Conclusion
This study demonstrated an increased risk of bleeding in Asian patients taking simvastatin concomitantly with rivaroxaban, suggesting potential clinically relevant pharmacokinetic and pharmacodynamic interactions between the two drugs. Current European guideline suggests no notable anticipated effects of atorvastatin on the area-under-the-curve of rivaroxaban, and does not recommend a need for dose adjustment of the DOAC [8], while simvastatin was not mentioned. We suggest that the drug-drug interactions between rivaroxaban and simvastatin should be further investigated using physiologically-based pharmacokinetic modeling. The mechanistic explanation of the interaction could hold important clues towards concomitant use of drugs of similar disposition profile, particularly when DOAC effects or plasma concentrations are not routinely measured nor readily accessible.