Angiotensin receptor blockers (ARBs) reduce the rate of aortic root enlargement by about 50% in patients with Marfan syndrome and no previous aortic surgery, including in those taking a β blocker, according to a study published in the Lancet.
Researchers conducted a meta-analysis of trials with patient-level data available that involved a randomized comparison of an ARB vs a control group or an ARB vs a β blocker in patients with Marfan syndrome. A systematic search was performed in MEDLINE, Embase, and CENTRAL from database inception to November 2, 2021.
The prespecified primary outcome was the annual rate of change of body surface area (BSA)-adjusted aortic root dimension Z score as measured at the sinuses of Valsalva.
The analysis included 7 trials with individual data from 1442 participants. Data for the primary analysis were available from 4 trials (676 patients) of ARB vs a control group, and the participants in these trials had a mean age of 29±14 years, 54% were women, and 75% were receiving β blockers at baseline.
The mean baseline Z score was 3.76±2.14 in patients who received an ARB and 3.64±1.94 in patients in the control group. The mean annual change in Z score after a mean 3-year follow-up was 0.07 (SE, 0.02) in the ARB group and 0.13 (SE, 0.02) in the control group, for a mean difference of -0.07 (95% CI, -0.12 to -0.01; P =.012), which is about one-half of the annual rate of change in the aortic root Z score in the ARB group compared with the control group.
No evidence of heterogeneity was observed in the overall results of the 4 trials (heterogeneity P =.11), although significant heterogeneity occurred regarding treatment effects with an ARB between the 490 participants with a documented pathogenic variant in fibrillin-1 (FBN1)compared with the 95 participants who did not have the variant (heterogeneity P =.0050). The mean annual change in aortic root Z score was comparable regardless of whether patients received a β blocker at baseline (heterogeneity P =.54).
In a secondary outcome of absolute aortic dimension, the mean annual change was 0.38 mm (SE, 0.04) in patients who received an ARB and 0.52 mm (SE, 0.04) in patients in a control group, for a mean difference of -0.14 mm (95% CI, -0.26 to -0.02; P =.025).
In 3 trials for which individual participant data were available for ARB vs β blockers (384 ARB and 382 β blocker), the participants had a mean age of 14±10 years, 44% were women, and 86% of genotyped individuals had a pathogenic variant in FBN1. The baseline mean Z score was 4.18±1.71 in patients who received an ARB and 4.03±1.50 in those who received a β blocker. The mean annual Z score change during follow-up was -0.08 (SE, 0.03) in the ARB group and -0.11 (SE, 0.02) in the β-blocker group. The mean difference was not significant between the 2 groups (0.03 [95% CI, -0.05 to 0.10]; P =.48]).
Study limitations include all trial datasets not being available for individual data analysis. Also, 1 trial uses irbesartan, and the others uses losartan. Furthermore, no trials randomly allocated participants to prespecified ARB dosing strategies or to different agents, and the number of patients who had major clinical outcomes is too small to provide sufficient statistical power to detect benefit on such outcomes in the relatively short duration of the trials.
“Assuming additivity, combination therapy with both ARBs and β blockers from the time of diagnosis would provide even greater reductions in the rate of aortic enlargement than either treatment alone, which, if maintained over a number of years, would be expected to lead to a delay in the need for aortic surgery,” the study authors wrote.
Disclosure: One of the study authors declared an affiliation with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Pitcher A, Spata E, Emberson J, et al. Angiotensin receptor blockers and β blockers in Marfan syndrome: an individual patient data meta-analysis of randomised trials. Lancet. Published online August 29, 2022. doi: 10.1016/S0140-6736(22)01534-3