Potentially Clinically Relevant Drug-Drug Interactions with Direct Oral Anticoagulants: Prevalence and Contributing...

Direct oral anticoagulants (DOACs) are widely prescribed but remain susceptible to drug-drug interactions (DDIs) that increase bleeding or thrombotic risk. The real-world prevalence and factors associated with potentially clinically relevant DDIs in patients on chronic DOAC therapy require further study.

To determine the prevalence of clinically relevant DDIs involving DOACs and identify patient- and treatment-related factors associated with their occurrence.

A retrospective cross-sectional study was conducted among hospitalized adults receiving a DOAC as a home medication. Potentially clinically relevant DDIs were identified from documented home medications using the Lexicomp Online 2025 Drug Interactions database and classified as category C (monitor therapy), D (consider modification), and X (avoid combination). Clinical bleeding, thromboembolic, or other adverse outcomes were not assessed. Descriptive statistics and multivariable logistic regression analyzed patient characteristics and factors associated with DDIs.

Among 870 patients (mean age 71.4 ± 13.0 years), 72.8% had at least one potentially clinically relevant DDI. Among patients with at least one potentially clinically relevant DDI, 47.4% had multiple interactions. Most were Category C (97.6%), primarily involving antidepressants with antiplatelet activity (30.4%), antiplatelet agents (30.0%), amiodarone (8.5%), and NSAIDs (7.9%). Category D and X interactions (2.4%) mainly involved CYP3A4/P-gp inhibitors or inducers such as dronedarone, erythromycin, and phenytoin. Independent predictors of DDI occurrence included the number of medications (OR 1.14; 95% CI 1.09-1.19; p < 0.0001), coronary artery disease (OR 1.55; p = 0.039), anxiety (OR 2.02; p = 0.016), dementia (OR 2.99; p = 0.006), and depression (OR 3.27; p = 0.001).

Potentially clinically relevant DDIs involving DOACs were common in this hospitalized cohort, although most identified interactions were Category C and therefore primarily warranted monitoring. Higher medication burden and several comorbidities, including coronary artery disease, depression, anxiety and dementia were associated with the presence of potentially clinically relevant DDIs. Vigilant medication review is essential to enhance safety.