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Losartan vs. Atenolol to Prevent Aortic Dilation in Marfan Syndrome
Study Questions:
What are the long-term comparative results between atenolol and losartan in the prevention of aortic dilation and complications among patients with Marfan syndrome?
Methods:
A total of 128 patients included in the previous LOAT (LOsartan vs ATenolol) clinical trial (64 in the atenolol group and 64 in the losartan group) were followed for an open-label extension of the study, with the initial treatment maintained. The primary endpoints were change in aortic root and ascending aorta diameter indexed to body surface area on cardiac magnetic resonance (CMR) imaging; secondary endpoints were clinical events including aortic dissection, an indication for aortic intervention or other cardiac surgery, and death.
Results:
Mean clinical follow-up was 6.7 ± 1.5 years. A total of nine events (14.1%) occurred in the losartan group and 12 (18.8%) in the atenolol group. Survival analysis showed no differences in the combined endpoint of need for aortic surgery, aortic dissection, or death (p = 0.462). Aortic root diameter increased with no differences between groups: 0.4 mm/year (95% confidence interval, 0.2-0.5) in the losartan and 0.4 mm/year (95% confidence interval, 0.3-0.6) in the atenolol group. In subgroup analyses, no significant differences were observed after considering age, baseline aortic root diameter, or type of dominant negative versus haploinsufficient FBN1 mutation.
Conclusions:
The long-term monitoring of patients with Marfan syndrome randomly assigned to losartan or atenolol showed no differences between treatment groups in aortic dilation rate or presence of clinical events. The authors concluded that losartan might be a useful, low-risk alternative to beta-blockers in the long-term management of patients with Marfan syndrome.
Perspective:
Beta-blockers are the standard treatment to help prevent aorta dilation and associated clinical events among patients with Marfan syndrome. Recent clinical trials with limited follow-up yielded conflicting results on the effectiveness of losartan as an alternative to beta-blockers. This study suggests no significant difference between therapy with atenolol versus losartan in either the rate of aorta dilation on CMR or clinical events including aortic dissection, an indication for aortic intervention or other cardiac surgery, and death. Especially among patients with Marfan syndrome who are intolerant to beta-blockers, it may be reasonable to try using losartan as an alternative therapy. However, in the absence of concomitant hypertension, it might prove difficult to use high doses of either, and perhaps especially losartan.
Clinical Topics: Cardiac Surgery, Congenital Heart Disease and Pediatric Cardiology, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Prevention, Vascular Medicine, Aortic Surgery, Cardiac Surgery and Arrhythmias, Cardiac Surgery and CHD and Pediatrics, Congenital Heart Disease, CHD and Pediatrics and Arrhythmias, CHD and Pediatrics and Imaging, CHD and Pediatrics and Interventions, CHD and Pediatrics and Prevention, Interventions and Imaging, Interventions and Structural Heart Disease, Interventions and Vascular Medicine, Magnetic Resonance Imaging, Hypertension
Keywords: Adrenergic beta-Antagonists, Aortic Aneurysm, Atenolol, Body Surface Area, Cardiac Surgical Procedures, Diagnostic Imaging, Dilatation, Dissection, Heart Defects, Congenital, Hypertension, Losartan, Marfan Syndrome, Magnetic Resonance Imaging, Primary Prevention, Vascular Diseases
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