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Original research
Risk of acute arterial events associated with treatment of inflammatory bowel diseases: nationwide French cohort study
  1. Julien Kirchgesner1,2,
  2. Nynne Nyboe Andersen3,4,
  3. Fabrice Carrat2,5,
  4. Tine Jess3,
  5. Laurent Beaugerie1,2
  6. BERENICE study group
    1. 1 Department of Gastroenterology, Hôpital Saint-Antoine, Assistance Publique—Hôpitaux de Paris, Paris, France
    2. 2 INSERM, Institut Pierre Louis d’Epidémiologie et de Santé Publique, Sorbonne Universite, Paris, France
    3. 3 Department of Epidemiology Research, Statens Serum Institut, Kobenhavn, Denmark
    4. 4 Department of Gastroenterology, Zealand University Hospital Koge, Koge, Denmark
    5. 5 Department of Public Health, Hôpital Saint-Antoine, Assistance Publique—Hôpitaux de Paris, Paris, France
    1. Correspondence to Julien Kirchgesner, Service de Gastroentérologie et Nutrition, Hôpital Saint-Antoine, Assistance Publique - Hôpitaux de Paris, 184 rue du faubourg Saint-Antoine, Paris 75012, France; julien.kirchgesner{at}gmx.com

    Abstract

    Objective Patients with IBD are at increased risk of acute arterial events. Antitumour necrosis factor (TNF) agents and thiopurines may, via their anti-inflammatory properties, lower the risk of acute arterial events. The aim of this study was to assess the impact of thiopurines and anti-TNFs on the risk of acute arterial events in patients with IBD.

    Design Patients aged 18 years or older and affiliated to the French national health insurance with a diagnosis of IBD were followed up from 1 April 2010 until 31 December 2014. The risks of acute arterial events (including ischaemic heart disease, cerebrovascular disease and peripheral artery disease) were compared between thiopurines and anti-TNFs exposed and unexposed patients with marginal structural Cox proportional hazard models adjusting for baseline and time-varying demographics, medications, traditional cardiovascular risk factors, comorbidities and IBD disease activity.

    Results Among 177 827 patients with IBD (96 111 (54%) women, mean age at cohort entry 46.2 years (SD 16.3), 90 205 (50.7%) with Crohn’s disease (CD)), 4145 incident acute arterial events occurred (incidence rates: 5.4 per 1000 person-years). Compared with unexposed patients, exposure to anti-TNFs (HR 0.79, 95% CI 0.66 to 0.95), but not to thiopurines (HR 0.93, 95% CI 0.82 to 1.05), was associated with a decreased risk of acute arterial events. The magnitude in risk reduction was highest in men with CD exposed to anti-TNFs (HR 0.54, 95% CI 0.40 to 0.72).

    Conclusion Exposure to anti-TNFs is associated with a decreased risk of acute arterial events in patients with IBD, particularly in men with CD.

    • inflammatory bowel disease
    • cardiovascular disease
    • ischeamic heart disease
    • cerebrovascular disease
    • peripheral arterial disease
    • thiopurines
    • anti-TNFs

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    Footnotes

    • Collaborators Collaborators of the BERENICE study group are the following: Laurent Beaugerie, Anne-Marie Bouvier, Anne Buisson, Franck Carbonnel, Fabrice Carrat, Jacques Cosnes, Corinne Gower-Rousseau, Julien Kirchgesner, Alain Olympie, Laurent Peyrin-Biroulet, Jean-François Rahier, Frank Ruemmele, Michael Schwarzinger, Tabassome Simon, Yazdan Yazdanpanah.

    • Contributors JK: study concept and design, acquisition of data, analysis and interpretation of data, drafting of the manuscript, critical revision of the manuscript for important intellectual content and statistical analysis. NNA: study concept and design, analysis and interpretation of data, and critical revision of the manuscript for important intellectual content. FC: analysis and interpretation of data and critical revision of the manuscript for important intellectual content.TJ: study concept and design, analysis and interpretation of data, and critical revision of the manuscript for important intellectual content. LB: study concept and design, analysis and interpretation of data, drafting of the manuscript and study supervision.

    • Funding The BERENICE project is supported by grants from the French National Agency for Medicines and Health Products Safety (Agence Nationale de Sécurité du Médicament).

    • Competing interests LB has received consulting fees from Abbott; lecture fees from Abbott, Abbvie, MSD, Ferring Pharmaceuticals and Janssen; and research support from Abbott, Biocodex and Ferring Pharmaceuticals. JK, NNA, FC and TJ disclose no conflicts.

    • Patient consent for publication Not required.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Data availability statement All data relevant to the study are included in the article or uploaded as supplementary information.