Evidence map›Paper›PMID 36049495›Full record

SynthesisLancet (London, England)2022

Angiotensin receptor blockers and β blockers in Marfan syndrome: an individual patient data meta-analysis of randomised trials.

Alex Pitcher, Enti Spata, Jonathan Emberson, Kelly Davies, Heather Halls, Lisa Holland, Kate Wilson, Christina Reith, Anne H Child, Tim Clayton and 22 more

Registry-linked trialOpen access · hybridAbstract readMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in Lancet (London, England), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07495267 (Nutritional Ketosis as a Novel Therapeutic Strategy to Stabilize Chronic Aortic Dissection in Marfan Syndrome), which is not on this map. Cited by 50 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
50citing papers in PubMed, 1 pooled it
18.7field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT07495267 nanot yet recruitingnot on this mapstarted 2026, after this paper: background citation

Nutritional Ketosis as a Novel Therapeutic Strategy to Stabilize Chronic Aortic Dissection in Marfan Syndrome

TypeinterventionalSponsorWashington University School of MedicineRan2026 to 2028Enrolled15ConditionsMarfan Syndrome, Aortic DissectionArmsKetogenic diet
3 · Its place in the literature

Who cites it

50 citing papers in PubMed, 1 synthesis or guideline pooled it, 104 citations in OpenAlex.

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  12. Journal of vascular surgery cases and innovative techniques · 2026
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  15. Genetic Causes of Thoracic Aortic Aneurysm: A Review.Methodist DeBakey cardiovascular journal · 2026
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

32 authors at 18 institutions in 8 countries.

Alex PitcherThe Heart Centre, John Radcliffe Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, UK; Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
Enti SpataMRC 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.
Jonathan EmbersonMRC 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.
Kelly DaviesMRC 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.
Heather HallsMRC 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.
Lisa HollandMRC 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.
Kate WilsonClinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.
Christina ReithClinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.
Anne H ChildRoyal Brompton and Harefield Hospitals Unit, Guy's and St Thomas' NHS Trust and Department of Surgery and Oncology, Imperial College London, London, UK.
Tim ClaytonClinical Trials Unit, Department of Medical Statistics, London School of Hygiene & Tropical Medicine, London, UK.
Matthew DoddClinical Trials Unit, Department of Medical Statistics, London School of Hygiene & Tropical Medicine, London, UK.
Marcus FlatherFaculty of Medicine and Health Sciences, University of East Anglia, Norwich, UK.
Xu Yu JinThe Heart Centre, John Radcliffe Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
George SandorChildren'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.
Maarten GroeninkAcademic Medical Center, University of Amsterdam, Amsterdam, Netherlands; European Reference Network for Rare Multisystemic Vascular Disease (VASCERN), HTAD Rare Disease Working Group, Amsterdam, The Netherlands.
Barbara MulderAcademic Medical Center, University of Amsterdam, Amsterdam, Netherlands; European Reference Network for Rare Multisystemic Vascular Disease (VASCERN), HTAD Rare Disease Working Group, Amsterdam, The Netherlands.
Julie De BackerCenter 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.
Arturo EvangelistaServei 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.
Alberto FortezaHospital Puerta de Hierro, Majadahonda, Spain.
Gisela Teixido-TuràDepartment 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.
Catherine BoileauUniversité 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 Reference Network for Rare Multisystemic Vascular Disease (VASCERN), HTAD Rare Disease Working Group, Paris, France.
Guillaume JondeauUniversité 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 Reference Network for Rare Multisystemic Vascular Disease (VASCERN), HTAD Rare Disease Working Group, Paris, France.
Olivier MilleronUniversité 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 Reference Network for Rare Multisystemic Vascular Disease (VASCERN), HTAD Rare Disease Working Group, Paris, France.
Ronald V LacroDepartment of Cardiology, Boston Children's Hospital, Boston, MA, USA; Department of Pediatrics, Harvard Medical School, Boston, MA, USA.
Lynn A SleeperDepartment of Cardiology, Boston Children's Hospital, Boston, MA, USA; Department of Pediatrics, Harvard Medical School, Boston, MA, USA.
Hsin-Hui ChiuDepartment of Pediatrics, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan.
Mei-Hwan WuDepartment of Pediatrics and Adult Congenital Heart Center, National Taiwan University Hospital, Taipei, Taiwan.
Stefan NeubauerOxford Centre for Clinical Magnetic Resonance Research, Division of Cardiovascular Medicine, University of Oxford, Oxford, UK.
Hugh WatkinsRadcliffe Department of Medicine, University of Oxford, Oxford, UK.
Hal DietzHoward Hughes Medical Institute and Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Colin BaigentMRC 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.
Marfan Treatment Trialists’ Collaboration
University of Oxford · GBBoston Children's Hospital · USLondon School of Hygiene & Tropical Medicine · GBUniversity of Amsterdam · NLBC Children's Hospital · CACentre for Biomedical Network Research on Rare Diseases · ESGhent University Hospital · BEHôpital Bichat-Claude-Bernard · FRHospital Universitario Puerta de Hierro Majadahonda · ESImperial College London · GBJohn Radcliffe Hospital · GBJohns Hopkins University · USNational Taiwan University Hospital · TWTaipei Tzu Chi Hospital · TWUniversité Claude Bernard Lyon 1 · FRUniversité Paris Cité · FRUniversity of East Anglia · GBVall d'Hebron Institut de Recerca · ES

Funding

British Heart Foundation CH/1992001/6764British Heart Foundation CH/1996001/9454British Heart Foundation RE/13/1/30181Medical Research Council MC_U137686849Medical Research Council MC_UU_00017/3Medical Research Council MC_UU_00017/4Medical Research Council MC_UU_12026/6
6 · The paper itself

Abstract

backgroundAngiotensin receptor blockers (ARBs) and β 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.

methodsIn 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 β 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 β blocker; and indirectly, β 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.

findingsWe 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 β-blocker use (heterogeneity p=0·54). Three trials involving 766 eligible participants compared ARBs with β 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 β-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 β blockers and control was -0·09 (95% CI -0·18 to 0·00; p=0·042).

interpretationIn 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 β blocker. The effects of β blockers were similar to those of ARBs. 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.

fundingMarfan Foundation, the Oxford British Heart Foundation Centre for Research Excellence, and the UK Medical Research Council.

Indexed as

Marfan SyndromeAdrenergic beta-AntagonistsAngiotensin-Converting Enzyme InhibitorsAngiotensin Receptor AntagonistsAortaHumansRandomized Controlled Trials as TopicAdrenergic beta-AntagonistsAngiotensin-Converting Enzyme InhibitorsAngiotensin Receptor Antagonists

Identifiers

PMID36049495
PMCPMC7613630
OpenAlexW4293797820

What OpenQuestion holds

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LicenceCC BY
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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.