Pediatric Heart Network Trial of Losartan vs. Atenolol in Children and Young Adults with Marfan Syndrome: Impact on Prescription Practices.

The Pediatric Heart Network (PHN) trial showed similar efficacy of ß-blockers (BB) and angiotensin receptor blockers (ARB) for aortic root dilation in Marfan syndrome, but the impact on prescription practices is unknown. We hypothesized BB and ARB prescriptions would increase after the trial results were published (2014). Prescription data (2007-2016) were obtained from outpatient encounters (IBM Marketscan) for Marfan syndrome patients (6 months-25 years old). Excluding 2014 as a washout period, we analyzed two intervals: 2007-2013 and 2015-2016. Medication categories included BB, ARB, angiotensin converting enzyme inhibitors (ACEI), combination (BB/ARB and/or BB/ACEI), and no drug. Interrupted time-series analysis assessed immediate level change after publication and change in slope for the trend pre- and post-publication. Odds ratios (OR) and 95% confidence intervals from logistic regressions and generalized estimating equation methods accounted for correlation of prescriptions within patients. In 1499 patients (age 14.1 ± 6.1 years, 59% female) seen 2007-2013, BB trended lower [OR 0.91 (0.89, 0.93), p < 0.001] and ARB trended higher [OR 1.12 (1.07, 1.18), p < 0.001], while combination, ACEI, and no drug remained stable. This trend persisted, but was not significant, for BB [OR 0.54 (0.27, 1.08), p = 0.37] and ARB [OR 1.91 (0.55, 6.69), p = 0.31] in 2015-2016. Combination, ACEI, and no drug remained similar. In short term follow-up, changes in prescription practices following publication of the PHN trial were not statistically significant. This may be due to a change seen prior to publication with early adoption of ARBs that was maintained after confirmation of their effectiveness.

Atenolol versus losartan in children and young adults with Marfan's syndrome.

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 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 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.).