Gastroenterology

Gastroenterology

Volume 152, Issue 5, April 2017, Pages 1014-1022.e1
Gastroenterology

Original Research
Full Report: Clinical—Alimentary Tract
Gastrointestinal Safety of Direct Oral Anticoagulants: A Large Population-Based Study

https://doi.org/10.1053/j.gastro.2016.12.018Get rights and content

Background & Aims

Direct oral anticoagulant (DOAC) agents increase the risk of gastrointestinal (GI) bleeding. We investigated which DOAC had the most favorable GI safety profile and compared differences among these drugs in age-related risk of GI bleeding.

Methods

We conducted a retrospective, propensity-matched study using administrative claims data from the OptumLabs Data Warehouse of privately insured individuals and Medicare Advantage enrollees. We created 3 propensity-matched cohorts of patients with non-valvular atrial fibrillation with incident exposure to dabigatran, rivaroxaban, or apixaban from October 1, 2010 through February 28, 2015. We compared data on rivaroxaban vs dabigatran for 31,574 patients, data on apixaban vs dabigatran for 13,084 patients, and data on apixaban vs rivaroxaban for 13,130 patients. Cox proportional hazards models, stratified by age, were used to estimate rates of total GI bleeding.

Results

Baseline characteristics were well balanced among sub-cohorts. GI bleeding occurred more frequently in patients given rivaroxaban than dabigatran (hazard ratio [HR], 1.20; 95% confidence interval [CI], 1.00−1.45). Apixaban was associated with a lower risk of GI bleeding than dabigatran (HR, 0.39; 95% CI, 0.27−0.58; P < .001) or rivaroxaban (HR, 0.33; 95% CI, 0.22−0.49; P < .001). Rates of events for all DOACs increased among patients 75 years or older. Apixaban had a lower risk of association with GI bleeding in the very elderly than dabigatran (HR, 0.45; 95% CI, 0.29−0.71) or rivaroxaban (HR, 0.39; 95% CI, 0.25−0.61). Median times to GI bleeding were <90 days for apixaban and rivaroxaban and <120 days for dabigatran.

Conclusions

In a population-based study of patients receiving DOAC agents, we found apixaban had the most favorable GI safety profile and rivaroxaban the least favorable profile. GI bleeding events among patient aged 75 years or older taking DOACs increased with age; the risk was greatest among persons 75 years. Apixaban had the most favorable GI safety profile among all age groups.

Section snippets

Data Source

The data for this analysis came from OptumLabs Data Warehouse, which includes a geographically diverse adult population covered through both commercial insurance and Medicare Advantage in the United States.3 Inpatient, outpatient, and pharmacy claims data are available on >120 million enrollees. Medical claims include International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) diagnosis codes, ICD-9 procedure codes, Current Procedural Terminology, Version 4

Baseline Characteristics

There were 372,380 continuously enrolled patients who filled prescriptions for DOACs in the period of observation (October 1, 2010 to February 28, 2015) of which 182,896 had AF at baseline. After exclusion of patients with valvular heart disease, dialysis, kidney transplant, or end-stage renal disease (n = 180,328) we were left with a source population of 43,303 patients (6576 apixaban, 17,426 dabigatran, and 19,301 rivaroxaban), from which to create the propensity score matched sub-cohorts for

Discussion

This study directly compared the comparative risk of GI bleeding for each of the 3 DOACs (dabigatran, rivaroxaban, and apixaban) frequently used for the treatment of nonvalvular AF patients. Our use of a large administrative claims database of commercially insured US adult patients and enrollees in Medicare Advantage permitted the direct comparison between multiple DOACs using 1:1 propensity score matched sub-cohorts and Cox regression. We showed that there were significant differences in the

Acknowledgments

Author contributions: Study concept and design: Drs Abraham and Shah. Acquisition, analysis of data: Drs Shah, Abraham, Yao, and Ms Sangaralingham. Dr Yao had full access to the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Interpretation of data: Drs Abraham, Shah, Yao, Noseworthy, and Ms Sangaralingham.

Drafting of the manuscript: Drs Abraham, Shah, and Ms Sangaralingham. Critical revision of the manuscript for important

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    Conflicts of interest The authors disclose no conflicts.

    Funding This study was funded by the Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery. The design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication were solely the responsibility of the authors listed. Dr Yao had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis

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