Efficacy of Telmisartan to Slow Growth of Small Abdominal Aortic Aneurysms: A Randomized Clinical Trial

Abstract

Importance: Currently there is no drug therapy for abdominal aortic aneurysm (AAA).

Objective: 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.

Intervention: Telmisartan, 40 mg, or identical placebo.

Main outcomes and measures: 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.

Results: 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.

Conclusions and relevance: 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.

Trial registrations: anzctr.org.au Identifier: ACTRN12611000931976; ClinicalTrials.gov Identifier: NCT01683084.

Conflict of interest statement

Conflict of Interest Disclosures: Prof Golledge reported receiving personal fees from Amgen & Reven, having shares in the stock market, and receiving grants from Townsville Hospital and James Cook University outside the submitted work. Dr Dalman reported receiving grants from Medtronic Inc outside the submitted work. Dr Morris reported receiving grants from General Sir John Monash Scholarship Avant Doctor in Training Research Scholarship during the conduct of the study. No other disclosures were reported.

Figures

Figure 1.. Flow of Included Participants

Numbers of patients assessed for eligibility, randomized, follow-up events (cumulative), and participants having ultrasonographic and computed tomographic (CT) imaging of their abdominal aortic aneurysm (AAA). ACE indicates angiotensin converting enzyme; ARB, angiotensin receptor blocker. aThe 6156 exclusions are enumerated in the Results section. bThree patients withdrawn after randomization owing to ineligibility, complete withdrawal, and duplicate randomization.

Figure 2.. Effect of Telmisartan Compared With Placebo on Blood Pressure

Blood pressure among patients randomized to receive telmisartan vs placebo for systolic (A) or diastolic (B) blood pressure (8.9; 95% CI, 4.1-13.8 mm Hg vs 7.0; 4.3-9.8 mm Hg). Summary mean differences reported at 1 year (trial midpoint). Error bars represent 95% CI.

Figure 3.. Effect of Telmisartan on Small Abdominal Aortic Aneurysm (AAA) Growth Measured Using Ultrasonographic Imaging

Core imaging laboratory-read AAA diameter measured as the maximum infrarenal outer-to-outer aortic diameter in the anteroposterior plane for telmisartan (1.68 mm/y; 95% CI, 1.33-2.02 mm/y) and placebo (1.78 mm/y; 95% CI, 1.44-2.13 mm/y). Mean difference, −0.11 (95% CI, −0.60 to 0.38 mm/y). Error bars represent 95% CI.

Figure 4.. Effect of Telmisartan on Small Abdominal Aortic Aneurysm (AAA) Growth Measured Using Computed Tomographic (CT) Imaging

AAA diameter and volume measured in a central core laboratory. Measurements recorded for 186 participants at baseline, 102 participants at 1 year, and 121 participants at 2 years. Error bars represent 95% CI.