Irbesartan in Marfan syndrome (AIMS): a double-blind, placebo-controlled randomised trial
Authors: Michael Mullen, Xu Yu Jin, Anne Child, A Graham Stuart, Matthew Dodd, José Antonio Aragon-Martin, David Gaze, Anatoli Kiotsekoglou, Li Yuan, Jiangting Hu, Claire Foley, Laura Van Dyck, Rosemary Knight, Tim Clayton, Lorna Swan, John D R Thomson, Guliz Erdem, David Crossman, Marcus Flather, John Dean, Bartosz Was, Heather Gow, Jane Murray, Mariella D'Allessandro, Michael Christie, Patricia Cooper, Philip Booth, Sharon Burns, Yvonne Paterson, Ashish Chikermane, Anthony Assing, Catherine Cotter, Gillian Atkins, Helen Williamson, Justin Barclay, Alan Jennison, Alex Henderson, Anna McSkeane, Helen Fairlamb, Julie Kelly, Nicola Kelsall, Scott Prentice, John O'Sullivan, Alison Head-Baister, Angela Phillipson, Anna Johnson, D Crossland, Jack Oliver, Jade Davison, Jill Wake, Louise Quinn, Maureen Foreman, Vera Wealleans, Niki Walker, Alexis Duncan, Evelyn Tibbs, Ruth Kelly, Sachin Khambadkone, Bridget Zotti, Cassie Brady, Elena Cervi, Ella Field, Eszter Szepezvary, Florence Mantey, Gillian Riley, Heather Titmus, Ilaria Bo, Juan Pablo Kaski, Loren Green, Nigel Jones, Rebecca Banks, Christopher Kiesewetter, Sujeev Mathur, Alessandra Frigiola, Alex Savis, Holly Belfield, Josephine Guzman, Julia Harris, Karen Wilson, Kelly Peacock, Kirsty Gibson, Paul Wellman, John Simpson, Saleha Kabir, Sitali Mushemi, Michael Stewart, Bev Atkinson, Cath Richardson, Elaine Leng, Paul Brennan, Annabel Nixon, Collette Spencer, James Oliver, Jan Forster, Louise Turner, Samantha Bainbridge, Anna Maria Choy, Adelle Dawson, Gwen Kiddie, Heather Kerr, Ify Mordi, Jackie Duff, Jacqueline Dunlop, Jonathan Berg, Pauline Armory, Leisa Freeman, Amir Anwar, Charles Graham, Clare London, Gail Healey, Ian Gallagher, Mary Ilsley, Rizwan Ahmed, Sheila Wood, Nigel Wheeldon, Cecilia Mason, Farook Nassim, Janet Middle, Justin Adams, Karen Angelini, Kay Housley, Kim Ryalls, Michael Agyemang, Rachel Walker, Robina Batigan, Tina Bennett, Paul Clift, Amor Mia Alvior, Annette Nilsson, Carole Green, Charlotte Crook, Connie Becani Palmer, Elizabeth Dwenger, Phillipa Doherty, Rebecca Igbokwe, Saba Sharif, Sonia MacDonald, Cathy West, Kevin Kirby, Nitha Naqvi, Sophie Welch, Suad Warsama, Wei Li, Zohreh Farzad, Ben Smith, Victoria Murday, Alexis Duncan, Eamonn Murtagh, Emma Adams, Lesley Armour, Stuart Lilley, Bejal Pandya, Amy Richards, Mervyn Andiapen, Rebecca Macrae, Maite Tome, Carmel Hutchinson, Kameka Angulo, Rooba Kauppayamootoo, Sabiha Gati, Elizabeth Cruddas, William G Newman, Catherine Breen, Dhavendra Kumar, Dirk G Wilson, Adele Farrugia, Alan Fraser, Jayne Sumers, Jessie Powell, Julie Edwards, Terese Hale, Zoe Boult, Aisling Carroll, Gruschen Veldtman, Andrew Ho, David Black, Lisa Fletcher, Sue Mapstone, Tara Bharucha, Gary Marsh, Joanne Jones, Karen Sheehan, Kathleen Selway, Kirsty Stevenson, Martin Nelson, Rebecca Fairweather, Stephanie Curtis, Sue Simpson, Martin Denvir, Audrey White, Jill Steven, Joanna Munro, Wayne Lam, William Toff, Mario Petrou, Paul Silcocks, Raymond MacAllister
Journal: The Lancet (2019)

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.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.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.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.British Heart Foundation, the UK Marfan Trust, the UK Marfan Association.