Importance Patients with lower extremity peripheral artery disease (PAD) have reduced lower extremity perfusion, impaired lower extremity skeletal muscle function, and poor walking performance. Telmisartan (an angiotensin receptor blocker) has properties that reverse these abnormalities. Objective To determine whether telmisartan improves 6-minute walk distance, compared with placebo, in patients with lower extremity PAD at 6-month follow-up. Design, Setting, and Participants Double-blind, randomized clinical trial conducted at 2 US sites and involving 114 participants. Enrollment occurred between December 28, 2015, and November 9, 2021. Final follow-up occurred on May 6, 2022. Interventions The trial randomized patients using a 2 × 2 factorial design to compare the effects of telmisartan plus supervised exercise vs telmisartan alone and supervised exercise alone and to compare telmisartan alone vs placebo. Participants with PAD were randomized to 1 of 4 groups: telmisartan plus exercise (n = 30), telmisartan plus attention control (n = 29), placebo plus exercise (n = 28), or placebo plus attention control (n = 27) for 6 months. The originally planned sample size was 240 participants. Due to slower than anticipated enrollment, the primary comparison was changed to the 2 combined telmisartan groups vs the 2 combined placebo groups and the target sample size was changed to 112 participants. Main Outcomes and Measures The primary outcome was the 6-month change in 6-minute walk distance (minimum clinically important difference, 8-20 m). The secondary outcomes were maximal treadmill walking distance; Walking Impairment Questionnaire scores for distance, speed, and stair climbing; and the 36-Item Short-Form Health Survey physical functioning score. The results were adjusted for study site, baseline 6-minute walk distance, randomization to exercise vs attention control, sex, and history of heart failure at baseline. Results Of the 114 randomized patients (mean age, 67.3 [SD, 9.9] years; 46 were women [40.4%]; and 81 were Black individuals [71.1%]), 105 (92%) completed 6-month follow-up. At 6-month follow-up, telmisartan did not significantly improve 6-minute walk distance (from a mean of 341.6 m to 343.0 m; within-group change: 1.32 m) compared with placebo (from a mean of 352.3 m to 364.8 m; within-group change: 12.5 m) and the adjusted between-group difference was -16.8 m (95% CI, -35.9 m to 2.2 m; P = .08). Compared with placebo, telmisartan did not significantly improve any of the 5 secondary outcomes. The most common serious adverse event was hospitalization for PAD (ie, lower extremity revascularization, amputation, or gangrene). Three participants (5.1%) in the telmisartan group and 2 participants (3.6%) in the placebo group were hospitalized for PAD. Conclusions and Relevance Among patients with PAD, telmisartan did not improve 6-minute walk distance at 6-month follow-up compared with placebo. These results do not support telmisartan for improving walking performance in patients with PAD. Trial Registration ClinicalTrials.gov Identifier: NCT02593110.

中文翻译：

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替米沙坦对下肢外周动脉疾病患者步行能力的影响：TELEX 随机临床试验。


重要性 下肢外周动脉疾病（PAD）患者下肢血流灌注减少，下肢骨骼肌功能受损，行走能力差。替米沙坦（一种血管紧张素受体阻滞剂）具有逆转这些异常的特性。目的 确定在 6 个月的随访中，与安慰剂相比，替米沙坦是否能改善下肢 PAD 患者的 6 分钟步行距离。设计、设置和参与者 双盲、随机临床试验在美国 2 个地点进行，涉及 114 名参与者。入组时间为 2015 年 12 月 28 日至 2021 年 11 月 9 日。最终随访时间为 2022 年 5 月 6 日。 干预 该试验使用 2 × 2 析因设计对患者进行随机分组，以比较替米沙坦加监督运动与单独使用替米沙坦和单独进行监督运动，并将单独替米沙坦与安慰剂进行比较。患有 PAD 的参与者被随机分为 4 组中的一组：替米沙坦加运动 (n = 30)、替米沙坦加注意力控制 (n = 29)、安慰剂加运动 (n = 28) 或安慰剂加注意力控制 (n = 27) 6个月。原计划样本量为 240 名参与者。由于入组速度慢于预期，主要比较改为 2 个联合替米沙坦组与 2 个联合安慰剂组，目标样本量改为 112 名参与者。主要结果和措施 主要结果是 6 分钟步行距离的 6 个月变化（最小临床重要差异，8-20 m）。次要结果是最大跑步机步行距离；步行障碍问卷对距离、速度和爬楼梯进行评分；以及 36 项简短健康调查身体机能评分。 结果根据研究地点、基线 6 分钟步行距离、运动与注意力控制的随机分组、性别以及基线心力衰竭病史进行了调整。结果 在 114 名随机患者（平均年龄 67.3 [SD，9.9] 岁；46 名女性 [40.4%]；81 名黑人 [71.1%]）中，105 名（92%）完成了 6 个月的随访。在 6 个月的随访中，与安慰剂相比（从平均 352.3 m 增加到 364.8 m），替米沙坦没有显着改善 6 分钟步行距离（从平均 341.6 m 增加到 343.0 m；组内变化：1.32 m） ；组内变化：12.5 m），调整后的组间差异为 -16.8 m（95% CI，-35.9 m 至 2.2 m；P = .08）。与安慰剂相比，替米沙坦没有显着改善 5 项次要结局中的任何一项。最常见的严重不良事件是因 PAD 住院（即下肢血运重建、截肢或坏疽）。替米沙坦组的 3 名参与者 (5.1%) 和安慰剂组的 2 名参与者 (3.6%) 因 PAD 住院。结论和相关性 在 6 个月的随访中，与安慰剂相比，替米沙坦并未改善 PAD 患者的 6 分钟步行距离。这些结果不支持替米沙坦改善 PAD 患者的步行能力。试验注册 ClinicalTrials.gov 标识符：NCT02593110。