Marfan syndrome is a connective tissue disease caused by FBN1 gene mutation. Aortic aneurysms and dissections are a major cause of morbidity and mortality in Marfan syndrome.¹ Angiotensin II receptor blockers (ARBs) and beta-blockers (BBs) are used to slow aortic dilatation. Previous meta-analyses did not identify potential adjunctive benefits for ARBs and BBs due to the heterogeneity of published studies.²

Pitcher et al.³ pooled individual patient data from seven randomized clinical trials (1,442 patients). Patients with Marfan syndrome and no prior surgical aortic intervention were included. The primary endpoint was the annual rate of change in aortic root Z score (aortic root dimension adjusted by body surface area).

Patients were followed for a median of 3 years. Four of the seven trials (676 patients, age mean±SD 29±14 years) compared ARBs versus control and patients were permitted to be on BBs. The mean annual rate of change in aortic root Z score in patients taking ARBs versus control was 0.07 (SE 0.02), ARBs versus 0.13 (SE 0.02) control; p=0.012, with absolute difference of 0.07. Comparable results were noted in the secondary analysis regardless of whether the patients were on BBs (heterogeneity p=0.54). The other three trials (766 patients, age mean±SD 14±10 years) compared ARBs versus BBs and the mean annual rate of change in aortic root Z score was –0.08 (SE 0.03) in ARBs group versus –0.11 (SE 0.02) in the BBs group. The mean absolute annual change in the aortic root Z score between BBs and control was −0.09 (95% confidence interval [CI], –0.18 to 0.00; P=0.042), similar to the comparison of ARBs versus control.

This study suggests potential benefits for adjunctive use of ARBs and BBs in Marfan syndrome. However, further studies are warranted to define optimal ARB and BB dosing and to clarify the generalizability of the study findings to other populations including older patients and other etiologies of aortopathies.

References

1. Groth KA, Stochholm K, Hove H, Andersen NH, Gravholt CH. Causes of mortality in the Marfan syndrome (from a nationwide register study). Am J Cardiol 2018;122:1231–35.
2. Al-abcha A, Saleh Y, Mujer M, et al. Meta-analysis examining the usefulness of angiotensin receptor blockers for the prevention of aortic root dilation in patients with the Marfan syndrome. Am J Cardiol 2020;128:101–06.
3. Pitcher A, Spata E, Emberson J, et al; Marfan Treatment Trialists' Collaboration. Angiotensin receptor blockers and β blockers in Marfan syndrome: an individual patient data meta-analysis of randomised trials. Lancet 2022;400:822–31.

Clinical Topics: Cardiac Surgery, Congenital Heart Disease and Pediatric Cardiology, Vascular Medicine, Aortic Surgery, Cardiac Surgery and CHD and Pediatrics, Congenital Heart Disease, CHD and Pediatrics and Quality Improvement

Keywords: ESC Congress, ESC22, Marfan Syndrome, Angiotensin Receptor Antagonists, Confidence Intervals, Body Surface Area, Dilatation, Angiotensin-Converting Enzyme Inhibitors, Aortic Aneurysm, Aortic Diseases, Adrenergic beta-Antagonists, Morbidity, Mutation

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