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 Pitcher¹, Jonathan Emberson², Ronald V Lacro³, Lynn A Sleeper⁴, Mario Stylianou⁵, Lynn Mahony⁶, Gail D Pearson⁵, Maarten Groenink⁷, Barbara J Mulder⁷, Aeilko H Zwinderman⁷, Julie De Backer⁸, Anne M De Paepe⁹, Eloisa Arbustini¹⁰, Guliz Erdem¹¹, Xu Yu Jin¹², Marcus D Flather¹³, Michael J Mullen¹⁴, Anne H Child¹⁵, Alberto Forteza¹⁶, Arturo Evangelista¹⁷, Hsin-Hui Chiu¹⁸, Mei-Hwan Wu¹⁹, George Sandor²⁰, Ami B Bhatt²¹, Mark A Creager²², Richard B Devereux²³, Bart Loeys²⁴, J Colin Forfar¹², Stefan Neubauer²⁵, Hugh Watkins²⁶, Catherine Boileau²⁷, Guillaume Jondeau²⁸, Harry C Dietz²⁹, Colin Baigent²

Affiliations

¹ Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK. Electronic address: alex.pitcher@cardiov.ox.ac.uk.
² Clinical Trial Service Unit & Epidemiological Studies Unit, University of Oxford, Oxford, UK.
³ Children's Hospital Boston and Harvard Medical School, Boston, MA.
⁴ New England Research Institutes, Watertown, MA.
⁵ National Heart, Lung, and Blood Institute, NIH, Bethesda, MD.
⁶ University of Texas Southwestern Medical Center, Dallas, TX.
⁷ Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
⁸ Center for Medical Genetics and Department of Cardiology, University Hospital Ghent, Ghent, Belgium.
⁹ Center for Medical Genetics, University Hospital Ghent, Ghent, Belgium.
¹⁰ Centre for Inherited Cardiovascular Diseases, IRCCS Foundation, San Matteo Hospital, Pavia, Italy.
¹¹ Clinical Trials and Evaluation Unit, Royal Brompton & Harefield NHS Trust, London, UK.
¹² John Radcliffe Hospital, Oxford, UK.
¹³ Faculty of Medicine and Health Sciences, University of East Anglia, Norwich, UK.
¹⁴ UCL Institute of Cardiovascular Science, The Heart Hospital, London, UK.
¹⁵ Department of Cardiac and Vascular Sciences, St George's Hospital, University of London, London, UK.
¹⁶ Hospital Universitario 12 de Octubre, Madrid, Spain.
¹⁷ Marfan Sydrome Unit, Department of Cardiology, Hospital Vall d'Hebron, Barcelona, Spain.
¹⁸ Department of Pediatrics and Adult Congenital Heart Center, Taipei Medical University Hospital, Taipei, Taiwan.
¹⁹ Department of Pediatrics and Adult Congenital Heart Center, National Taiwan University Hospital, Taipei, Taiwan.
²⁰ Children's Heart Centre, British Columbia's Children's Hospital, Vancouver, British Columbia, Canada.
²¹ Massachusetts General Hospital, Boston, MA.
²² Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
²³ Weill Cornell Medical College and New York-Presbyterian Hospital, New York, NY.
²⁴ Center for Medical Genetics, Faculty of Medicine and Health Sciences, University of Antwerp and Antwerp University Hospital, Antwerp, Belgium.
²⁵ Oxford Centre for Clinical Magnetic Resonance Research, Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
²⁶ Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
²⁷ Inserm LVTS U1148, Departement de Génétique, Hôpital Xavier Bichat-Claude Bernard, Paris, France.
²⁸ Centre National de Référence pour le syndrome de Marfan et apparentés, INSERM LVTS U1148, Service de Cardiologie, AP-HP Hôpital Bichat, Paris, France.
²⁹ McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, and the Howard Hughes Medical Institute, Baltimore, MD.

PMID: 25965707
PMCID: PMC4441104
DOI: 10.1016/j.ahj.2015.01.011

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 et al. Am Heart J. 2015 May.

