Atenolol versus Losartan in Children and Young Adults with Marfan's Syndrome

Abstract

BACKGROUND Aortic-root dissection is the leading cause of death in Marfan's syndrome. Studies suggest that with regard to slowing aortic-root enlargement, losartan may be more effective than beta-blockers, the current standard therapy in most centers. METHODS We conducted a randomized trial comparing losartan with atenolol in children and young adults with Marfan's syndrome. The primary outcome was 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 3-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. RESULTS From January 2007 through February 2011, a total of 21 clinical centers enrolled 608 participants, 6 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 (±SE) in the 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 degree of aortic-root dilatation relative to body-surface area with either treatment. The 3-year rates of aortic-root surgery, aortic dissection, death, and a composite of these events did not differ significantly between the two treatment groups. CONCLUSIONS Among children and young adults with Marfan's syndrome who were randomly assigned to losartan or atenolol, we found no significant difference in the rate of aortic-root dilatation between the two treatment groups over a 3-year period. (Funded by the National Heart, Lung, and Blood Institute and others; ClinicalTrials.gov number, NCT00429364.)

Local Application of Leptin Antagonist Attenuates Angiotensin II–Induced Ascending Aortic Aneurysm and Cardiac Remodeling

“…The prominent role of AngII in cardiovascular remodeling has positioned renin angiotensin aldosterone system antagonists as front‐line therapy for ATAA, LVH, and advanced AVS52, 53, 54; however, systemic therapy with AngII receptor blockers or angiotensin‐converting enzyme inhibitors have achieved limited success, especially in attenuating ATAA expansion and AVS progression. In contrast, we have witnessed promising results in AngII‐infused mice receiving LepA at the ascending aorta.…”

Trends in Congenital Heart Disease

“…75,103,104 Targeted questions in cardiac surgical practice and pharmacological treatment of CHD, Kawasaki disease, and Marfan syndrome have been addressed using high-quality randomized clinical trials under the auspices of the PHN. 12,13,[105][106][107] New approaches to investigation of clinical practice are likely to increasingly use models of collaborative, structured learning in the field, such as Standardized Clinical Assessment and Management Plans, which have proved valuable in collecting and analyzing data on common conditions in which there is significant variation of clinical practice. [109][110][111] In addition, registries (see below) will continue to enable research on conditions that are not well suited to randomized, controlled trials.…”

The pathology and pathobiology of bicuspid aortic valve: State of the art and novel research perspectives

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