Randomized, Double-blind Study for the Evaluation of the Effect of Losartan Versus Placebo on Aortic Root Dilatation in Patients With Marfan Syndrome Under Treatment With Beta-blockers
Randomized, Double-blind Study for the Evaluation of the Effect of Losartan Versus Placebo on Aortic Root Dilatation in Patients With Marfan Syndrome Under Treatment With Beta-blockers
To study the effect of losartan (an angiotensin receptor blocker-ARB) on aortic root growth
 in patients with Marfan syndrome, already treated with beta-blockers (BB). The effect of
 losartan will be compared to placebo. Losartan or placebo will be added to the treatment
 regimen in a two-step up-titration scheme over 2 weeks. Start doses of Losartan will be 25 mg
 for subjects under 50kg of weight and 50mg if the weight is over 50kg. Uptitration will be
 guided by the tolerance of the drug by the patients. Patients will be contacted by phone call
 for assessment of side-effects before second step of uptitration.

 Daily maximal doses of Losartan will be 50mg for subjects under 50kg of weight and 100mg if
 the weight is over 50kg
Inclusion Criteria:

 -  Patients > 10 years

 -  Diagnosis of MFS, according to the Ghent criteria and/or genetically proven FBN1
 mutations or linkage

 -  Consent obtained (written) either for the patient and for his/her parents (<18y

 -  Z-score of the aorta at the level of the sinus of Valsalva ≥2 (BSA adjusted)

 -  ARB naïve patients

 Exclusion Criteria:

 -  Poor echocardiographic window,limiting the accurate measurement of the aortic root

 -  Contra-indication for ARB: Bilateral renal artery stenosis, renal function
 abnormalities (creatinine above normal for age), hyperkalemia

 -  Intolerance for ARB (eg angioedema)

 -  Pregnancy or breast feeding women

 -  Absence of effective contraception

 -  Liver function abnormalities

 -  Heart Failure

 -  Patients included in other clinical trial