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. 2015 Apr 24:350:h1857.
doi: 10.1136/bmj.h1857.

Comparative risk of gastrointestinal bleeding with dabigatran, rivaroxaban, and warfarin: population based cohort study

Neena S Abraham  1 , Sonal Singh  2 , G Caleb Alexander  2 , Herbert Heien  3 , Lindsey R Haas  3 , William Crown  4 , Nilay D Shah  5
Affiliations

Comparative risk of gastrointestinal bleeding with dabigatran, rivaroxaban, and warfarin: population based cohort study

Neena S Abraham et al. BMJ. .

Abstract

Objective: To determine the real world risk of gastrointestinal bleeding associated with the use of the novel oral anticoagulants dabigatran and rivaroxaban compared with warfarin.

Design: Retrospective, propensity matched cohort study.

Setting: Optum Labs Data Warehouse, a large database including administrative claims data on privately insured and Medicare Advantage enrollees.

Participants: New users of dabigatran, rivaroxaban, and warfarin from 1 November 2010 to 30 September 2013.

Main outcome measures: Incidence rates (events/100 patient years) and propensity score matched Cox proportional hazards models were used to estimate rates of total gastrointestinal bleeds, upper gastrointestinal bleeds, and lower gastrointestinal bleeds for the novel oral anticoagulants compared with warfarin in patients with and without atrial fibrillation. Heterogeneity of treatment effect related to age was examined using a marginal effects model.

Results: The incidence of gastrointestinal bleeding associated with dabigatran was 2.29 (95% confidence interval 1.88 to 2.79) per 100 patient years and that associated with warfarin was 2.87 (2.41 to 3.41) per 100 patient years in patients with atrial fibrillation. In non-atrial fibrillation patients, the incidence of gastrointestinal bleeding was 4.10 (2.47 to 6.80) per 100 patient years with dabigatran and 3.71 (2.16 to 6.40) per 100 patient years with warfarin. With rivaroxaban, 2.84 (2.30 to 3.52) gastrointestinal bleeding events per 100 patient years occurred in atrial fibrillation patients (warfarin 3.06 (2.49 to 3.77)/100 patient years) and 1.66 (1.23 to 2.24) per 100 patient years in non-atrial fibrillation patients (warfarin 1.57 (1.25 to 1.99)/100 patient years). In propensity score matched models, the risk of gastrointestinal bleeding with novel oral anticoagulants was similar to that with warfarin in atrial fibrillation patients (dabigatran v warfarin, hazard ratio 0.79 (0.61 to 1.03); rivaroxaban v warfarin, 0.93 (0.69 to 1.25)) and in non-AF patients (dabigatran v warfarin, hazard ratio 1.14 (0.54 to 2.39); rivaroxaban v warfarin, 0.89 (0.60 to 1.32)). The risk of gastrointestinal bleeding increased after age 65, such that by age 76 the risk exceeded that with warfarin among atrial fibrillation patients taking dabigatran (hazard ratio 2.49 (1.61 to 3.83)) and patients with and without atrial fibrillation taking rivaroxaban (2.91 (1.65 to 4.81) and 4.58 (2.40 to 8.72), respectively).

Conclusions: The risk of gastrointestinal bleeding related to novel oral anticoagulants was similar to that for warfarin. Caution should be used when prescribing novel oral anticoagulants to older people, particularly those over 75 years of age.

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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 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 study
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Fig 2 Dabigatran versus warfarin in patients with atrial fibrillation: treatment effect by age
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Fig 3 Rivaroxaban versus warfarin patients with atrial fibrillation: treatment effect by age
See this image and copyright information in PMC

Comment in

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