Marfan syndrome - AIMS

The clinical question

Marfan syndrome is an inherited condition that affects connective tissue, which provides the structural framework that holds the body’s cells in place. People with Marfan syndrome are often very tall.  The condition can also affect the joints, spine and eyes.

But the most serious complications of Marfan syndrome are caused by weak blood vessels - in particular, weakness of the ‘aortic root’. This is the part of the main artery in the body that is connected to the heart. The weakened aortic root expands with age and can tear or burst. This is called an aortic dissection and causes major bleeding – a life threatening emergency.

Drugs called beta blockers have been shown to slow this expansion of the aorta. But many people with Marfan syndrome also have asthma, which can be made worse by beta blockers. Previous studies had suggested that the angiotensin receptor blocker irbesartan, a drug normally used to treat high blood pressure, might also be able to slow the expansion of the aorta.

Together with the Marfan Trust, the BHF funded the AIMS trial (‘A prospective, randomised placebo-controlled double blind multi-centre study of the effects of irbesartan on aortic dilatation in Marfan syndrome’), led by Dr Michael Mullen, at University College London. The trial aimed to find out whether irbesartan could be ‘repurposed’ to treat people with Marfan Syndrome, potentially with fewer side effects than beta blockers.

What did the study involve?

Between 2010 and 2015, the AIMS trial recruited 192 people with Marfan syndrome. Participants were aged 6 to 40 years and were from around the UK, and were randomly allocated to:

• Take irbesartan over 3 to 5 years.
• Take an inactive placebo.

All participants continued taking their routinely prescribed treatments, including beta blockers if possible. 

For the first 6 months, the participants had monthly medical visits to check how they were responding to the treatment and to adjust the dose if necessary. They then had yearly medical visits where the diameter of the aortic root was measured using echocardiography. The team also checked if participants were taking their treatment, and measured blood pressure, heart and liver function. 

What did the study show?

• The rate of expansion of the aortic root was reduced by 30% in the irbesartan group compared with the placebo group.

• Irbesartan also seemed to be safe.

Why is the study important?

AIMS is the first clinical trial to test the effects of irbesartan on aortic root expansion in Marfan syndrome.

Dr Mullen, who presented the results of AIMS at the 2018 European Society of Cardiology Conference in Munich, commented: “These results are encouraging for all the people living with Marfan syndrome as a previous clinical trial published in 2014 and testing a drug from the same family as irbesartan but less potent, called Iosartan, failed to slow the rate of aortic enlargement.”

Study details

"A prospective, randomised, placebo-controlled double blind, multi-centre study of the effects of Irbesartan on aortic dilation in Marfan syndrome (AIMS)" 
Award reference:  SP/09/006/25108
Principal Investigator: Dr Michael Mullen, Imperial College London
Trial registration number: ISRCTN90011794

Publication details

Mullen M, Jin XY, Child A, et al. Irbesartan in Marfan syndrome (AIMS): a double-blind, placebo-controlled randomised trial. Lancet. 2020;394(10216):2263-2270.