Losartan decreases aortic root dilation in Marfan syndrome. B.S. Brooke, J.P. Habashi, H.C. Dietz. HHMI & Instit. of Genetic Medicine, Johns Hopkins School of Medicine, Baltimore, MD.
   The Marfan Syndrome (MFS) is an autosomal dominant connective tissue disorder caused by mutations in fibrillin-1. The most severe complication of MFS is progressive aortic root enlargement, which leads to dissection or rupture unless surgical repair is undertaken. -blockers are standard medical therapy in these patients and slow aortic growth, but do not prevent the need for surgery. Up to a third of MFS patients are intolerant to -blockers and get switched to other blood-pressure reducing agents during the course of treatment. Recently, data from a mouse model of MFS suggested that over-expression of TGF-signaling contributes to the pathogenesis of aneurysm formation. In this model, aortic dilation was arrested by the use of the angiotensin II type-1 receptor blocker losartan, an antihypertensive medication known to inhibit TGF- signaling. Here, we report the results of an observational study designed to evaluate the effectiveness of losartan therapy in MFS patients with progressive aortic dilation. A total of 12 MFS patients (6 males, 6 females, mean age 86 years) were identified from an institutional database that had been switched from -blocker to losartan between August of 1998 and May of 2006. Serial echocardiographic measurements (mean 10 per pt.) of aortic diameter and corresponding Z-scores were compared for each patient while on -blocker and after initiation of losartan. The mean rate of aortic growth (0.007 cm/yr vs. 0.31 cm/yr; P<0.005) and the mean rate of change in Z-score (-1.40 Z-score/yr. vs. +0.81 Z-score/yr.; P<0.01) were both significantly decreased for individuals on losartan, as compared to their prior performance on -blockers. After adjusting for confounders using multiple linear regression, losartan therapy independently reduced the rate of aortic growth by 0.28 cm per year [95%CI:-0.46 to -0.09; P<0.005]) and reduced the Z-score by 2.14 per year [95%CI:-4.03 to -0.24; P<0.05]. In conclusion, these data suggest that losartan therapy offers a significant advantage over -blockers for the treatment of MFS. A prospective randomized trial will be initiated soon and be important to confirm the results of this study.