Angiotensin Receptor Blockers Show Significant Reduction of Aortic Root Enlargement in a Meta-Analysis of Trials
The Marfan Foundation Statement
A meta-analysis of seven global clinical trials with data from 1442 participants with Marfan syndrome has been completed and published today in The Lancet. The primary aim of the meta-analysis was to estimate the effects of angiotensin receptor blockers (ARB) and beta-blockers on the rate of aortic root enlargement patients with Marfan syndrome. The results indicate that ARBs (such as losartan and irbesartan) significantly reduce the rate of aortic enlargement by about half with or without beta-blockers. This effect was generalizable to different types of patients. In particular, ARBs were effective even among those already taking a beta-blocker. The rate-reducing effect was particularly large among patients with a disease-causing (pathogenic) FBN1 gene mutation compared to those without an FBN1 variant, providing biological support for the effect.
The study also provided indirect evidence supporting the use of beta-blockers in Marfan syndrome, adding to the evidence already available for this treatment.
The authors included the global trial leaders from the United Kingdom, Canada, Spain, United States, Netherlands, and Belgium.
“The results of this meta-analysis show that ARBs reduced the rate of increase in aortic size in these trials by about half, and there was no evidence that the effect size depended on use of beta-blockers,” said Alex Pitcher, DPhil, Oxford University Hospital, the lead author of the study.
The authors suggest that, if tolerated, the combination therapy of beta-blockers and ARBs would reduce the rate of aortic enlargement by at least one half, and potentially much more if therapy were maintained over a sustained period. As a result, the need for surgery may be substantially delayed.
Information on the Study Design of the Meta-Analysis
Because of the differences in trial designs, the meta-analysis compared data from the seven trials in two groups. In the first group of trials, involving 676 eligible participants, ARBs were compared to placebo or control. During a median follow-up of three years, participants on ARB experienced approximately half the annual rate of change in the aortic root Z-score compared to the rate experienced by patients taking placebo or control treatment.
The meta-analysis then analyzed three trials whose design compared ARBs with beta- blockers involving 766 eligible participants. During a median follow-up of three years, the annual change in the aortic root Z-score was similar in the two groups.
By comparing the results of these two types of study, the researchers could make an indirect estimate of the effects of beta-blockers. They concluded that beta-blockers had a similar beneficial effect to that seen by ARBs. Because there were no trials comparing a beta-blocker to a control group (no drug) in this study, and the beta-blocker analyses depended on indirect comparisons of two groups of trials, the authors were more cautious in their interpretation of the beta-blocker results than they were about the ARB results, which were the result of direct analyses.
The Marfan Foundation
Supporting research is one of The Marfan Foundation’s critical mission areas. Providing funding to Alex Pitcher and his colleagues at Oxford University to take on this challenging task of analyzing all eligible trials for which data was available will provide significant clarity for therapeutic options for our patient community and help to improve the lives of those with genetic and vascular conditions.