mg（P = 0.03）。接受20、40和80 mg替米沙坦治疗的患者中，全因性不良事件的发生率分别为19.9%、17.6%和20.3%；接受安慰剂治疗的为20.9%，接受12.5 mg HCTZ治疗的为22.0%。未发生与药物相关的严重不良事件。