October 2022
ARB and beta-blocker effects in Marfan syndrome

Both angiotensin-receptor blockers and beta-blockers slowed the rate of increase in aortic-root size, according to a meta-analysis of individual-level randomised-trial data.

The genetic disorder Marfan syndrome is associated with progressive aortic dilation and the attendant risk for aortic dissection. To assess how angiotensin-receptor blockers (ARBs) and beta-blockers affect progression of aortic-root enlargement, as measured by aortic-root Z scores, investigators conducted an individual-level meta-analysis of randomised trials that had compared ARB with control treatment (typically placebo) or ARB with beta-blocker therapy in patients with Marfan syndrome and no previous aortic surgery. Seven trials were ultimately eligible for analysis: four ARB versus control (676 patients; mean age, 29 years), three ARB versus beta-blocker (766 patients; mean age, 14 years). Median follow up was three years in both sets of trials.

The mean annual increase in aortic-root Z score associated with ARB therapy (+0.07) was about half that for control treatment (+0.13), with no evidence of effect modification by beta-blocker use; 8% of each group experienced aortic dissection, aortic surgery or death during follow up. The mean annual change in aortic-root Z score was also similar between groups in the trials of ARB versus beta-blocker (−0.08 and −0.11, respectively), as was incidence of the composite endpoint (5%, ARB; 4%, beta-blocker).

Comment: In this individual-level meta-analysis, ARBs reduced the rate of increase in aortic-root size, and beta-blocker effects were similar to those of ARBs. The lack of effect modification suggests the two benefits may be additive. Although individual-level data were not available for all randomised trials, conclusions from those trials are consistent with the meta-analysis results. The trials also did not randomly assign patients to particular agents or dosages. Nevertheless, the findings suggest that both therapies may slow the progression of aortic dilation and, thereby, delay the need for aortic surgery in patients with Marfan syndrome.
Professor of Clinical Medicine, University of California San Francisco School of Medicine; Medical Director, Cardiac Stress Laboratory, UCSF Medical Center, San Francisco, USA.

Pitcher A, et al. Angiotensin receptor blockers and beta blockers in Marfan syndrome: an individual patient data meta-analysis of randomised trials. Lancet 2022 Aug 29; e-pub (https://doi.org/10.1016/S0140-6736(22)01534-3).

This summary is taken from the following Journal Watch title: Cardiology.