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Adding an angiotensin II-receptor blocker to traditional treatment for Marfan's syndrome may slow the disease.
A recent investigation suggests that adding losartan or another angiotensin II-receptor blocker (ARB) to the traditional beta-blocker regimen used to prevent aortic aneurysm in patients with Marfan's syndrome may slow the rate of progressive aortic-root dilation characteristic of this disease.
The study was conducted in 18 youngsters with Marfan's syndrome; they ranged in age from 14 months to 16 years and were patients at the genetics clinic of Johns Hopkins Hospital in Baltimore, where they received beta-blockers and underwent echocardio-
graphic measurements of aortic segments. In 17 of the patients, ARB therapy was initiated with losartan, at an initial oral dose of 0.6 mg/kg/day, increased over a three-week period to 1.4 mg/kg/day. The 18th patient received another ARB, irbesartan, at an initial dose of 1.4 mg/kg/day and a final dose of 2.0 mg/kg/day. Beta-blocker therapy was continued in all patients.
Patients receiving ARB and beta-blockers were followed for a median of 26.1 months, and had a median of five echocardiograms. The rate of change in aortic root diameter fell among all patients after ARB therapy began, including the single patient treated with irbesartan. The decrease was estimated at 2.75 mm per year, compared with beta-blockers alone.
The rate of change of the sinotubular junction, an aortic segment that is also prone to dilation in patients with severe Marfan's syndrome, also benefited from ARB therapy. In comparison, more distal aortic segments not typically affected in Marfan's syndrome continued to show an annual rate of change in diameter that was appropriate for age and body size.
Underscoring the benefit of ARB, mean rates of change in aortic root diameter and z scores at the study's end were significantly higher in the control group of 65 patients who received beta-blocker therapy alone than in those who received ARB and beta-blockers. Overall, patients in the beta-blocker group had milder aortic root disease than those in the ARB group.
ARB therapy was not associated with adverse events or side effects, though the rate of change of increase in body height declined after ARB therapy was initiated (Brooke BS et al: N Engl J Med 2008;
The authors caution that this retrospective study is preliminary and needs to be confirmed by an ongoing prospective, randomized, controlled study. In about 15 years, this group has gone from identifying the genetic basis of Marfan's syndrome to clarifying its pathophysiology based on the genetic defect-and now, using the new knowledge, to propose medical treatment for complications of the disease. This is an exciting example of how understanding the human genome will change medicine at your patient's bedside.
DR. BURKE, section editor for Journal Club, is chairman of the department of pediatrics at Saint Agnes Hospital, Baltimore. He is a contributing editor for Contemporary Pediatrics. He has nothing to disclose in regard to affiliations with, or financial interests in, any organization that may have an interest in any part of this article.