BackgroundThe influence of genetic factors on the pharmacokinetics and clinical outcomes of rivaroxaban in patients with non-valvular atrial fibrillation (NVAF) is poorly understood. This study aimed to explore the effects ofCYP3A4/5,ABCB1, andABCG2gene polymorphisms on the trough concentrations and the bleeding risk of rivaroxaban in NVAF patients.Patients and methodsThis study is a prospective multicenter study. The patient's blood samples were collected to detect the steady-state trough concentrations of rivaroxaban and gene polymorphisms. We visited the patients regularly at month 1, 3, 6, and 12 to record bleeding events and medications.ResultsA total of 95 patients were enrolled in this study, and 9 gene loci were detected. For the dose-adjusted trough concentration ratio (Ctrough/D) of rivaroxaban, the homozygous mutant type was significantly lower than wild type atABCB1rs4148738 locus (TT vs. CC,P= 0.033), and the mutant type was significantly lower than the wild type atABCB1rs4728709 locus (AA + GA vs. GG,P= 0.008).ABCB1(rs1045642, rs1128503),CYP3A4(rs2242480, rs4646437),CYP3A5(rs776746), andABCG2(rs2231137, rs2231142) gene polymorphisms had no significant effect on the Ctrough/D of rivaroxaban. For the bleeding events, we found that there were no significant differences among genotypes of all gene loci.ConclusionThis study found for the first time thatABCB1rs4148738 and rs4728709 gene polymorphisms had a significant impact on the Ctrough/D of rivaroxaban in NVAF patients.CYP3A4/5,ABCB1, andABCG2gene polymorphisms were not associated with the bleeding risk of rivaroxaban.