Key result
Perindopril fails to slow small abdominal aortic aneurysm growth compared with placebo.
Why the study?
It was unknown whether ACE-inhibition reduces small abdominal aortic aneurysm growth rate independently of blood pressure lowering.
Does perindopril reduce aneurysm growth rate in adults with small abdominal aortic aneurysms?
RCT (n=224)
Single-blind
1:1:1
Yes
Does perindopril reduce aneurysm growth rate in adults with small abdominal aortic aneurysms?
ACE inhibition with perindopril does not slow the growth of small abdominal aortic aneurysms despite effective blood pressure lowering.
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“The reasons for contrasting results between AAA drug trials and observational findings may simply be the inherent biases introduced in observational designs as well as interactions from effect modifiers, such as degree of optimal blood pressure management, which are difficult to account for. Trials may be underpowered to detect a difference in AAA growth rate, which is slow and prone to interobserver variability”
“At the end of the trial we found that, on average, perindopril was about the same as amlodipine and placebo in terms of affecting AAA growth. However, the AAAs in the trial grew more slowly than expected and the accuracy of ultrasound scanning was less than expected, both of which may have reduced our ability to detect small differences between groups if they were present.”
Perindopril should not be used to slow small AAA growth; challenges observational ACEi associations and reinforces neutral RCT evidence.
AIMS: The AARDVARK (Aortic Aneurysmal Regression of Dilation: Value of ACE-Inhibition on RisK) trial investigated whether ACE-inhibition reduces small abdominal aortic aneurysms (AAA) growth rate, independent of blood pressure (BP) lowering. METHODS AND RESULTS: A three-arm, multi-centre, single-blind, and randomized controlled trial (ISRCTN51383267) was conducted in 14 hospitals in England. Subjects aged ≥55 years with AAA diameter 3.0-5.4 cm were randomized 1:1:1 to receive perindopril arginine 10 mg, or amlodipine 5 mg, or placebo and followed 3-6 monthly over 2 years. The primary outcome was aneurysm growth rate (based on external antero-posterior ultrasound measurements in the longitudinal plane), determined by multi-level modelling to provide maximum likelihood estimates. Two hundred and twenty-four subjects were randomized (2011-2013) to placebo (n = 79), perindopril (n = 73), or amlodipine (n = 72). Mean (SD) changes in mid-trial systolic BP (12 months) were 0.5 (14.3) mmHg, P = 0.78 compared with baseline, -9.5 (13.1) mmHg (P < 0.001), and -6.7 (12.0) mmHg (P < 0.001), respectively. No significant differences in the modelled annual growth rates were apparent [1.68 mm (SE 0.2), 1.77 mm (0.2), and 1.81 mm (0.2), respectively]. The estimated difference in annual growth between the perindopril and placebo groups was 0.08 mm (CI -0.50, 0.65). Similar numbers of AAAs in each group reached 5.5 cm diameter and/or underwent elective surgery: 11 receiving placebo, 10 perindopril, and 11 amlodipine. CONCLUSION: Small AAA growth rates were lower than anticipated, but there was no significant impact of perindopril compared with placebo or placebo and amlodipine, combined despite more effective BP lowering.
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Bicknell et al. (2016) conducted an RCT in Small abdominal aortic aneurysms (n=224). Perindopril arginine vs. Placebo or amlodipine was evaluated on Aneurysm growth rate (MD 0.08, 95% CI -0.50, 0.65, p=0.78). Perindopril did not significantly reduce the annual growth rate of small abdominal aortic aneurysms compared with placebo (difference 0.08 mm, 95% CI -0.50 to 0.65, p=0.78).
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