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Stroke and recurrent haemorrhage associated with antithrombotic treatment after gastrointestinal bleeding in patients with atrial fibrillation: nationwide cohort study

BMJ 2015; 351 doi: https://doi.org/10.1136/bmj.h5876 (Published 16 November 2015) Cite this as: BMJ 2015;351:h5876
  1. Laila Staerk, research fellow12,
  2. Gregory Y H Lip, professor2,
  3. Jonas B Olesen, senior research fellow1,
  4. Emil L Fosbøl, senior research fellow3,
  5. Jannik L Pallisgaard, research fellow1,
  6. Anders N Bonde, research fellow1,
  7. Anna Gundlund, research fellow1,
  8. Tommi B Lindhardt, senior research fellow1,
  9. Morten L Hansen, senior research fellow3,
  10. Christian Torp-Pedersen, professor4,
  11. Gunnar H Gislason, research director and professor1567
  1. 1Department of Cardiology, Copenhagen University Hospital Herlev, and Gentofte, Kildegaardsvej 28, 2900 Hellerup, Denmark
  2. 2University of Birmingham Centre for Cardiovascular Sciences, Birmingham City Hospital, Birmingham UK
  3. 3Department of Cardiology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark
  4. 4Institute of Health, Science and Technology, Aalborg University, Aalborg, Denmark
  5. 5Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
  6. 6National Institute of Public Health, University of Southern Denmark, Copenhagen, Denmark
  7. 7Danish Heart Foundation, Copenhagen, Denmark
  1. Correspondence to: L Staerk Lailastaerk{at}gmail.com
  • Accepted 12 October 2015

Abstract

Study question What are the risks of all cause mortality, thromboembolism, major bleeding, and recurrent gastrointestinal bleeding associated with restarting antithrombotic treatment after gastrointestinal bleeding in patients with atrial fibrillation?

Methods This Danish cohort study (1996-2012) included all patients with atrial fibrillation discharged from hospital after gastrointestinal bleeding while receiving antithrombotic treatment. Restarted treatment regimens were single or combined antithrombotic drugs with oral anticoagulation and antiplatelets. Follow-up started 90 days after discharge to avoid confounding from use of previously prescribed drugs on discharge. Risks of all cause mortality, thromboembolism, major bleeding, and recurrent gastrointestinal bleeding were estimated with competing risks models and time dependent multiple Cox regression models.

Study answer and limitations 4602 patients (mean age 78 years) were included. Within two years, 39.9% (95% confidence interval 38.4% to 41.3%, n=1745) of the patients had died, 12.0% (11.0% to 13.0%, n=526) had experienced thromboembolism, 17.7% (16.5% to 18.8%, n=788) major bleeding, and 12.1% (11.1% to 13.1%, n=546) recurrent gastrointestinal bleeding. 27.1% (n=924) of patients did not resume antithrombotic treatment. Compared with non-resumption of treatment, a reduced risk of all cause mortality was found in association with restart of oral anticoagulation (hazard ratio 0.39, 95% confidence interval 0.34 to 0.46), an antiplatelet agent (0.76, 0.68 to 0.86), and oral anticoagulation plus an antiplatelet agent (0.41, 0.32 to 0.52), and a reduced risk of thromboembolism was found in association with restart of oral anticoagulation (0.41, 0.31 to 0.54), an antiplatelet agent (0.76, 0.61 to 0.95), and oral anticoagulation plus an antiplatelet agent (0.54, 0.36 to 0.82). Restarting oral anticoagulation alone was the only regimen with an increased risk of major bleeding (1.37, 1.06 to 1.77) compared with non-resumption of treatment; however, the difference in risk of recurrent gastrointestinal bleeding was not significant between patients who restarted an antithrombotic treatment regimen and those who did not resume treatment.

What this study adds Among patients with atrial fibrillation who experience gastrointestinal bleeding while receiving antithrombotic treatment; subsequent restart of oral anticoagulation alone was associated with better outcomes for all cause mortality and thromboembolism compared with patients who did not resume treatment. This was despite an increased longitudinal associated risk of bleeding.

Funding, competing interests, data sharing This study was supported by a grant from Boehringer-Ingelheim. Competing interests are available in the full paper on bmj.com. The authors have no additional data to share.

Footnotes

  • Contributors: GYHL and GHG are joint senior authors. LS, GYHL, JBO, and GHG conceived and designed the study and carried out the statistical analysis. GYHL and GHG provided administrative, technical, or material support. GYHL, JBO, ELF, JLP, AG, ANB, TBL, CT-P, and GHG supervised the study. LS drafted the manuscript. All authors acquired, analysed, or interpreted the data, critically revised the manuscript for important intellectual content, and gave final approval of the version for publication. LS and GHG had full access to all of the data in the study and take responsibility for the integrity of the data, for the accuracy of the data analysis, and that the manuscript is an honest, accurate, and transparent account of the study. LS is the guarantor.

  • Funding: This study was supported by a grant from Boehringer-Ingelheim. The sponsor had no influence on the study design, interpretation of results, or the decision to submit the manuscript for publication.

  • Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: GYHL has served as a consultant for Bayer, Astellas, Merck, Sanofi, Pfizer/Bristol Meyers Squibb, Daiichi-Sankyo, Biotronik, Medtronic, Portola, and Boehringer Ingelheim and has been on the speakers’ bureau for Bayer, Pfizer/Bristol Meyers Squibb, Boehringer Ingelheim, Daiichi-Sankyo, Medtronic, and Sanofi Aventis. JBO has received speaker fees from Bristol Myers Squibb and Boehringer Ingelheim and funding for research from the Lundbeck Foundation, Bristol-Myers Squibb, and the Capital Region of Denmark, Foundation for Health Research. ELF was previously supported by a project specific research grant from Janssen Pharmaceuticals and has received funding for research from the Lundbeck Foundation and Bristol-Myers Squibb. AG has received funding from Bristol-Myers Squibb. GHG has received research grants from Pfizer/Bristol Meyers Squibb, Bayer, Boehringer-Ingelheim, and AstraZeneca and speaker fees from AstraZeneca, Pfizer, and Sanofi Aventis. All authors state independence from the funders.

  • Ethical approval: Retrospective registry based studies do not require approval from the research ethics committee system in Denmark; data were structured with no possibility for individual patient identification but allowed linkage between registries. The Danish Data Protection Agency had approved use of data for the study (reference No 2007-58-0015/GEH-2014-012 I-Suite No 02720).

  • Data sharing: No additional data available. Details of statistical analysis are available from the corresponding author (Lailastaerk{at}gmail.com) on request.

  • Transparency: The lead author (LS) affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned have been explained.

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