An analysis of drug modulation of abdominal aortic aneurysm growth through 25 years of surveillance

Thompson, Andrew R.; Cooper, Jackie A.; Fabricius, Michael; Humphries, Steve E.; Ashton, H. A.; Hafez, Hany

doi:10.1016/j.jvs.2010.02.012

Cited by 135 publications

(112 citation statements)

References 22 publications

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“…The Chichester small AAA surveillance study suggested an association between ARB prescription and reduced AAA progression. 71 However, in contrast, a report from the UK Small Aneurysm Study group reported a small but significant association between ACE-I prescription and increased AAA expansion. 72 This significant difference remained after adjustment for known confounders such as smoking, diabetes, BP and peripheral atherosclerosis.…”

Section: Angiotensin-converting Enzyme Inhibitionmentioning

confidence: 94%

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)

Kiru

Bicknell

Falaschetti

et al. 2016

Health Technol Assess

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BACKGROUND: 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. OBJECTIVES: (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. DESIGN: A three-arm, multicentre, single-blind, randomised placebo-controlled trial. SETTING: Fourteen hospitals in England. PARTICIPANTS: Men or women aged ≥ 55 years with an AAA of 3.0-5.4 cm in diameter by internal or external measurement according to ultrasonography and who met the trial eligibility criteria. INTERVENTIONS: Patients were randomised to receive 10 mg of perindopril arginine daily, 5 mg of the calcium channel blocker amlodipine daily or placebo daily. MAIN OUTCOME MEASURES: 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 cm) 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 3-6 months over 2 years. RESULTS: 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) mm, 1.77 (0.02) mm and 1.81 (0.02) mm 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 (p = 0.78) or between perindopril and amlodipine (p = 0.89). The results were essentially unaffected by adjustment for potential confounders. Compliance, measured by pill counts, was good throughout (> 80% 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 (n = 2 perindopril, n = 4 amlodipine). No patients ruptured their AAA and 27 underwent elective surgery during the trial (n = 9 placebo, n = 10 perindopril, n = 8 amlodipine). CONCLUSIONS: 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 cm or undergo surgery among the three groups. Perindopril and amlodipine were well tolerated by this population. ...

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Section: Angiotensin-converting Enzyme Inhibitionmentioning

confidence: 94%

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)

Kiru

Bicknell

Falaschetti

et al. 2016

Health Technol Assess

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“…A previous ultrasound surveillance study involving 1269 patients with abdominal aortic aneurysm found that the prescription of potassium sparing diuretics (presumed to be mainly the MR antagonist spironolactone) was associated with a reduced rate of aneurysm expansion, although this association was lost after adjusting for other medications. 10 Hyperaldosteronism has also been associated with cerebral aneurysm formation in patients. 11 Based on the above data it is tempting to conclude that aldosterone is the primary effector of angiotensin II in stimulating aortic aneurysm and dissection in mice models and thus a possible target for drug therapy.…”

Section: See Accompanying Article On Page 1568mentioning

confidence: 99%

mentioning

confidence: 99%

Is There a New Target in the Renin–Angiotensin System for Aortic Aneurysm Therapy?

Golledge

2013

ATVB

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A ortic aneurysm and aortic dissection are important causes of mortality, which are principally managed by surgical interventions.1-3 The absence of specific medications which can limit the complications of these important aortic pathologies has stimulated an intense interest in studying the mechanisms underlying these diseases.1-3 A major focus of these studies has been the renin-angiotensin system. Angiotensin II has been linked to aortic aneurysm and dissection on the basis of evidence from a range of studies. In >100 studies in specific mice species (eg, apolipoprotein E-deficient mice), it has been shown that angiotensin II infusion stimulates aortic aneurysm and dissection formation and rupture.1 Such angiotensin II-induced aneurysms have some features typically found in human abdominal aortic aneurysms, including upregulation of proinflammatory cytokines and matrix metalloproteinases and marked influx of inflammatory cells. 4 The concentration of a variety of angiotensin II-producing enzymes, including angiotensin-converting enzyme (ACE) and chymase, is increased in biopsies of human aortic aneurysm. 5 In some rodent model studies inhibiting angiotensin II using angiotensin type 1 receptor (ATR1) blockers or ACE inhibitors has been successful in limiting aneurysm development or progression.1,3 Genetic polymorphisms in the ATR1 have been associated with human aortic aneurysm.6 On the basis of these and other data, several trials are underway to assess the efficacy of ATR1 blockers and ACE inhibitors in limiting progression of thoracic and abdominal aortic aneurysm. 3 See accompanying article on page 1568One of the many effects of angiotensin II is to stimulate release of the mineralocorticoid aldosterone from the adrenal cortex. In the current issue of Arteriosclerosis, Thrombosis and Vascular Biology, Liu et al 7 describe studies investigating the role of the mineralocorticoid receptor (MR) in aortic aneurysm and dissection development in C57BL/6 male mice. There were 4 key findings of the study. First, administration of a MR agonist plus salt induced aortic aneurysm and dissection. Second, the aneurysms had some histological features similar to human aortic aneurysm, including elastin degradation, elevated matrix metalloproteinases activity, vascular smooth muscle cell apoptosis, macrophage and neutrophil infiltration, and upregulation of a range of inflammatory and oxidative stress markers. Histological evidence of aortic dissection was also demonstrated in 40% of the mice. Third, MR antagonism attenuated MR agonist and salt-induced aneurysm formation. Fourth, there was no association between the rise in blood pressure induced by MR and salt and the size or incidence of aneurysm development. Administration of an ATR1 blocker or ACE inhibitor did not influence aneurysm incidence despite lowering of blood pressure.Previously published data also support the role of the MR in aneurysm formation. Kanematsu et al 8 reported that administration of the MR agonist deoxycorticosterone acetate plus 1% salt (or ang...

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“…Interestingly, patients who had stopped ACE I therapy prior to admission were more likely www.intechopen.com to present with ruptured AAA 71 . The effect of ACE I on expansion of AAA is still equivocal, with some studies demonstrating no protective effect of ACE I therapy [72][73] . Thompson et al in a recent observational study of 1269 patients with small AAA who were followed up for a mean of 3.4 years, reported a significant reduction in aneurysm growth rate as a result of ACE inhibitor therapy 72 .…”

Section: Medical Treatment Of Patients With Aaamentioning

confidence: 99%

“…The effect of ACE I on expansion of AAA is still equivocal, with some studies demonstrating no protective effect of ACE I therapy [72][73] . Thompson et al in a recent observational study of 1269 patients with small AAA who were followed up for a mean of 3.4 years, reported a significant reduction in aneurysm growth rate as a result of ACE inhibitor therapy 72 . The follow up data from UK small aneurysm trial does not support the above finding 74 .…”

Section: Medical Treatment Of Patients With Aaamentioning

confidence: 99%

The Evidence for Management of Abdominal Aortic Aneurysms: Lessons Learned from Randomised Controlled Trials

Mofidi¹,

Suttie²

2011

Aneurysmal Disease of the Thoracic and Abdominal Aorta

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An analysis of drug modulation of abdominal aortic aneurysm growth through 25 years of surveillance

Cited by 135 publications

References 22 publications

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)

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)

Is There a New Target in the Renin–Angiotensin System for Aortic Aneurysm Therapy?

The Evidence for Management of Abdominal Aortic Aneurysms: Lessons Learned from Randomised Controlled Trials

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