The Influence of ABCB1 (rs1045642 and rs4148738) Gene Polymorphisms on Rivaroxaban Pharmacokinetics in Patients Aged 80 Years and Older with Nonvalvular Atrial Fibrillation.

Abstract

ABCB1 gene polymorphisms are associated with rivaroxaban distribution changes and adverse reactions but the data are controversial. Toevaluate the influence of ABCB1 (rs1045642 and rs4148738) gene polymorphisms on rivaroxaban pharmacokinetics in patients aged 80 years and older with nonvalvular atrial fibrillation (NAF). 128 patients aged 80 years and older (median [Me] age 87.5 [83.0-90.0] years) with NAF were included. We performed ABCB1 (rs1045642 and rs4148738) genotyping, measured the trough steady-state plasma concentration (Cmin,ss) of rivaroxaban and prothrombin time (PT) and analyzed prior medical records for clinically relevant non-major bleeding (CRNMB). CC genotype carriers had no differences in Cmin,ss (p>0.05) compared with the CT and TT rs1045642 and rs4148738 genotypes carriers. CC genotype carriers had no differences in PT (p>0.05) compared with the CT rs1045642 and rs4148738 and TT rs4148738 genotypes carriers. In the TT genotype PT levels were higher than in the CC rs1045642 genotype: Me 14.2 [13.0-16.1] sec vs 13.3 [12.4-14.5] sec (p=0.049). Incidence of CRNMB was higher in patients with the TT genotype compared with the CC rs1045642 (29.3% vs 4.5%, p=0.021) and rs4148738 (39.3% vs 8.1%, p=0.008) and the CT genotype rs4148738 (39.3% vs 14.3%, p=0.002). ABCB1 (rs1045642 and rs4148738) polymorphisms didn't influence rivaroxaban pharmacokinetics in patients aged 80 years and older with NAF. TT carriers developed CRNMB more frequently compared with the CC rs1045642 and the CC and CT rs4148738 genotypes. The haplotype TT-TT haplotype was associated with a higher frequency of CRNMB.