. 2015 May;169(5):605-12.

doi: 10.1016/j.ahj.2015.01.011. Epub 2015 Feb 12.

Authors

Affiliations

¹ Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK. Electronic address: alex.pitcher@cardiov.ox.ac.uk.
² Clinical Trial Service Unit & Epidemiological Studies Unit, University of Oxford, Oxford, UK.
³ Children's Hospital Boston and Harvard Medical School, Boston, MA.
⁴ New England Research Institutes, Watertown, MA.
⁵ National Heart, Lung, and Blood Institute, NIH, Bethesda, MD.
⁶ University of Texas Southwestern Medical Center, Dallas, TX.
⁷ Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
⁸ Center for Medical Genetics and Department of Cardiology, University Hospital Ghent, Ghent, Belgium.
⁹ Center for Medical Genetics, University Hospital Ghent, Ghent, Belgium.
¹⁰ Centre for Inherited Cardiovascular Diseases, IRCCS Foundation, San Matteo Hospital, Pavia, Italy.
¹¹ Clinical Trials and Evaluation Unit, Royal Brompton & Harefield NHS Trust, London, UK.
¹² John Radcliffe Hospital, Oxford, UK.
¹³ Faculty of Medicine and Health Sciences, University of East Anglia, Norwich, UK.
¹⁴ UCL Institute of Cardiovascular Science, The Heart Hospital, London, UK.
¹⁵ Department of Cardiac and Vascular Sciences, St George's Hospital, University of London, London, UK.
¹⁶ Hospital Universitario 12 de Octubre, Madrid, Spain.
¹⁷ Marfan Sydrome Unit, Department of Cardiology, Hospital Vall d'Hebron, Barcelona, Spain.
¹⁸ Department of Pediatrics and Adult Congenital Heart Center, Taipei Medical University Hospital, Taipei, Taiwan.
¹⁹ Department of Pediatrics and Adult Congenital Heart Center, National Taiwan University Hospital, Taipei, Taiwan.
²⁰ Children's Heart Centre, British Columbia's Children's Hospital, Vancouver, British Columbia, Canada.
²¹ Massachusetts General Hospital, Boston, MA.
²² Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
²³ Weill Cornell Medical College and New York-Presbyterian Hospital, New York, NY.
²⁴ Center for Medical Genetics, Faculty of Medicine and Health Sciences, University of Antwerp and Antwerp University Hospital, Antwerp, Belgium.
²⁵ Oxford Centre for Clinical Magnetic Resonance Research, Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
²⁶ Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
²⁷ Inserm LVTS U1148, Departement de Génétique, Hôpital Xavier Bichat-Claude Bernard, Paris, France.
²⁸ Centre National de Référence pour le syndrome de Marfan et apparentés, INSERM LVTS U1148, Service de Cardiologie, AP-HP Hôpital Bichat, Paris, France.
²⁹ McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, and the Howard Hughes Medical Institute, Baltimore, MD.

PMID: 25965707
PMCID: PMC4441104
DOI: 10.1016/j.ahj.2015.01.011

Abstract

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 (http://www.ctsu.ox.ac.uk/research/meta-trials).

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References

1. McKusick V.A. The cardiovascular aspects of Marfan's syndrome: a heritable disorder of connective tissue. Circulation. 1955;11(3):321–342. - PubMed
1. De Backer J. The expanding cardiovascular phenotype of Marfan syndrome. Eur J Echocardiogr. 2009;10(2):213–215. - PubMed
1. De Backer J. Cardiovascular characteristics in Marfan syndrome and their relation to the genotype. Verh K Acad Geneeskd Belg. 2009;71(6):335–371. - PubMed
1. Judge D.P., Rouf R., Habashi J. Mitral valve disease in Marfan syndrome and related disorders. J Cardiovasc Transl Res. 2011;4(6):741–747. - PubMed
1. Alpendurada F., Wong J., Kiotsekoglou A. Evidence for Marfan cardiomyopathy. Eur J Heart Fail. 2010;12(10):1085–1091. - PubMed

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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

Affiliations

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

Authors

Affiliations

Abstract

References

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources