- Pitcher A, et al. MTT - Assessing the effects of ARBs and beta-blockers in Marfan Syndrome. Hot Line Session 9, ESC Congress 2022, Barcelona, Spain, 26–29 August.
The connective tissue disorder Marfan syndrome is associated with characteristic aortic root enlargement, which increases the risk of life-threatening aortic dissection and rupture, sometimes in early adulthood. Elective surgery to replace the aortic root is often discussed with the patient when the aortic root reaches 4.5–5 cm. Limited previous data has led to the recommendation of using beta-blockers to retard aortic growth. However, some clinical evidence also suggests that ARBs might slow aortic root growth in Marfan syndrome.
The Marfan Treatment Trialists’ (MTT) Collaboration set out to retrospectively determine the effects on ARBs and beta-blockers on aortic root growth by means of a meta-analysis, presented by Dr Alex Pitcher (Oxford University Hospitals NHS Foundation Trust, UK), posing 3 research questions1:
Individual data in Marfan patients with no prior aortic surgery was pooled from 7 randomised trials (n=1,442) for these analyses. Firstly, with a median follow-up of 3 years, the researchers saw that treatment with ARBs versus placebo or open control (n=676; average age 29 years, 83% with confirmed pathogenic FBN1 variant; 75% taking beta-blocker at baseline), treatment with ARBs reduced the annual increase of rate of change in the aortic root Z-score to an absolute difference of -0.07 (95% CI -0.12 to -0.01; P=0.012). Aortic dimensions were likewise decreased.
Dr Pitcher paused to summarise this part of the data: “The benefit of ARB therapy was particularly large in patients with an FBN1 mutation at baseline, making it more plausible that the effect is real. There were no other detectable differences in treatment effect depending on other patient characteristics, including age, sex, and blood pressure. The benefit of ARB treatment was similar regardless of whether patients were taking a beta-blocker.”
Secondly, comparing an ARB with a beta-blocker (n=766 patients; average age 14 years; 86% with confirmed pathogenic FBN1 variant; 0% taking beta-blocker at baseline) with a 3-year follow-up, the annual change in the aortic root Z-score was similar in the two groups (absolute difference 0.03; 95% CI -0.05 to 0.10, not significant).
Thirdly, indirect evaluation of the effect of a beta-blocker compared with placebo/control revealed suggestive evidence that being randomised to a beta-blocker approximately halved the annual change in the aortic root Z-score (absolute difference -0.09; 95% CI -0.18 to -0.0033; P=0.04). The researchers concluded that both treatment with ARBs or beta-blockers has clinical benefit, and because these effects are independent, dual therapy may provide an additive benefit to delay aortic root surgery.