TY - JOUR
T1 - Irbesartan in Marfan syndrome (AIMS)
T2 - a double-blind, placebo-controlled randomised trial
AU - Mullen, Michael
AU - Jin, Xu Yu
AU - Child, Anne
AU - Stuart, A. Graham
AU - Dodd, Matthew
AU - Aragon-Martin, José Antonio
AU - Gaze, David
AU - Kiotsekoglou, Anatoli
AU - Yuan, Li
AU - Hu, Jiangting
AU - Foley, Claire
AU - Van Dyck, Laura
AU - Knight, Rosemary
AU - Clayton, Tim
AU - Swan, Lorna
AU - Thomson, John D.R.
AU - Erdem, Guliz
AU - Crossman, David
AU - Flather, Marcus
AU - Dean, John
AU - Was, Bartosz
AU - Gow, Heather
AU - Murray, Jane
AU - D'Allessandro, Mariella
AU - Christie, Michael
AU - Cooper, Patricia
AU - Booth, Philip
AU - Burns, Sharon
AU - Paterson, Yvonne
AU - Chikermane, Ashish
AU - Assing, Anthony
AU - Cotter, Catherine
AU - Atkins, Gillian
AU - Williamson, Helen
AU - Barclay, Justin
AU - Jennison, Alan
AU - Duncan, Alexis
AU - Simpson, John
AU - Stewart, Michael
AU - Brennan, Paul
AU - Turner, Louise
AU - Choy, Anna Maria
AU - Dawson, Adelle
AU - Kiddie, Gwen
AU - Mordi, Ify
AU - Dunlop, Jacqueline
AU - Berg, Jonathan
AU - Armory, Pauline
AU - Li, Wei
AU - Black, David
N1 - Funding Information:
Data from the AIMS trial, including patient-level data, can be made available on request to established research groups for the purpose of improving human health with an appropriate data sharing agreement. Please contact the corresponding author for data sharing. Acknowledgments We acknowledge support from the trial sponsor (Royal Brompton and Harefield NHS Foundation Trust) and trial coordinating centres (Clinical Trials and Evaluation Unit, Royal Brompton and Harefield NHS Foundation Trust 2010–15 and Clinical Trials Unit, London School of Hygiene and Tropical Medicine 2015–19). We would like to thank all the patients who participated and investigators at participating centres, steering committee, data monitoring committee, and clinical events adjudicators ( appendix p 3 ). We would also like to thank Rebecca Swinson (London School of Hygiene & Tropical Medicine), who provided trial management during follow-up, Tom Godec and Chris Frost (London School of Hygiene & Tropical Medicine), who provided advice on the statistical analysis plan, and Fiona Nugara, Wajid Aslan, and the late Eva Matesanz at the Clinical Trials and Evaluation Unit, Royal Brompton and Harefield NHS Foundation Trust for data management. Sanofi provided irbesartan and placebo at reduced cost and Brecon Pharmaceuticals provided drug packaging, storage, and distribution services.
Publisher Copyright:
© 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2019/12/21
Y1 - 2019/12/21
N2 - Background: Irbesartan, a long acting selective angiotensin-1 receptor inhibitor, in Marfan syndrome might reduce aortic dilatation, which is associated with dissection and rupture. We aimed to determine the effects of irbesartan on the rate of aortic dilatation in children and adults with Marfan syndrome. Methods: We did a placebo-controlled, double-blind randomised trial at 22 centres in the UK. Individuals aged 6–40 years with clinically confirmed Marfan syndrome were eligible for inclusion. Study participants were all given 75 mg open label irbesartan once daily, then randomly assigned to 150 mg of irbesartan (increased to 300 mg as tolerated) or matching placebo. Aortic diameter was measured by echocardiography at baseline and then annually. All images were analysed by a core laboratory blinded to treatment allocation. The primary endpoint was the rate of aortic root dilatation. This trial is registered with ISRCTN, number ISRCTN90011794. Findings: Between March 14, 2012, and May 1, 2015, 192 participants were recruited and randomly assigned to irbesartan (n=104) or placebo (n=88), and all were followed for up to 5 years. Median age at recruitment was 18 years (IQR 12–28), 99 (52%) were female, mean blood pressure was 110/65 mm Hg (SDs 16 and 12), and 108 (56%) were taking β blockers. Mean baseline aortic root diameter was 34·4 mm in the irbesartan group (SD 5·8) and placebo group (5·5). The mean rate of aortic root dilatation was 0·53 mm per year (95% CI 0·39 to 0·67) in the irbesartan group compared with 0·74 mm per year (0·60 to 0·89) in the placebo group, with a difference in means of −0·22 mm per year (−0·41 to −0·02, p=0·030). The rate of change in aortic Z score was also reduced by irbesartan (difference in means −0·10 per year, 95% CI −0·19 to −0·01, p=0·035). Irbesartan was well tolerated with no observed differences in rates of serious adverse events. Interpretation: Irbesartan is associated with a reduction in the rate of aortic dilatation in children and young adults with Marfan syndrome and could reduce the incidence of aortic complications. Funding: British Heart Foundation, the UK Marfan Trust, the UK Marfan Association.
AB - Background: Irbesartan, a long acting selective angiotensin-1 receptor inhibitor, in Marfan syndrome might reduce aortic dilatation, which is associated with dissection and rupture. We aimed to determine the effects of irbesartan on the rate of aortic dilatation in children and adults with Marfan syndrome. Methods: We did a placebo-controlled, double-blind randomised trial at 22 centres in the UK. Individuals aged 6–40 years with clinically confirmed Marfan syndrome were eligible for inclusion. Study participants were all given 75 mg open label irbesartan once daily, then randomly assigned to 150 mg of irbesartan (increased to 300 mg as tolerated) or matching placebo. Aortic diameter was measured by echocardiography at baseline and then annually. All images were analysed by a core laboratory blinded to treatment allocation. The primary endpoint was the rate of aortic root dilatation. This trial is registered with ISRCTN, number ISRCTN90011794. Findings: Between March 14, 2012, and May 1, 2015, 192 participants were recruited and randomly assigned to irbesartan (n=104) or placebo (n=88), and all were followed for up to 5 years. Median age at recruitment was 18 years (IQR 12–28), 99 (52%) were female, mean blood pressure was 110/65 mm Hg (SDs 16 and 12), and 108 (56%) were taking β blockers. Mean baseline aortic root diameter was 34·4 mm in the irbesartan group (SD 5·8) and placebo group (5·5). The mean rate of aortic root dilatation was 0·53 mm per year (95% CI 0·39 to 0·67) in the irbesartan group compared with 0·74 mm per year (0·60 to 0·89) in the placebo group, with a difference in means of −0·22 mm per year (−0·41 to −0·02, p=0·030). The rate of change in aortic Z score was also reduced by irbesartan (difference in means −0·10 per year, 95% CI −0·19 to −0·01, p=0·035). Irbesartan was well tolerated with no observed differences in rates of serious adverse events. Interpretation: Irbesartan is associated with a reduction in the rate of aortic dilatation in children and young adults with Marfan syndrome and could reduce the incidence of aortic complications. Funding: British Heart Foundation, the UK Marfan Trust, the UK Marfan Association.
UR - http://www.scopus.com/inward/record.url?scp=85076749501&partnerID=8YFLogxK
U2 - 10.1016/S0140-6736(19)32518-8
DO - 10.1016/S0140-6736(19)32518-8
M3 - Article
C2 - 31836196
AN - SCOPUS:85076749501
SN - 0140-6736
VL - 394
SP - 2263
EP - 2270
JO - The Lancet
JF - The Lancet
IS - 10216
ER -