Affecting approximately one in 5000 people, Marfan syndrome is an autosomal dominant disorder of connective tissue of the body. Individuals with Marfan syndrome can develop aortic dilation, which can lead to aortic rupture (bursting) or even death. Though beta-blockers are the current standard of therapy for slowing aortic-root enlargement in these individuals, other studies have suggested that losartan may be more effective.
Pediatric Heart Network Investigators conducted one of the largest randomized trials in children and young adults with Marfan syndrome comparing losartan with atenolol, a beta-blocker, to find no significant difference in the rate of aortic-root dilatation between the two treatment groups over a three-year period.
Investigators measured the rate of aortic-root enlargement, expressed as the change in the maximum aortic-root-diameter z score indexed to body-surface area (hereafter, aortic-root z score) over a three-year period. Secondary outcomes included the rate of change in the absolute diameter of the aortic root; the rate of change in aortic regurgitation; the time to aortic dissection, aortic-root surgery, or death; somatic growth; and the incidence of adverse events.
From January 2007 through February 2011, a total of 21 clinical centers enrolled 608 participants, six months to 25 years of age (mean [±SD] age, 11.5±6.5 years in the atenolol group and 11.0±6.2 years in the losartan group), who had an aortic-root z score greater than 3.0. The baseline-adjusted rate of change in the mean (±SE) aortic-root z score did not differ significantly between the atenolol group and the losartan group (−0.139±0.013 and −0.107±0.013 standard-deviation units per year, respectively; P=0.08).
Both slopes were significantly less than zero, indicating a decrease in the aortic-root diameter relative to body-surface area with either treatment. The three-year rates of aortic-root surgery, aortic dissection, death, and a composite of these events did not differ significantly between the two treatment groups.
Compared to other smaller studies that have shown a benefit of losartan therapy, this study directly compared losartan with a beta-blocker versus comparing combination therapy with a beta-blocker alone. It also included similar blood pressures versus differential lowering in the treatment groups, included both children and young adults versus adults alone, and excluded patients with prior aortic surgery rather than including such patients.
Studies such as this provide important insights into different treatments. They also help to shape recruitment, retention, and adherence, and improve the quality of future complex trials involving rare conditions.
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