Drug-Drug Interactions with Oral Anticoagulants as Potentially Inappropriate Medications: Prevalence and Outcomes in Elderly Patients in Primary Care and Hospital Settings

Direct oral anticoagulants and vitamin K antagonists are considered as potentially inappropriate medications (PIM) in several situations according to Beers Criteria. Drug-drug interactions (DDI) occurring specifically with these oral anticoagulants considered PIM (PIM-DDI) is an issue since it could enhance their inappropriate character and lead to adverse drug events, such as bleeding events. The aim of this study was (1) to describe the prevalence of oral anticoagulants as PIM, DDI and PIM-DDI in elderly patients in primary care and during hospitalization and (2) to evaluate their potential impact on the clinical outcomes by predicting hospitalization for bleeding events using machine learning methods. This retrospective study based on the linkage between a primary care database and a hospital data warehouse allowed us to display the oral anticoagulant treatment pathway. The prevalence of PIM was similar between primary care and hospital setting (22.9% and 20.9%), whereas the prevalence of DDI and PIM-DDI were slightly higher during hospitalization (47.2% vs. 58.9% and 19.5% vs. 23.5%). Concerning mechanisms, combined with CYP3A4-P-gp interactions as PIM-DDI, were among the most prevalent in patients with bleeding events. Although PIM, DDI and PIM-DDI did not appeared as major predictors of bleeding events, they should be considered since they are the only factors that can be optimized by pharmacist and clinicians.