AIMS Results Show Irbesartan is Effective in Marfan Syndrome

AIMS Trial Press Release:
Results from the recent Aortic Irbesartan Marfan Study (AIMS) found that the drug Irbesartan reduces aortic dilatation in children and young adults with Marfan syndrome.  
 
Summary of Research Project and Findings
The Aortic Irbesartan Marfan Study (AIMS) was a UK research study carried out in 22 centres that tested the effects of Irbesartan, a commonly used medicine to treat high blood pressure, on aortic size compared to placebo in patients with Marfan syndrome. Marfan syndrome is a condition that often runs in families and is associated with stretching of the aorta which is the main artery that comes out of the heart. Stretching of the aorta is linked to serious complications such as tearing of the inside of the aorta (dissection) which can reach the outside of the aorta (rupture) which can lead to death. Slowing stretching of the aorta in Marfan Syndrome is a common goal of management and most patients with Marfan syndrome have the width of the aorta measured on an annual basis.  
 
In the AIMS trial about 200 patients aged 6-40 years old received either Irbesartan or placebo (inactive treatment that looks like Irbesartan) for about 4 years and had their aortic diameters measured using careful echocardiography (ultrasound) measurements each year. On average Irbesartan was associated with smaller aortic diameters compared to placebo over the 4 year follow up period (about 1mm less over the study period) and was well tolerated by participants that took part in the study. These results indicate that Irbesartan could be used as a strategy to reduce aortic diameter in patients with Marfan Syndrome especially those at higher risk of aortic complications. AIMS was funded by the British Heart Foundation, Marfan Trust and Marfan Association.
 
Scientific Summary
Background
Marfan syndrome is a common dominantly inherited genetic disorder caused by mutations in the gene that encodes for the elastic components of fibrillin-1 which is a key constituent of arterial walls. Cardiovascular complications of Marfan syndrome including dissection and rupture of the aorta, the main blood vessel coming out of the heart, are important causes of premature death and disability. Slowing progression of aortic dilatation is a key target of treatment to improve outcomes in patients with Marfan syndrome.  
 
Experimental models of Marfan syndrome suggest that angiotensin-II receptor blockers could favourably alter biological pathways that contribute to the progression of aortic dilatation.  Previous randomised trials have tested the effects of the angiotensin receptor blocker losartan on aortic dilatation in patients with Marfan syndrome without showing consistent results. 
 
Methods
AIMS was a University/NHS led randomised placebo-controlled trial testing the effect of the angiotensin receptor blocker irbesartan on aortic dilatation in children and young adults with Marfan syndrome. Performed in 22 UK centres. 192 patients age 6-40 years old were randomised to Irbesartan 150-300mg (depending on weight) or matching placebo. Participants had a median age of 18 years with 25% aged between 6 and 11.  Aortic sinus diameter was assessed by transthoracic echocardiography and analysed by an independent core laboratory at baseline and at yearly intervals for up to 5 years. AIMS was unique in that it studied both children and adults and is the only trial to have studied the effect of Irbesartan, a selective angiotensin-1 receptor inhibitor.
 
Results
Irbesartan treatment reduced the rate of aortic dilatation (the primary endpoint) by 0.22 mm/year (95% confidence interval 0.02 to 0.41 mm/year, p=0.030) from 0.74mm/year in the placebo group to 0.53mm/year in patients treated with irbesartan (Figure). See Chart C. There was also evidence of a difference in the rate of change in aortic Z-score which is a measurement correcting for growth. Systolic blood pressure was also reduced in the Irbesartan group.  Irbesartan was well tolerated with no observed differences in adverse events between groups.  There was no difference in the proportion of patients that underwent cardiac surgery.  
 
Conclusions
The AIMS trial has shown that Irbesartan can reduce aortic dilatation in children and young adults with Marfan syndrome.  Further work is needed to understand the clinical impact of this observation to reduce the risk of serious aortic complications like dissection and rupture and potentially improve the quality of life in Marfan syndrome.
 
Organisation of the AIMS Trial
AIMS was an investigator led study sponsored by the Royal Brompton and Harefield NHS Trust, London UK. The study was led by Dr Michael Mullen, consultant cardiologist at the Bart’s Heart Centre and Queen Mary University, London. Funding was through a special project grant from the British Heart Foundation with additional financial support from the UK Marfan Trust and Marfan Association. Irbesartan and matching placebo were supplied under contract by Sanofi Research. The drug was packaged and distributed by Brecon Pharmaceuticals Ltd. The study was managed by the Clinical Trials and Evaluation Unit at Royal Brompton Hospital from 2010 until 2014 and then by the Clinical Trials Unit at the London School of Hygiene and Tropical Medicine from 2014 who also undertook the statistical analysis. The echocardiography core lab was based at John Radcliffe Hospital in Oxford. AIMS was funded by the British Heart Foundation, Marfan Trust and Marfan Association.
 
Also see our case study on how to access Irbesartan
 
AIMS Results Show Irbesartan is Effective in Marfan Syndrome
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