Marfan syndrome: Losartan vs. Atenolol

NEJM 2014 - Online first (Presented at AHA 2014)

Atenolol versus Losartan in Children and Young Adults with Marfan's Syndrome

Lacro RV, et al.

Among children and young adults with Marfan's syndrome who were randomly assigned to losartan or atenolol, we found no significant difference in the rate of aortic-root dilatation between the two treatment groups over a 3-year period.

Angiotensin Receptor Blocker for Marfan Syndrome

NEJM 2008;358:2787-95

(Click on image to enlarge)

18 pediatric patients were treated (17 received Lorsartan, 1 received Ibesartan).

Age range:1 -16 yrs (median age 6.5 yrs)

Duration of study: Median 6 yrs (~4 yrs before starting ARB & ~ 2 yrs after starting ARB)

Dose:

Losartan - started at 0.6 mg/kg/day x 3 wks. Then, gradually increased to 1.4 mg/kg/day.

Ibesartan - started at 1.4 mg/kg/day. Then, gradually increased to 2.0 mg/kg/day.

Check BUN, Creatinine, Electrolytes after 3 months.

ARBs for Marfan Syndrome

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.

Progression of aortic root dilatation was greatly reduced. See figure 2 in the article.