(C-232) Thrombosis and Bleeding Risk in Patients Receiving NOACs and P-gp Inducers or Inhibitors: A Case-Case-Time-Control for Drug Interactions Assessment

Background: P-glycoprotein (P-gp) is a drug efflux transporter that can influence drug bioavailability. Concomitant use of drugs that induce or inhibit P-gp may affect the plasma levels of non-vitamin K antagonist oral anticoagulants (NOACs) and likely alter their effectiveness and safety profile.

Objectives: To evaluate the potential drug interaction on the thrombosis and bleeding risk in patients exposed to NOACs and drugs that induce or inhibit P-gp.

Methods: We employed a case-time-control (CCTC) analysis, which consisted of a case-crossover and a control crossover analysis matching on sex, age, and the case time, to address the potential secular trend of exposure. We retrieved data from the Taiwan National Health Insurance Research Database and identified patients with atrial fibrillation who were hospitalized due to thrombosis or major bleeding events between 2011 and 2021. We defined the first event as the index date (day 0). We defined a 30-day hazard period (from day -1 to day -30) and a 30-day reference period randomly selected based on one of four washout intervals: 30, 60, 90, or 120 days before the hazard period. Conditional logistic regression was performed to estimate the odds ratio (OR) of thrombosis and bleeding risk associated with NOACs that combined with P-gp inducer, inhibitors or neither, respectively.

Results: We found that patients used NOACs and P-gp inhibitors were associated with an increased risk of bleeding (OR 1.49, 95% CI 1.29–1.72). Although those exposed to NOACs and P-gp inducers were not associated with the increased risk of bleeding (0.94; 0.43–2.04), it raised the risk of thrombosis (2.90; 0.96-8.75).

Conclusions: Our results indicated that patients using NOACs and drug that induce or inhibit P-gp were associated varied risk profiles of thrombosis and bleeding. These findings may suggest a potential drug interaction for those with NOACs and drugs that influence P-gp.