目的：血管紧张素转换酶抑制剂（ACEI）能够减少主要心血管事件，但是有20％的患者不耐受ACEI。因此，本研究评估血管紧张素受体拮抗剂替米沙坦能否用于不能耐受ACEI的心血管疾病或糖尿病终末器官损害的患者。

    方法：在3周的导入期后，5926例患者（多数患者同时接受标准治疗）通过中心自动随机化系统随机接受替米沙坦80mg/天（n＝2954）或安慰剂（n＝2972）治疗。由医院来随机化分层。主要的复合终点是心血管死亡、心肌梗死、脑卒中或因心力衰竭住院治疗。使用意向治疗（ITT）进行分析。

    结果：中位随访期为56月（51～64）。所有患者均被纳入有效性分析。在整个试验过程中，替米沙坦组平均血压较安慰剂组低（两组平均差异为4.0/2.2mmHg[SD 19.6/12.0]）。替米沙坦组中465例 （15.7%）达到主要终点，安慰剂组中504例 （17.0%）达到主要终点（危险比0.92，95％可信区间0.81～1.05，P=0.216）。次要终点为下列之一：心血管死亡、心肌梗死或脑卒中。替米沙坦组中384例（13.0%）达到次要终点，安慰剂组440 例（14.8%)（危险比0.87，95％可信区间0.76～1.00，未调整P=0.048；经过调整与主要终点的重复对比和重叠之后P=0.068）。894例接受替米沙坦治疗的患者（30.3%）因心血管原因住院治疗，而对照组为980例（33.0%）（相对危险0.92，95%可信区间0.85～0.99；P=0.025）。与安慰剂组相比，替米沙坦组中中断治疗的患者更少（替米沙坦组639 [21.6%] vs. 安慰剂组705 [23.8%]；P=0.055）；最常见的中断治疗的原因是低血压症状（替米沙坦组29例[0.98%] vs. 安慰剂组16例[0.54%]）。

    总结：替米沙坦在ACEI不耐受的患者中耐受性良好。虽然这项研究显示替米沙坦对包括心力衰竭住院治疗的主要终点没有显著效果，但是谨慎来说替米沙坦减少了心血管死亡、心肌梗死和脑卒中复合事件的风险。

    编译：陈学颖   上海中山医院

原始摘要：

Background: Angiotensin-converting enzyme (ACE) inhibitors reduce major cardiovascular events， but are not tolerated by about 20% of patients. We therefore assessed whether the angiotensin-receptor blocker telmisartan would be effective in patients intolerant to ACE inhibitors with cardiovascular disease or diabetes with end-organ damage.

Methods: After a 3-week run-in period， 5926 patients， many of whom were receiving concomitant proven therapies， were randomised to receive telmisartan 80 mg/day (n=2954) or placebo (n=2972) by use of a central automated randomisation system. Randomisation was stratified by hospital. The primary outcome was the composite of cardiovascular death， myocardial infarction， stroke， or hospitalisation for heart failure. Analyses were done by intention to treat. This trial is registered with ClinicalTrials.gov， number NCT00153101.

Findings: The median duration of follow-up was 56 (IQR 51–64) months. All randomised patients were included in the efficacy analyses. Mean blood pressure was lower in the telmisartan group than in the placebo group throughout the study (weighted mean difference between groups 4.0/2.2 mm Hg [SD 19.6/12.0]). 465 (15.7%) patients experienced the primary outcome in the telmisartan group compared with 504 (17.0%) in the placebo group (hazard ratio 0.92， 95% CI 0.81–1.05， p=0.216). One of the secondary outcomes—a composite of cardiovascular death， myocardial infarction， or stroke—occurred in 384 (13.0%) patients on telmisartan compared with 440 (14.8%) on placebo (0.87， 0.76–1.00， p=0.048 unadjusted; p=0.068 after adjustment for multiplicity of comparisons and overlap with primary endpoint). 894 (30.3%) patients receiving telmisartan were hospitalised for a cardiovascular reason， compared with 980 (33.0%) on placebo (relative risk 0.92， 95% CI of 0.85–0.99; p=0.025). Fewer patients permanently discontinued study medication in the telmisartan group than in the placebo group (639 [21.6%] vs 705 [23.8%]; p=0.055); the most common reason for permanent discontinuation was hypotensive symptoms (29 [0.98%] in the telmisartan group vs 16 [0.54%] in the placebo group).
 
Interpretation: Telmisartan was well tolerated in patients unable to tolerate ACE inhibitors. Although the drug had no significant effect on the primary outcome of this study， which included hospitalisations for heart failure， it modestly reduced the risk of the composite outcome of cardiovascular death， myocardial infarction， or stroke.