Pediatric Heart Network: Atenolol vs. Losartan in Children and Young Adults With Marfan Syndrome

No significant difference in the rate of aortic-root dilation was found in patients with Marfan syndrome who took losartan versus those who took atenolol, according to results of the Pediatric Heart Network trial presented Nov. 18 at AHA 2014 and simultaneously published in the New England Journal of Medicine.

As previous studies have shown losartan to be more effective than beta-blockers in slowing aortic-root enlargement, Ronald V. Lacro, MD, sought to compare the drug to atenolol in children and young adults with Marfan syndrome. The randomized study looked at 608 patients, six months to 25 years of age, with a z-score for maximum aortic-root diameter indexed to body-surface area greater than 3.0, who were randomly assigned to each drug over a three year period, with the primary outcome being the rate of aortic-root enlargement.

Patients who received atenolol (303 participants) began at an initial dose of 0.5mg/kg of body weight, which increased on the basis of hemodynamic response with a maximum dose of 4.0mg/kg per day. Patients taking losartan (305 participants) began at a dosage of 0.4mg/kg of body weight, with a maximum dose of 1.4 mg/kg per day. Each patient received an echocardiogram at baseline, six, 12, 24 and 36 months to measure the aortic-root diameter.

During these visits, patients taking atenolol showed significantly lower resting and average 24 hour heart rates than those taking losartan. After three years, the mean diastolic pressure differed between the groups (54±8 mm Hg, atenolol vs. 56±8 mm HG, losartan), but no difference in systolic or mean blood pressure occurred.

Despite previous studies indicating losartan as the more effective drug in slowing aortic-root enlargement, both groups showed a decrease in aortic-root z-score. Researchers report that there was “no significant difference in the rate of aortic-root dilation.” In addition, no difference was recorded between the age subgroups.

Although researchers did not find losartan to be the more effective treatment, they do repost that “the aortic-root z-score decreased significantly over time in each group, particularly in younger versus older participants, which suggests that there may be added value in beginning therapy relatively early in the disease course.”

In an accompanying editorial, Juan M. Bowen, MD, and Heidi M. Connolly, MD, FACC, note that “it is possible that the atenolol dose used in this trial was more effective than the investigators had anticipated … [However,] losartan appears to be a reasonable treatment option, especially in patients who cannot take beta-blockers.” Both physicians later suggest that the combination of beta-blockers and angiotensin-receptor blockers might work synergistically to achieve even better results.

Keywords: Angiotensin Receptor Antagonists, Losartan, Atenolol, Adrenergic beta-Antagonists, Body Weight, Marfan Syndrome, Blood Pressure, Heart Rate, Echocardiography, AHA Annual Scientific Sessions

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