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Lacro RV, Dietz HC, Sleeper LA, et al. Atenolol versus losartan in children and young adults with Marfan's syndrome. N Engl J Med. 2014;371(22):2061-2071. PMID 25405392

One-paragraph summary

The largest Marfan pharmacotherapy trial: 608 participants aged 6 months–25 years with root z-score >3.0, randomized double-blind at 21 centers (NCT00429364) to losartan or atenolol for 3 years; primary endpoint was the rate of change in BSA-indexed root z-score. Result: −0.107 ± 0.013 (losartan) vs −0.139 ± 0.013 (atenolol) SD/yr, p=0.08 — no difference, and both arms' z-scores declined (root growth slower than body growth on either drug). No differences in 3-year rates of aortic surgery, dissection, death, or their composite.

Key findings

  • Losartan is not superior to beta-blockade in children/young adults — the definitive rebuttal of the mouse-driven expectation that ARBs would outperform (Habashi 2006, PMID 16601194).
  • Both drugs were associated with falling z-scores, but without a placebo arm the absolute benefit of either is not measurable here.
  • Clinical-event rates over 3 years were too low for endpoint conclusions — surrogate-only evidence, again.

Limitations

  • Atenolol dose was titrated to hemodynamic effect while losartan used fixed weight-based dosing — asymmetric optimization is a recurring critique.
  • Young cohort with high baseline z-scores; generalization to older or milder patients uncertain.
  • 3-year horizon vs a disease measured in decades.

Why it matters

Reset the field's expectations after the losartan hype cycle; its data anchor the ARB-vs-beta-blocker limb of the IPD meta-analysis (Pitcher 2022, PMID 36049495), which formalized the conclusion this trial suggested: the two classes are interchangeable at the surrogate level, and the practical question is tolerability and combination, not superiority.

Cited by wiki pages

  • medical-therapy