An evaluation of the effect of an angiotensin-converting enzyme inhibitor on the growth rate of small abdominal aortic aneurysms: A randomised placebo controlled trial (AARDVARK)
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Published version
Author(s)
Type
Journal Article
Abstract
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.
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.
Date Issued
2016-11-07
Date Acceptance
2016-05-31
Citation
European Heart Journal, 2016, 37 (42), pp.3213-3221
ISSN
1522-9645
Publisher
Oxford University Press (OUP)
Start Page
3213
End Page
3221
Journal / Book Title
European Heart Journal
Volume
37
Issue
42
Copyright Statement
& The Author 2016. Published by Oxford University Press on behalf of the European Society of Cardiology.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which
permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact
journals.permissions@oup.com
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which
permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact
journals.permissions@oup.com
Sponsor
National Institute for Health Research
Imperial College Healthcare NHS Trust- BRC Funding
Grant Number
08/109/02
RDC02 79560
Subjects
Science & Technology
Life Sciences & Biomedicine
Cardiac & Cardiovascular Systems
Cardiovascular System & Cardiology
Abdominal aortic aneurysm
ACE-inhibition
Perindopril
Blood pressure lowering
Calcium channel blocker
Placebo-controlled
BLOOD-PRESSURE
DOSE-RESPONSE
MORTALITY
HYPERTENSION
PERINDOPRIL
REPAIR
ACE-inhibition
Abdominal aortic aneurysm
Blood pressure lowering
Calcium channel blocker
Perindopril
Placebo-controlled
Angiotensin-Converting Enzyme Inhibitors
Antihypertensive Agents
Aortic Aneurysm, Abdominal
Blood Pressure
Double-Blind Method
England
Humans
Hypertension
Likelihood Functions
Middle Aged
Single-Blind Method
AARDVARK Collaborators
Humans
Aortic Aneurysm, Abdominal
Hypertension
Antihypertensive Agents
Angiotensin-Converting Enzyme Inhibitors
Likelihood Functions
Double-Blind Method
Single-Blind Method
Blood Pressure
Middle Aged
England
Cardiovascular System & Hematology
1102 Cardiorespiratory Medicine and Haematology
1103 Clinical Sciences
Publication Status
Published
Date Publish Online
2016-07-01