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Comparative Study
. 2015 Apr 24:350:h1585.
doi: 10.1136/bmj.h1585.

Risk of gastrointestinal bleeding associated with oral anticoagulants: population based retrospective cohort study

Hsien-Yen Chang  1 , Meijia Zhou  2 , Wenze Tang  3 , G Caleb Alexander  4 , Sonal Singh  4
Affiliations
Comparative Study

Risk of gastrointestinal bleeding associated with oral anticoagulants: population based retrospective cohort study

Hsien-Yen Chang et al. BMJ. .

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.

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Conflict of interest statement

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.

Figures

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Fig 1 Flow chart of sample size
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Fig 2 Survival function and number of patients at risk over time by drug use
See this image and copyright information in PMC

Comment in

References

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    1. Connolly SJ, Ezekowitz MD, Yusuf S, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009;361:1139-51. - PubMed
    1. Patel MR, Mahaffey KW, Garg J, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 2011;365:883-91. - PubMed

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