Antihypertensives reduce the rate of progressive aortic root dilation in Marfan syndrome

1. Compared to control, ARBs reduced the annual rate of increase of the aortic root Z score by approximately one-half.

2. Beta-blockers were shown to have a similar effect on rate of aortic root dilatation compared to ARBs.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Marfan syndrome is a genetic connective tissue disorder which leads to the progressive enlargement of the aorta, specifically the aortic root. Thus, those with Marfan syndrome are at an increased risk of premature death from aortic diseases such as aortic dissection. This meta-analysis analyzed the effect of two common blood pressure medications, angiotensin II receptor blockers (ARBs) and beta-blockers, on the annual rate of increase of the aortic root Z score in patients with Marfan disease. This study analyzed the results from seven randomized controlled trials. During a median follow-up of three years, ARBs were shown to decrease the annual rate of increase of the aortic root Z score by half compared to control. The effect seen was similar between ARBs and beta-blockers. Limitations of this study include the inability to evaluate between different ARB agents or different dosing regimens. Nonetheless, this study provides favourable evidence for the use of ARBs and beta-blockers, potentially in combination, to reduce the rate of progressive aortic root dilatation in those with Marfan disease.

Click to read the study in The Lancet

Relevant Reading: Causes of Mortality in the Marfan Syndrome (from a Nationwide Register Study)

In-Depth [meta-analysis]: A database search of MEDLINE, Embase, and CENTRAL was performed. Eligibility criteria included the involvement of an ARB versus control or ARB versus beta-blocker in patients with Marfan syndrome. In total, seven trials (n=1442) were found to be eligible for study inclusion. The primary outcome assessed was annual rate of change of body surface area-adjusted aortic root Z score measured at the sinuses of Valsalva.

There were four trials that assessed ARB (n = 353) versus control (n = 323) with 75% of participants receiving beta-blockers at baseline. A total of 54% of participants were female with a mean age of 29 years. The median follow-up of these studies was 3 years. In the ARB group compared to the control, there was a reduction in the annual rate of change in the aortic root Z score by almost half (absolute difference -0.07 [95% CI -0.12 to -0.01]; p=0.012). In subgroup analyses, ARBs showed the greatest effect in those with pathogenic variants in fibrillin-1 compared to those without and there was no difference seen with the use of a beta-blocker with an ARB.

The study compared the results of the four trials of ARB versus control to the three trials of ARB versus beta-blockers (n=766) to indirectly assess beta-blockers versus control. The median follow-up for these studies was also 3 years. The change in aortic root Z score between beta-blocker and ARB were similar (annual increase -0.08 in ARB vs -0.11 in beta-blocker). Calculated indirectly, the absolute difference in aortic root Z score between beta-blockers and control was -0.09 (95% CI -0.18 to 0.00; p=0.042).

Image: PD

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