{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T08:25:19Z","timestamp":1777451119175,"version":"3.51.4"},"reference-count":101,"publisher":"National Institute for Health and Care Research","issue":"59","license":[{"start":{"date-parts":[[2016,7,1]],"date-time":"2016-07-01T00:00:00Z","timestamp":1467331200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/www.nationalarchives.gov.uk\/doc\/non-commercial-government-licence\/non-commercial-government-licence.htm"}],"funder":[{"DOI":"10.13039\/501100000664","name":"Health Technology Assessment programme","doi-asserted-by":"publisher","award":["08\/109\/02"],"award-info":[{"award-number":["08\/109\/02"]}],"id":[{"id":"10.13039\/501100000664","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NIHR Biomedical Research Centre based at Imperial College NHS Trust"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Health Technol Assess"],"abstract":"<jats:sec id=\"abs1-1\"><jats:title>Background<\/jats:title><jats:p>Although data are inconsistent, angiotensin-converting enzyme inhibitors (ACE-Is) have been associated with a reduced incidence of abdominal aortic aneurysm (AAA) rupture in analysis of administrative databases.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-2\"><jats:title>Objectives<\/jats:title><jats:p>(1) To investigate whether or not the ACE-I perindopril (Coversyl arginine, Servier) reduces small AAA growth rate and (2) to evaluate blood pressure (BP)-independent effects of perindopril on small AAA growth and to compare the repeatability of measurement of internal and external aneurysm diameters.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-3\"><jats:title>Design<\/jats:title><jats:p>A three-arm, multicentre, single-blind, randomised placebo-controlled trial.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-4\"><jats:title>Setting<\/jats:title><jats:p>Fourteen hospitals in England.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-5\"><jats:title>Participants<\/jats:title><jats:p>Men or women aged \u2265\u200955 years with an AAA of 3.0\u20135.4\u2009cm in diameter by internal or external measurement according to ultrasonography and who met the trial eligibility criteria.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-6\"><jats:title>Interventions<\/jats:title><jats:p>Patients were randomised to receive 10\u2009mg of perindopril arginine daily, 5\u2009mg of the calcium channel blocker amlodipine daily or placebo daily.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-7\"><jats:title>Main outcome measures<\/jats:title><jats:p>The primary outcome was AAA diameter growth using external measurements in the longitudinal plane, which in-trial studies suggested was the preferred measure. Secondary outcome measures included AAA rupture, AAA repair, modelling of the time taken for the AAA to reach the threshold for intervention (5.5\u2009cm) or referral for surgery, tolerance of study medication (measured by compliance, adverse events and quality of life) and a comparison of the repeatability of measures of internal and external AAA diameter. Patients were followed up every 3\u20136 months over 2 years.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-8\"><jats:title>Results<\/jats:title><jats:p>In total, 227 patients were recruited and randomised into the three groups, which were generally well matched at baseline. Multilevel modelling was used to determine the maximum likelihood estimates for AAA diameter growth. No significant differences in the estimates of annual growth were apparent [1.68 (standard error 0.02)\u2009mm, 1.77 (0.02)\u2009mm and 1.81 (0.02)\u2009mm in the placebo, perindopril and amlodipine groups, respectively]. Similarly, no significant differences in the slopes of modelled growth over time were apparent between perindopril and placebo (<jats:italic>p<\/jats:italic>\u2009=\u20090.78) or between perindopril and amlodipine (<jats:italic>p<\/jats:italic>\u2009=\u20090.89). The results were essentially unaffected by adjustment for potential confounders. Compliance, measured by pill counts, was good throughout (&gt;\u200980% at all visit time points). There were no significant in-trial safety concerns. Six patients withdrew because of adverse events attributed to the study medications (<jats:italic>n<\/jats:italic>\u2009=\u20092 perindopril,<jats:italic>n<\/jats:italic>\u2009=\u20094 amlodipine). No patients ruptured their AAA and 27 underwent elective surgery during the trial (<jats:italic>n<\/jats:italic>\u2009=\u20099 placebo,<jats:italic>n<\/jats:italic>\u2009=\u200910 perindopril,<jats:italic>n<\/jats:italic>\u2009=\u20098 amlodipine).<\/jats:p><\/jats:sec><jats:sec id=\"abs1-9\"><jats:title>Conclusions<\/jats:title><jats:p>We were unable to demonstrate a significant impact of perindopril compared with placebo or amlodipine on small AAA growth over a 2-year period. Furthermore, there were no differences in the times to reach a diameter of 5.5\u2009cm or undergo surgery among the three groups. Perindopril and amlodipine were well tolerated by this population. External AAA measurements were found to be more repeatable than internal measurements. The observed AAA growth measurement variability was greater than that expected pre trial. This, combined with slower than expected mean growth rates, resulted in our having limited power to detect small differences between growth rates and hence this adds uncertainty to the interpretation of the results. Several further analyses are planned including a multivariate analysis of determinants of AAA growth, an evaluation of the possible differential effect of perindopril on fast AAA growth and an investigation into the roles of central BP and BP variability on AAA growth.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-10\"><jats:title>Trial registration<\/jats:title><jats:p>Current Controlled Trials ISRCTN51383267.<\/jats:p><\/jats:sec><jats:sec id=\"abs1-11\"><jats:title>Funding<\/jats:title><jats:p>This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in<jats:italic>Health Technology Assessment<\/jats:italic>; Vol. 20, No. 59. See the NIHR Journals Library website for further project information. The NIHR Biomedical Research Centre based at Imperial College NHS Trust supported the trial. Servier provided perindopril at no charge.<\/jats:p><\/jats:sec>","DOI":"10.3310\/hta20590","type":"journal-article","created":{"date-parts":[[2016,8,4]],"date-time":"2016-08-04T06:59:53Z","timestamp":1470293993000},"page":"1-180","update-policy":"https:\/\/doi.org\/10.3310\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":25,"title":["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)"],"prefix":"10.3310","volume":"20","clinical-trial-number":[{"clinical-trial-number":"isrctn51383267","registry":"10.18810\/isrctn","type":"results"}],"author":[{"given":"Gaia","family":"Kiru","sequence":"first","affiliation":[{"name":"Imperial Clinical Trials Unit, School of Public Health, Imperial College London, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Colin","family":"Bicknell","sequence":"additional","affiliation":[{"name":"Department of Surgery and Cancer, Imperial College London, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emanuela","family":"Falaschetti","sequence":"additional","affiliation":[{"name":"Imperial Clinical Trials Unit, School of Public Health, Imperial College London, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janet","family":"Powell","sequence":"additional","affiliation":[{"name":"Department of Surgery and Cancer, Imperial College London, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Neil","family":"Poulter","sequence":"additional","affiliation":[{"name":"Imperial Clinical Trials Unit, School of Public Health, Imperial College London, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"on behalf of the AARDVARK collaborators","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"6221","published-online":{"date-parts":[[2016,7]]},"reference":[{"key":"key20160802093000201_ref1-bib1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.ejvs.2010.09.011","article-title":"Management of abdominal aortic aneurysms clinical practice guidelines of the European society for vascular surgery","volume":"41","author":"Moll","year":"2011","journal-title":"Eur J Vasc Endovasc Surg"},{"key":"key20160802093000201_ref1-bib2","volume-title":"Outcomes after Elective Repair of Infra-Renal Abdominal Aortic Aneurysm","author":"Mitchell","year":"2012"},{"key":"key20160802093000201_ref1-bib3","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1016\/j.ejvs.2011.11.014","article-title":"Is the incidence of abdominal aortic aneurysm declining in the 21st century? 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