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Angiotensin receptor blockers and ß blockers in Marfan syndrome: an individual patient data meta-analysis of randomised trials.
Pitcher, Alex; Spata, Enti; Emberson, Jonathan; Davies, Kelly; Halls, Heather; Holland, Lisa; Wilson, Kate; Reith, Christina; Child, Anne H; Clayton, Tim; Dodd, Matthew; Flather, Marcus; Jin, Xu Yu; Sandor, George; Groenink, Maarten; Mulder, Barbara; De Backer, Julie; Evangelista, Arturo; Forteza, Alberto; Teixido-Turà, Gisela; Boileau, Catherine; Jondeau, Guillaume; Milleron, Olivier; Lacro, Ronald V; Sleeper, Lynn A; Chiu, Hsin-Hui; Wu, Mei-Hwan; Neubauer, Stefan; Watkins, Hugh; Dietz, Hal; Baigent, Colin.
Afiliação
  • Pitcher A; The Heart Centre, John Radcliffe Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, UK; Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
  • Spata E; MRC Population Health Research Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK; Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.
  • Emberson J; MRC Population Health Research Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK; Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.
  • Davies K; MRC Population Health Research Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK; Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.
  • Halls H; MRC Population Health Research Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK; Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.
  • Holland L; MRC Population Health Research Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK; Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.
  • Wilson K; Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.
  • Reith C; Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.
  • Child AH; Royal Brompton and Harefield Hospitals Unit, Guy's and St Thomas' NHS Trust and Department of Surgery and Oncology, Imperial College London, London, UK.
  • Clayton T; Clinical Trials Unit, Department of Medical Statistics, London School of Hygiene & Tropical Medicine, London, UK.
  • Dodd M; Clinical Trials Unit, Department of Medical Statistics, London School of Hygiene & Tropical Medicine, London, UK.
  • Flather M; Faculty of Medicine and Health Sciences, University of East Anglia, Norwich, UK.
  • Jin XY; The Heart Centre, John Radcliffe Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
  • Sandor G; Children's Heart Centre, British Columbia's Children's Hospital, Vancouver, BC, Canada; Department of Paediatrics, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada.
  • Groenink M; Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands; European Reference Network for Rare Multisystemic Vascular Disease (VASCERN), HTAD Rare Disease Working Group, Amsterdam, The Netherlands.
  • Mulder B; Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands; European Reference Network for Rare Multisystemic Vascular Disease (VASCERN), HTAD Rare Disease Working Group, Amsterdam, The Netherlands.
  • De Backer J; Center for Medical Genetics and Department of Cardiology, Ghent University Hospital, Ghent, Belgium; European Reference Network for Rare Multisystemic Vascular Disease (VASCERN), HTAD Rare Disease Working Group, Ghent, Belgium.
  • Evangelista A; Servei de Cardiologia, Hospital Universitari Vall d'Hebron, Barcelona, Spain; European Reference Network for Rare Multisystemic Vascular Disease (VASCERN), HTAD Rare Disease Working Group, Barcelona, Spain.
  • Forteza A; Hospital Puerta de Hierro, Majadahonda, Spain.
  • Teixido-Turà G; Department of Cardiology, Hospital Universitari Vall d'Hebron, CIBER-CV, Vall d'Hebron institut de Recerca, Universitat Autònoma de Barcelona, Barcelona, Spain; European Reference Network for Rare Multisystemic Vascular Disease (VASCERN), HTAD Rare Disease Working Group, Barcelona, Spain.
  • Boileau C; Université Paris Cité and Université Sorbonne Paris Nord, Inserm U1148, LVTS, F-75018 Paris, France; Service de Cardiologie, AP-HP Hôpital Bichat-Claude Bernard, F-75018, Paris, France; CRMR Syndrome de Marfan et apparentés. AP-HP Hôpital Bichat-Claude Bernard, F-75018, Paris, France; European Refer
  • Jondeau G; Université Paris Cité and Université Sorbonne Paris Nord, Inserm U1148, LVTS, F-75018 Paris, France; Service de Cardiologie, AP-HP Hôpital Bichat-Claude Bernard, F-75018, Paris, France; CRMR Syndrome de Marfan et apparentés. AP-HP Hôpital Bichat-Claude Bernard, F-75018, Paris, France; European Refer
  • Milleron O; Université Paris Cité and Université Sorbonne Paris Nord, Inserm U1148, LVTS, F-75018 Paris, France; Service de Cardiologie, AP-HP Hôpital Bichat-Claude Bernard, F-75018, Paris, France; CRMR Syndrome de Marfan et apparentés. AP-HP Hôpital Bichat-Claude Bernard, F-75018, Paris, France; European Refer
  • Lacro RV; Department of Cardiology, Boston Children's Hospital, Boston, MA, USA; Department of Pediatrics, Harvard Medical School, Boston, MA, USA.
