Abstract 16166: Losartan and Atenolol Exert Therapeutic Benefit via Distinct Mechanisms of Action in Marfan Syndrome
Objective: To compare the effects of an angiotensin receptor blocker (ARB) to a β-receptor blocker (BB) on vascular stiffness in adults with Marfan syndrome.
Background: Patients with Marfan syndrome are at risk for aortic aneurysm and dissection. The progressive structural and functional abnormalities of the Marfan aorta may be favorably affected by BBs via decreased ventricular contractility (↓dP/dt) and by ARBs via vascular smooth muscle relaxation and TGFβ inhibition.
Methods: We conducted a randomized, double-blind trial of losartan (100 mg QD) vs. atenolol (50 mg QD) for 6 months in adults with Marfan syndrome. All subjects met Ghent criteria, were over age 18 years, and had no history of aortic events or surgery. Outcome measures assessed by arterial tonometry included augmentation index (AIx) - a measure of central systolic blood pressure augmentation associated with systemic arterial stiffness, and carotid-femoral pulse wave velocity (PWV) - a measure of aortic elasticity. Aortic root and ascending aorta diameters were measured by ultrasound.
Results: 34 subjects (16 male; median age 38 years, IQR 31.5, 48.8) were randomized (17 in each group). There was a comparable decrease in blood pressure in each group (-12.4/-6.7 ± 1.2/0.9 mm Hg with losartan; -11.2/-3.2 ± 1.4/0.9 mm Hg with atenolol; p = ns). Heart rate was reduced by atenolol compared to losartan (-10.0 ± 1.9 vs. 2.1 ± 1.0 bpm; p = 0.01). Losartan significantly decreased (improved) AIx (-8.6 ± 1.0 mm Hg) relative to atenolol (-2.9 ± 0.9 mm Hg) even after correcting for heart rate (p = 0.04). However, PWV decreased (improved) significantly more with atenolol (-1.15 ± 0.20 m/s) than with losartan (-0.22 ± 0.14 m/s; p = 0.04). Change in aortic diameter, measured at the aortic root (-0.06 ± 0.02 cm; -0.04 ± 0.03 cm) and at the ascending aorta (-0.10 ± 0.04 cm; -0.06 ± 0.03 cm), was similar between the losartan and atenolol groups, respectively (p = ns for both).
Conclusions: In adults with Marfan syndrome, 6 months of treatment with losartan improves AIx whereas atenolol is more effective at reducing PWV. That AIx and PWV - both measures of arterial stiffness - were differentially affected by the two treatments suggests that losartan and atenolol exert therapeutic benefit via distinct mechanisms of action.
- © 2013 by American Heart Association, Inc.