Queensland Research Centre for Peripheral Vascular Disease, College of Medicine and Dentistry, James Cook University, Townsville, Queensland, Australia.
Department of Surgery, Leiden University Medical Center, Leiden, the Netherlands.
JAMA Cardiol. 2020 Dec 1;5(12):1374-1381. doi: 10.1001/jamacardio.2020.3524.
Currently there is no drug therapy for abdominal aortic aneurysm (AAA).
To test the efficacy of the angiotensin receptor blocker telmisartan in slowing AAA growth in the Telmisartan in the Management of Abdominal Aortic Aneurysm (TEDY) trial.
DESIGN, SETTING, AND PARTICIPANTS: A randomized, double-blind, placebo-controlled trial recruited participants between September 6, 2011, and October 5, 2016, to evaluate the efficacy of telmisartan treatment in patients with AAA. Participants with 35- to 49-mm AAAs recruited from Australia, the Netherlands, and the US were randomized 1:1 to receive telmisartan, 40 mg, or identical placebo. Analyses were conducted according to intention-to-treat principles. Final follow-up was conducted on October 11, 2018, and data analysis was performed between June and November 2019.
Telmisartan, 40 mg, or identical placebo.
The primary outcome of the difference in AAA growth, assessed on core imaging laboratory-read ultrasonographic scanning, was tested with linear mixed-effects models. Other outcomes included effects on blood pressure, computed tomographic (CT)-measured AAA diameter and volume, time to AAA-related events (AAA repair or mortality due to AAA rupture), and health-related quality of life.
Of 300 intended participants, 210 were enrolled and randomized to receive telmisartan (n = 107) or placebo (n = 103). Of patients included in the intention-to-treat analysis (telmisartan: n = 106, placebo: n = 101), 183 were men (88%); mean (SD) age was 73.5 (7.9) years. At 1 year, participants receiving telmisartan had mean lower systolic (8.9; 95% CI, 4.1-13.8 mm Hg; P < .001) and diastolic (7.0; 4.3-9.8 mm Hg; P < .001) blood pressure levels compared with participants receiving placebo. A total of 188 participants (91%) received at least 2 ultrasonographic scans and 133 participants (64%) had at least 2 CT scans. There was no significant difference in ultrasonographic-assessed AAA growth rates among those assigned telmisartan (1.68 mm/y) or placebo (1.78 mm/y): mean difference, -0.11 mm/y (95% CI, -0.60 to 0.38 mm/y; P = .66). Telmisartan had no significant effects on AAA growth assessed by CT-measured AAA diameter (mean difference, -0.01 mm/y; 95% CI, -0.02 to 0.01 mm/y; P = .23) or volume (mean difference, -0.02 cm3/y; 95% CI, -0.04 to 0.00 cm3/y; P = .11), AAA-related events (relative risk, 1.35; 95% CI, 0.54-3.35; P = .52), or health-related quality of life (mean difference in physical component score at 24 months, 0.4; 95% CI, 0.4-0.4; P = .80). Hypotensive symptoms (eg, syncope) were twice as common among participants receiving telmisartan compared with placebo (28 [26%] vs 13 [13%]; P = .02), but overall adverse event rates were otherwise similar for both groups.
This underpowered study did not show a treatment effect for telmisartan on small AAA growth. Future trials will need to ensure adequate sample size and duration of follow-up.
anzctr.org.au Identifier: ACTRN12611000931976; ClinicalTrials.gov Identifier: NCT01683084.
目前尚无治疗腹主动脉瘤（AAA）的药物疗法。
在 Telmisartan 在管理腹主动脉瘤（TEDY）试验中测试血管紧张素受体阻滞剂替米沙坦减缓 AAA 生长的疗效。
设计、地点和参与者：一项随机、双盲、安慰剂对照试验于 2011 年 9 月 6 日至 2016 年 10 月 5 日招募参与者，评估替米沙坦治疗 AAA 患者的疗效。从澳大利亚、荷兰和美国招募的 35-49mm AAA 的参与者被随机分为 1:1 组，分别接受替米沙坦，40mg，或相同的安慰剂。根据意向治疗原则进行分析。最终随访于 2018 年 10 月 11 日进行，数据分析于 2019 年 6 月至 11 月进行。
替米沙坦，40mg，或相同的安慰剂。
核心影像实验室阅读超声扫描评估的 AAA 生长差异的主要结果通过线性混合效应模型进行测试。其他结果包括对血压、CT 测量的 AAA 直径和体积、AAA 相关事件（AAA 修复或 AAA 破裂导致的死亡率）和健康相关生活质量的影响。
在 300 名预期参与者中，有 210 名被纳入并随机接受替米沙坦（n=107）或安慰剂（n=103）治疗。在意向治疗分析中（替米沙坦：n=106，安慰剂：n=101），183 名患者为男性（88%）；平均（SD）年龄为 73.5（7.9）岁。在 1 年时，接受替米沙坦治疗的患者收缩压（8.9；95%CI，4.1-13.8mmHg；P<0.001）和舒张压（7.0；4.3-9.8mmHg；P<0.001）明显低于接受安慰剂的患者。共有 188 名参与者（91%）至少接受了 2 次超声扫描，133 名参与者（64%）至少接受了 2 次 CT 扫描。接受替米沙坦或安慰剂治疗的患者，超声评估的 AAA 生长速度无显著差异（替米沙坦：1.68mm/y；安慰剂：1.78mm/y）：平均差异，-0.11mm/y（95%CI，-0.60 至 0.38mm/y；P=0.66）。替米沙坦对 CT 测量的 AAA 直径（平均差异，-0.01mm/y；95%CI，-0.02 至 0.01mm/y；P=0.23）或体积（平均差异，-0.02cm3/y；95%CI，-0.04 至 0.00cm3/y；P=0.11）、AAA 相关事件（相对风险，1.35；95%CI，0.54-3.35；P=0.52）或健康相关生活质量（24 个月时生理成分评分的平均差异，0.4；95%CI，0.4-0.4；P=0.80）均无显著影响。接受替米沙坦治疗的患者低血压症状（如晕厥）的发生率是安慰剂组的两倍（28[26%]比 13[13%]；P=0.02），但两组的总体不良事件发生率相似。
这项研究效力不足，未显示替米沙坦治疗小型 AAA 生长的疗效。未来的试验将需要确保足够的样本量和随访时间。
anzctr.org.au 标识符：ACTRN12611000931976；ClinicalTrials.gov 标识符：NCT01683084。
