Risk of gastrointestinal bleeding associated with oral anticoagulants: population based retrospective cohort study
BMJ 2015; 350 doi: https://doi.org/10.1136/bmj.h1585 (Published 24 April 2015) Cite this as: BMJ 2015;350:h1585
- Hsien-Yen Chang, assistant scientist1,
- Meijia Zhou, master student2,
- Wenze Tang, master student3,
- G Caleb Alexander, associate professor24,
- Sonal Singh, assistant professor24
- 1Department of Health Policy and Management, Center for Drug Safety and Effectiveness, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA
- 2Department of Epidemiology, Center for Drug Safety and Effectiveness, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA
- 3Department of Epidemiology and Biostatistics, Milken Institute School of Public Health, The George Washington University, Washington, DC 20052, USA
- 4Division of General Internal Medicine, Johns Hopkins Medicine, Baltimore, MD 21205, USA
- Correspondence to: H Chang hchang24{at}jhmi.edu
- Accepted 11 February 2015
Abstract
Objectives To determine the real world safety of dabigatran or rivaroxaban compared with warfarin in terms of gastrointestinal bleeding.
Design Retrospective cohort study.
Setting Large administrative database of commercially insured people in United States from 1 October 2010 through 31 March 2012.
Participants Enrollees with a prescription of warfarin, dabigatran, or rivaroxaban between 1 October 2010 and 31 March 2012, who were aged 18 years or older, had continuous enrollment and no oral anticoagulant use during the six months before the entry date, with known age and sex, and with no gastrointestinal bleeding for at least six months before the cohort entry date. The final study sample of 46 163 patients included 4907 using dabigatran, 1649 using rivaroxaban, and 39 607 using warfarin.
Main outcome measure Time to gastrointestinal bleeding. Hazard ratios were derived from Cox proportional hazard models with propensity score weighting and robust estimates of errors.
Results Dabigatran users tended to be older (dabigatran v rivaroxaban v warfarin: 62.0 v 57.6 v 57.4 years) and more likely to be male (69% v 49% v 53%). The rate of gastrointestinal bleeding was highest among dabigatran users and lowest among rivaroxaban users (dabigatran v rivaroxaban v warfarin: 9.01 v 3.41 v 7.02 cases per 100 person years). After adjustment for potentially confounding covariates, there was no evidence of a statistically significant difference in the risk of gastrointestinal bleeding between dabigatran and warfarin users (adjusted hazard ratio 1.21, 95% confidence interval 0.96 to 1.53) or between rivaroxaban and warfarin users (0.98, 0.36 to 2.69).
Conclusions Although rates of gastrointestinal bleeding seem to be similar in this commercially insured sample of adults in the United States, we cannot rule out as much as a 50% increase in the risk of gastrointestinal bleeding with dabigatran compared with warfarin or a more than twofold higher risk of bleeding with rivaroxaban compared with warfarin.
Footnotes
The statements, findings, conclusions, views, and opinions contained and expressed in this article are based in part on data obtained under license from the following IMS Health Incorporated information service(s): IMS Health LifeLink LRx Database (2007-13), IMS Health Incorporated. All rights reserved. The statements, findings, conclusions, views, and opinions contained and expressed herein are not necessarily those of IMS Health Incorporated or any of its affiliated or subsidiary entities.
Contributors: HC designed the study, managed data, did analyses, and drafted the manuscript. MZ managed data and drafted the manuscript. WT did analyses and drafted the manuscript. GCA provided critical comments and revised the manuscript. SS designed the study, secured data, and drafted the manuscript. All authors had full access to all of the data (including statistical reports and tables) in the study and can take responsibility for the integrity of the data and the accuracy of the data analysis. All authors approved of the final manuscript. HC and SS are the guarantors.
Funding: GCA is supported by the National Heart, Lung and Blood Institute (R01 HL107345). The funding source had no role in the design and conduct of the study, the analysis or interpretation of the data, or the preparation or final approval of the manuscript before publication.
Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: GCA is supported by the National Heart, Lung and Blood Institute (R01 HL107345); GCA is chair of the FDA’s Peripheral and Central Nervous System Advisory Committee, serves as a paid consultant to IMS Health, and serves on an IMS Health scientific advisory board; this arrangement has been reviewed and approved by Johns Hopkins University in accordance with its conflict of interest policies; no other relationships or activities that could appear to have influenced the submitted work.
Ethical approval: The data source included de-identified information, and this project was deemed not to be human subjects research by the institutional review board of the Johns Hopkins Bloomberg School of Public Health; ethics review board approval for such studies is not required.
Data sharing: No additional data available.
Transparency: HC and SS affirm 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 (and, if relevant, registered) have been explained.
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