PCV75 Multi-center study on the impact of cytochrome P450 3A4 and P-glycoprotein interacting medications on bleeding and thromboembolism risk in nonvalvular atrial fibrillation patients managed on rivaroxaban therapy

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Conference Proceeding

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Value in Health


Objectives: Rivaroxaban is a known substrate of the cytochrome P450 3A4 (CYP3A4) enzyme and the P-glycoprotein (P-gp) efflux transport system. Theoretically, concomitant use of rivaroxaban with medications that inhibit CYP3A4 or P-gp would result in higher concentrations of rivaroxaban, thereby lowering thromboembolism risk and increasing bleeding risk. The purpose of this study is to evaluate the risk of bleeding and thromboembolism in patients with nonvalvular atrial fibrillation (NVAF) receiving rivaroxaban and concomitant medications known to affect the CYP3A4 and P-gp pathways using data from a consortium of non-profit healthcare systems. Methods: Medical and prescription claims from three large nonprofit integrated healthcare systems from the Health Care Systems Research Network (HCSRN) were extracted to analyze the association of bleed or thromboembolism risk during concomitant interacting medication (CIM) exposure within 12 months of prescription of rivaroxaban. Patients ≥18 years of age with NVAF, ≥1 prescription claim for rivaroxaban during January 1, 2012 through December 31, 2016, and continuous health plan enrollment ≥1 year prior to and after the first prescription claim date for rivaroxaban were included in the study. Patients were divided into CIM users and non-CIM users based on CIM exposure. Time to bleed or thromboembolism was described using Kaplan-Meier analysis. Multivariable logistic regression using a modified Poisson distribution assessed the association for outcomes, adjusting for clinical and demographic covariates. Results: After outcome-specific exclusions 1,371 were analyzed for bleed outcomes and 1,350 for thromboembolism. CIM use was significantly associated with reduced risk of thromboembolism in the adjusted model (RR=0.69; 95% CI:0.55-0.86) while CIM use showed no significant association with risk of bleed (RR=0.84; 95% CI:0.66-1.07). Conclusions: Concurrent use of rivaroxaban with CYP3A4 and P-gp inhibitors was associated with lower risk of thromboembolism in NVAF patients, but did not appear to increase bleeding risk, suggesting no clinically significant interactions of rivaroxaban with CYP3A4 or P-gp inhibitors.



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