A Model for Estimating the Risk of Gastrointestinal Bleeding for Patients on Oral Anticoagulants and Interacting Medications
Ainhoa Gomez‐Lumbreras, Abdelrahman G. Tawfik, Thomas Reese, Daniel M. Witt, Guilherme Del Fiol, Daniel C. MaloneABSTRACT
Introduction
Pharmacodynamic drug–drug interactions (DDI) in patients receiving oral anticoagulants (OAC) may increase the risk of gastrointestinal bleeding (GIB). The purpose of this study was to develop and validate a GIB model for patients receiving OACs.
Methods
A risk model, D rug I nteractions in O ral A nti C oagulants for Risk of G astro i ntestinal B leeding (DIOAC‐GIB), was developed to predict GIB based on interacting medications and other patient‐specific risk factors for patients on OAC. Inputs for the model were obtained using random‐effect meta‐analysis or from the literature for the following attributes: exposure to nonsteroidal anti‐inflammatory drugs (NSAIDs); selective serotonin reuptake inhibitors/serotonin‐norepinephrine reuptake inhibitors (SSRI/SNRIs); aspirin, antiplatelet medications, and proton pump inhibitors (PPIs); age; and GIB history. The model was correlated to existing OAC models (HAS‐BLED and DOAC score).
Results
GIB risk for OACs was based on pivotal trials (1.16% for apixaban; 3.15% for rivaroxaban; 3.00% for dabigatran; 3.31% for edoxaban; and 2.00% for warfarin). The odds ratio (OR) of GIB for NSAIDs ranged from 1.16 (95% confidence interval [CI]: 0.84–1.61) for celecoxib to 20.67 (95% CI: 14.56–29.34) for ketorolac. ORs for GIB among SSRI/SNRIs ranged from 1.31 (95% CI: 1.07–1.62) for paroxetine to 1.50 (95% CI: 1.32–1.70) for venlafaxine. Risk of GIB also included persons > 65 years of age (relative risk = 2.50, 95% CI: 1.2–5.5); history of GIB (OR = 5.14, 95% CI: 3.92–6.73); exposure to aspirin (OR = 1.31, 95% CI: 0.93–1.85), antiplatelet medications (OR = 1.97, 95% CI: 1.73–2.25), and corticosteroids (OR = 1.69, 95% CI: 1.53–1.87); and PPIs reduced GIB risk (OR = 0.67, 95% CI: 0.62–0.74). Correlations between the DIOAC‐GIB and HAS‐BLED and DOAC scores were 0.5 for both ( p < 0.01).
Conclusion
DIOAC‐GIB is a novel GIB‐risk model that incorporates pharmacodynamic OAC DDIs to assist clinicians and patients to determine a therapeutic plan while accounting for GIB risk. DIOAC‐GIB correlates with other bleeding risk scores and may help identify high‐risk patients who may benefit from tailored prescribing.