The clinical relevance of the decelerating effect of angiotensin receptor blockers on aortic growth in Marfan patients; a Bayesian perspective

BACKGROUND: Marfan Syndrome (MFS) often leads to thoracic aortic aneurysm (TAA), for which angiotensin (II) receptor blockers (ARBs) are prescribed to reduce aneurysm growth. Although recent pooled analyses demonstrated a statistically significant reduction in aortic growth with ARBs under a frequentist framework, the clinical relevance of this effect remains uncertain. Moreover, ARB therapy is notably burdensome for patients due to significant side-effects. Therefore, this study re-analyses randomised ARB versus comparator trials in MFS patients, under a Bayesian statistical framework. METHODS: The trials included by the Marfan Treatment Trialists' Collaboration were re-analysed using fixed- and random-effects Bayesian models comparing ARBs to controls. The primary outcome was the mean difference in the annual rate of change of aortic root dimension, adjusted for body surface area (z-score). The minimal clinically important difference (MCID) was applied to assess the clinical relevance of the pooled posterior effect, based on previous consensus and available literature (at 0.12 adjusted z-scores/year). RESULTS: Four randomised trials, comprising 626 patients, were included. Under the fixed-effects model, the pooled mean difference was -0.07 z-score/year [95 % CrI, -0.12; -0.01] in favour of ARBs, though with a posterior probability of a clinically relevant treatment effect of only 7.3 %. Using a Bayesian random-effects model, the pooled mean difference was -0.06 z-score/year [95 % CrI, -0.22 to 0.11] in favour of ARBs, with a similarly low probability of achieving the MCID (18.1 %). CONCLUSIONS: The findings of this Bayesian analysis suggest that ARBs are unlikely to achieve clinically meaningful reductions in aortic growth for MFS patients.