NEJM 2008;358_2787-95 (Free full text)Angiotension II blockade and aortic root dilatation in Marfan syndrome.
Deficiency of fibrillin-1 in extracellular matrix leads to excessive signalling by TGF-beta. This may be the pathogenic mechanism for phenotypic features - including aortic root dilatation (mouse model). ARBs are known to inhibit TGF-beta. Therefore, in this non-randomized study, 18 children - mean age 6.5 yrs, range 1-16 yrs - who showed progressive dilatation of aortic root in spite of beta-blocker therapy were given ARBs.
Losartan started at 0.6 mg/kg/day x 3 weeks. If no side effects, dose was slowly increased to 1.4 mg/kg/day. (If the patient was receiving calcium-channel blocker, it was stopped when Losartan was started).
Or
Irbesartan at 1.4 mg/kg/day, increased upto 2 mg/kg/day.
Irbesartan at 1.4 mg/kg/day, increased upto 2 mg/kg/day.
Progression of aortic root dilatation was greatly reduced. See figure 2 in the article.