  • Sleeper LA; Department of Cardiology, Boston Children's Hospital, Boston, MA, USA; Department of Pediatrics, Harvard Medical School, Boston, MA, USA.
  • Chiu HH; Department of Pediatrics, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan.
  • Wu MH; Department of Pediatrics and Adult Congenital Heart Center, National Taiwan University Hospital, Taipei, Taiwan.
  • Neubauer S; Oxford Centre for Clinical Magnetic Resonance Research, Division of Cardiovascular Medicine, University of Oxford, Oxford, UK.
  • Watkins H; Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
  • Dietz H; Howard Hughes Medical Institute and Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Baigent C; MRC Population Health Research Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK; Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK. Electronic address: colin.baigent@ndph.ox.ac.uk.
Lancet ; 400(10355): 822-831, 2022 09 10.
Article em En | MEDLINE | ID: mdl-36049495
BACKGROUND: Angiotensin receptor blockers (ARBs) and ß blockers are widely used in the treatment of Marfan syndrome to try to reduce the rate of progressive aortic root enlargement characteristic of this condition, but their separate and joint effects are uncertain. We aimed to determine these effects in a collaborative individual patient data meta-analysis of randomised trials of these treatments. METHODS: In this meta-analysis, we identified relevant trials of patients with Marfan syndrome by systematically searching MEDLINE, Embase, and CENTRAL from database inception to Nov 2, 2021. Trials were eligible if they involved a randomised comparison of an ARB versus control or an ARB versus ß blocker. We used individual patient data from patients with no prior aortic surgery to estimate the effects of: ARB versus control (placebo or open control); ARB versus ß blocker; and indirectly, ß blocker versus control. The primary endpoint was the annual rate of change of body surface area-adjusted aortic root dimension Z score, measured at the sinuses of Valsalva. FINDINGS: We identified ten potentially eligible trials including 1836 patients from our search, from which seven trials and 1442 patients were eligible for inclusion in our main analyses. Four trials involving 676 eligible participants compared ARB with control. During a median follow-up of 3 years, allocation to ARB approximately halved the annual rate of change in the aortic root Z score (mean annual increase 0·07 [SE 0·02] ARB vs 0·13 [SE 0·02] control; absolute difference -0·07 [95% CI -0·12 to -0·01]; p=0·012). Prespecified secondary subgroup analyses showed that the effects of ARB were particularly large in those with pathogenic variants in fibrillin-1, compared with those without such variants (heterogeneity p=0·0050), and there was no evidence to suggest that the effect of ARB varied with ß-blocker use (heterogeneity p=0·54). Three trials involving 766 eligible participants compared ARBs with ß blockers. During a median follow-up of 3 years, the annual change in the aortic root Z score was similar in the two groups (annual increase -0·08 [SE 0·03] in ARB groups vs -0·11 [SE 0·02] in ß-blocker groups; absolute difference 0·03 [95% CI -0·05 to 0·10]; p=0·48). Thus, indirectly, the difference in the annual change in the aortic root Z score between ß blockers and control was -0·09 (95% CI -0·18 to 0·00; p=0·042). INTERPRETATION: In people with Marfan syndrome and no previous aortic surgery, ARBs reduced the rate of increase of the aortic root Z score by about one half, including among those taking a ß blocker. The effects of ß blockers were similar to those of ARBs. Assuming additivity, combination therapy with both ARBs and ß 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. FUNDING: Marfan Foundation, the Oxford British Heart Foundation Centre for Research Excellence, and the UK Medical Research Council.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Clinical_trials / Prognostic_studies / Systematic_reviews Limite: Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Clinical_trials / Prognostic_studies / Systematic_reviews Limite: Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article