Abstract 21342: Angiotensin II Blockade and Beta-Blockade Combination Therapy Slows Down the Aortic Root Dilatation in Patients with Marfan Syndrome
Introduction: Beta-blockade, the standard treatment for Marfan syndrome (MFS), had limited effects in aortic root growth. Losartan, an angiotensin II blockade (ARB), had potential efficacy to prevent aortic root dilatation in an animal model of MFS.
Hypotheses. Combination therapy with ARB and beta-blockade has synergic effects on attenuation of aortic root dilation in patients with MFS.
Methods: A randomized, open-label, active control trial was conducted in National Taiwan University Hospital. From May 2007 to Jan 2010, twenty-eight patients (M/F: 12/16, 16.5 ± 6.6 years) diagnosed as MFS with recognized aortic root dilation (Z score >2.0) and under beta-blockade were enrolled and randomized into two groups. One group continued previous beta-blocker therapy. The other group received a combination therapy with beta-blocker and ARB. The study medication, Losartan, was prescribed with a starting dose and then titrated to an optimal dose in one to two weeks according to the resting heart rate and blood pressure. The dose of beta-blocker, Atenolol / Propranolol, was shifted to low maintenance dose (50 mg of Atenolol once daily or 20 mg of Propranolol twice daily for adults and 1 mg/Kg/day for children) in order to reduce the drug-drug interaction and reach the optimal Losartan dose.
Results: The combination therapy with ARB and beta-blockade effectively slowed down the growth rate of aortic root as compared to beta-blockade alone (0.21 mm/yr versus 1.14 mm/yr, p = 0.018). The changes of the aortic diameters at sinus of Valsalva and annulus showed the same trend with a reduced rate of change in those receiving combination therapy (p = 0.027 and 0.047, respectively). Among those with combination therapy, five (33%) were even noted to have reduced size of the aortic root. However, the changes in aortic distensibility and cross-sectional compliance were similar between the two groups. The adverse effects from the combination therapy were not significantly different as compared to beta-blockade alone.
Conclusion: The combination therapy with ARB and beta-blockade may provide more effective and safe protection to slow down and even reduce the aortic root diameter than sole beta-blockade in patients with MFS.
- © 2010 by American Heart Association, Inc.