Gastroenterology

Gastroenterology

Volume 149, Issue 3, September 2015, Pages 586-595.e3
Gastroenterology

Original Research
Full Report: Clinical—Alimentary Tract
Prevention of Dabigatran-Related Gastrointestinal Bleeding With Gastroprotective Agents: A Population-Based Study

https://doi.org/10.1053/j.gastro.2015.05.002Get rights and content

Background & Aims

Use of dabigatran, an inhibitor of thrombin, increases the risk of gastrointestinal bleeding (GIB). However, it is not clear whether gastroprotective agents (GPAs) prevent GIB in dabigatran users. We investigated the risk of GIB and the role of gastroprotective agents (including proton pump inhibitors and histamine type-2–receptor antagonists) in patients using dabigatran.

Methods

We performed a retrospective cohort study using a population-wide database managed by the Hong Kong Hospital Authority. Patients newly prescribed dabigatran from 2010 through 2013 were included in the analysis. Poisson regression was used to assess the risk of GIB in dabigatran users by incidence rate ratio (IRR), adjusted for patient characteristics, comorbidities, and concurrent medications.

Results

Among the 5041 patients newly prescribed dabigatran, 124 (2.5%) developed GIB during follow-up evaluation (4.2/100 patient-years). The risk of GIB in this population increased among patients 75 years and older (IRR, 2.47; 95% confidence interval [CI], 1.66–3.68), patients with a history of peptic ulcers or GIB (IRR, 2.31; 95% CI, 1.54–3.46), and patients who used aspirin (IRR, 1.52; 95% CI, 1.03–2.24). Concomitant use of gastroprotective agents was associated with a reduced risk of GIB (IRR, 0.52; 95% CI, 0.35–0.77). Subcategory analysis showed that use of proton pump inhibitors (IRR, 0.53; 95% CI, 0.31–0.91) or histamine type-2–receptor antagonists (IRR, 0.61; 95% CI, 0.40–0.94) were associated with a lower risk of GIB. Further analysis showed that the risk reduction by gastroprotective agents was significant for only upper GIB (IRR, 0.29; 95% CI, 0.15–0.54), and only for patients with a prior history of peptic ulcers or GIB (IRR, 0.14; 95% CI, 0.06–0.30).

Conclusions

In the Hong Kong population, use of gastroprotective agents was associated with a reduced risk of GIB in patients taking dabigatran. The association was stronger for upper GIB than lower GIB, and in patients with a prior history of peptic ulcers or GIB.

Section snippets

Data Source

This study used the electronic medical records of the Clinical Data Analysis and Reporting System (CDARS) of the Hong Kong Hospital Authority (HA), which is the sole public-funded health care provider of Hong Kong. The HA currently serves a population of more than 7 million, managing 42 hospitals, 47 Specialist Out-patient Clinics, and 73 General Out-patient Clinics organized into 7 hospital clusters according to geographic location.11 The HA uses the Clinical Management System (CMS), a

Data Validation

Among the 5041 patients on dabigatran included in this study, 711 patients (14.1%) were from the HKW cluster (Supplementary Figure 1). Of these, we selected all patients who had a diagnosis of GIB (n = 35), all patients with prior history of peptic ulcer/GIB (n = 78), and a random sample of 133 patients (20%) who had AF. As negative controls, we selected a random sample of 66 patients (10%) who did not develop GIB, a random sample of 63 patients (10%) who did not have a prior history of peptic

Discussion

Gastrointestinal bleeding is a major adverse clinical outcome associated with use of the NOACs. In particular, bleeding risk appears to be higher for dabigatran when compared with other NOACs.6 Because there currently is no effective antidote for dabigatran, patients are potentially at a higher risk of uncontrolled GIB compared with warfarin, which can be reversed by vitamin K and fresh-frozen plasma. This would highlight the importance of identifying a preventive strategy for GIB in patients

Conclusions

This study showed that the risk factors of GIB in our patients prescribed dabigatran included ages 75 or older, history of peptic ulcer or GIB, and concomitant use of aspirin. Gastroprotective agents were associated with a reduced risk of GIB in patients on dabigatran. The protective effect seemed to be more for prevention of upper GIB and among those with a prior history of peptic ulcers or GIB. Hence, gastroprotective agents should be considered in high-risk patients taking dabigatran.

Acknowledgment

The authors thank our colleagues in the Department of Pharmacology and Pharmacy of the University of Hong Kong: Ms Celine S. L. Chui for her contribution to initial data retrieval; Mr Kenneth K. C. Man for cross-checking the statistical analysis; and Mrs Lisa Wong for proofreading the manuscript.

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    Conflicts of interest These authors disclose the following: Esther Chan has received research support from Bristol-Myers Squibb and Janssen (a division of Johnson and Johnson), and Wai K. Leung has received speaker fees from Eisai, Ferring, Menarini, and Takeda, and also serves on the advisory boards of AbbVie, Boehringer-Ingelheim, and Janssen. The remaining authors disclose no conflicts.

    Funding This study was supported by the General Research Fund, Research Grants Council, Hong Kong (project number: 17102314).

    Author names in bold designate shared co-first authors.

    Authors share co-first authorship.

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