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Shores J, Berger KR, Murphy EA, Pyeritz RE. Progression of aortic dilatation and the benefit of long-term beta-adrenergic blockade in Marfan's syndrome. N Engl J Med. 1994;330(19):1335-1341. PMID 8152445

One-paragraph summary

Open-label randomized trial in 70 adolescents and adults with classic Marfan syndrome (32 propranolol, 38 control), followed ~10 years (9.3 control / 10.7 treated), with individualized propranolol dosing (mean 212 ± 68 mg/day) targeted to blunt dP/dt and heart rate. The regression slope of aortic-root dimension was 0.023/yr on treatment vs 0.084/yr in controls (p<0.001); clinical endpoints (aortic regurgitation, dissection, cardiovascular surgery, heart failure, death) occurred in 5 treated vs 9 control patients, with Kaplan-Meier curves favoring treatment during the middle trial years. Intention-to-treat analysis of all 70 patients.

Key findings

  • First randomized evidence that any medication slows aortic-root dilation in Marfan syndrome (~4-fold reduction in growth slope).
  • Effect achieved with aggressive, hemodynamically titrated beta-blockade — doses far above typical modern practice.
  • Underpowered for clinical endpoints; benefit is on a surrogate.

Limitations

  • n=70, open-label, single center; adolescent/adult "classic" Marfan only (subsequent trials suggest heterogeneous response).
  • Slope metric (dimensionless regression on normalized root dimension) complicates comparison with later mm/yr and z-score endpoints.
  • A 2006 meta-analysis pooling this trial with observational cohorts found no demonstrable clinical-outcome benefit of beta-blockade (Gersony 2007, PMID 16831475), underscoring how much of the beta-blocker standard rested on this one small trial.

Why it matters

Established beta-blockade as standard prophylaxis in Marfan for two decades and set the surrogate-endpoint template (root-growth slope) that every subsequent ARB trial and the 2022 IPD meta-analysis (Pitcher 2022, PMID 36049495) inherited; it remains half of the current Class 1 LOE A recommendation (beta-blocker or ARB) in the 2022 ACC/AHA guideline (PMID 36322642).

Cited by wiki pages

  • medical-therapy