COMPARE: Does Losartan Reduce Aortic Root Dilatation Rates in Adults With Marfan Syndrome?

"Based on these data alone and given that losartan is a time tested agent, it wouldn't be unreasonable for Marfan patients to begin to take this agent," said Tony DeMaria, MD, MACC.
The addition of losartan to standard beta blocker therapy in adults with Marfan syndrome can reduce aortic root dilatation rates, according to results from the COMPARE Study released on Sept. 1 during the ESC Congress 2013. Losartan was also found to reduce aortic arch dilatation rates in Marfan syndrome adults with aortic root replacements.

The study, based on 233 participants (47 percent female) with Marfan syndrome in the Netherlands, randomized participants to receive either no further treatment, or 50 mg of losartan daily (this amount doubled after 14 days without side effects in 54% of patients). Aortic enlargement was monitored with magnetic resonance imaging (MRI) or CT for three years of follow-up.

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Overall, the study showed that after three years aortic root enlargement was significantly less in the losartan group than in controls (0.77 mm vs. 1.35 mm, p=0.014), and 50 percent of losartan patients showed no growth of the aortic root compared to 31 percent of controls (p=0.022).

In Marfan syndrome aortic enlargement is usually confined to the 'aortic root', but may also extend beyond it. The study showed that aortic enlargement beyond the root was not significantly reduced by losartan. However, among the subset of patients who had already received aortic root replacement, dilation in the aortic arch was significantly lower in patients treated with losartan compared to controls (0.50 mm vs. 1.01 mm; p=0.033).

"Our study is the first large, prospective randomized study to assess the effects of losartan on aortic enlargement in adults with Marfan syndrome, and confirms previous findings in a mouse model," said lead investigator Maarten Groenink MD, PhD, from the Departments of Cardiology and Radiology at Academic Medical Centre in Amsterdam, The Netherlands. "We're very excited to see that such a commonly used drug that is not expensive and has a familiar side-effect profile could have a significant effect on this very serious and frightening risk factor for these patients. These findings may change standard clinical management."

Moving forward, Groenink recommends a larger prospective trial with longer follow-up to determine the relevance of losartan in respect to the treatment on aortic surgery and aortic dissection. He notes that athough the reduced rate of aortic enlargement in the losartan group suggests this drug may postpone or even prevent aortic rupture as well as the need for prophylactic surgery in Marfan patients, the study did not actually demonstrate this result.

Keywords: Losartan, Follow-Up Studies, Heart Defects, Congenital, Dilatation, Pathologic, Heart Valve Diseases, Marfan Syndrome, Netherlands, Risk Factors, Magnetic Resonance Imaging

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