Design and rationale of a prospective, collaborative meta-analysis of all randomized controlled trials of angiotensin receptor antagonists in Marfan syndrome, based on individual patient data: A report from the Marfan Treatment Trialists' Collaboration

Alex Pitcher, Jonathan Emberson, Ronald V. Lacro, Lynn A. Sleeper, Mario Stylianou, Lynn Mahony, Gail D. Pearson, Maarten Groenink, Barbara J. Mulder, Aeilko H. Zwinderman, Julie De Backer, Anne M. De Paepe, Eloisa Arbustini, Guliz Erdem, Xu Yu Jin, Marcus D. Flather, Michael J. Mullen, Anne H. Child, Alberto Forteza, Arturo EvangelistaHsin Hui Chiu, Mei Hwan Wu, George Sandor, Ami B. Bhatt, Mark A. Creager, Richard B. Devereux, Bart Loeys, J. Colin Forfar, Stefan Neubauer, Hugh Watkins, Catherine Boileau, Guillaume Jondeau, Harry C. Dietz, Colin Baigent

Research output: Contribution to journalArticle

29 Scopus citations


Rationale A number of randomized trials are underway, which will address the effects of angiotensin receptor blockers (ARBs) on aortic root enlargement and a range of other end points in patients with Marfan syndrome. If individual participant data from these trials were to be combined, a meta-analysis of the resulting data, totaling approximately 2,300 patients, would allow estimation across a number of trials of the treatment effects both of ARB therapy and of β-blockade. Such an analysis would also allow estimation of treatment effects in particular subgroups of patients on a range of end points of interest and would allow a more powerful estimate of the effects of these treatments on a composite end point of several clinical outcomes than would be available from any individual trial. Design A prospective, collaborative meta-analysis based on individual patient data from all randomized trials in Marfan syndrome of (i) ARBs versus placebo (or open-label control) and (ii) ARBs versus β-blockers will be performed. A prospective study design, in which the principal hypotheses, trial eligibility criteria, analyses, and methods are specified in advance of the unblinding of the component trials, will help to limit bias owing to data-dependent emphasis on the results of particular trials. The use of individual patient data will allow for analysis of the effects of ARBs in particular patient subgroups and for time-to-event analysis for clinical outcomes. The meta-analysis protocol summarized in this report was written on behalf of the Marfan Treatment Trialists' Collaboration and finalized in late 2012, without foreknowledge of the results of any component trial, and will be made available online (

Original languageEnglish (US)
Pages (from-to)605-612
Number of pages8
JournalAmerican Heart Journal
Issue number5
Publication statusPublished - May 1 2015


ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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