Key result
Verapamil combined with rivaroxaban is linked to ~75% non-major bleeding rates in ABCB1 TT carriers.
Why the study?
P-glycoprotein inhibitors and certain ABCB1 polymorphisms can increase rivaroxaban concentrations and bleeding risk, but their interaction in very elderly patients with non-valvular atrial fibrillation required evaluation.
Does the ABCB1 genotype affect the drug-drug interaction and bleeding risk of rivaroxaban combined with verapamil or amlodipine in patients over 80 with non-valvular atrial fibrillation?
Cross-Sectional (n=128)
No
Does the ABCB1 genotype affect the drug-drug interaction and bleeding risk of rivaroxaban combined with verapamil or amlodipine in patients over 80 with non-valvular atrial fibrillation?
p-value: p=<0.017
In patients aged 80 and older taking rivaroxaban, co-administration with verapamil significantly increases bleeding risk in ABCB1 TT carriers, suggesting the utility of genetic testing before adding P-gp inhibitors.
May increase CRNM bleeding risk with verapamil-rivaroxaban in ABCB1 TT carriers ≥80; leaves open utility of genotyping in prospective AF studies.
Background . The use of P-glycoprotein (P-gp) inhibitors and carriage of certain ABCB1 polymorphisms can lead to increased concentrations of rivaroxaban and the development of bleeding. The aim of the study . To study the features of drug-drug interactions (DDI) of rivaroxaban in patients over 80 years of age with non-valvular atrial fibrillation depending on the ABCB1 genotype (rs1045642 and rs4148738) using the example of verapamil (P-gp inhibitor) and amlodipine. Materials and methods . One hundred and twenty-eight patients were examined (median age – 87.5 [83–90] years). Genotyping, determination of the minimum equilibrium concentration of rivaroxaban (C min, ss ), with standardization for the daily dose (C min, ss /D), coagulogram and analysis of medical documentation for the presence of clinically relevant non-major bleeding (CRNM) were carried out. Analysis of CRNM was performed depending on the ABCB1 genotype. Results . The use of rivaroxaban with verapamil in comparison with patients not taking calcium channel blockers (CCBs) leads to high C min, ss values in the CC genotype (rs1045642, rs4148738); С min, ss and С min, ss /D in the CT genotype (rs1045642); prothrombin time in the CC genotype (rs1045642), more frequent occurrence of CRNM in the TT genotype (rs1045642, rs4148738). In comparison with patients taking amlodipine, it leads to high C min, ss values in the CT genotype (rs1045642), a more frequent occurrence of CRNM in the TT genotype (rs1045642, rs4148738). The use of rivaroxaban with amlodipine in comparison with patients not taking CCBs leads to high C min, ss and C min, ss /D values in the CC genotype (rs1045642) (p < 0.017). Conclusion . The use of verapamil with rivaroxaban in ABCB1 TT carriers (rs4148738 and rs4148738) leads to the development of CRNM in 75 and 78 % of cases, respectively. In patients taking rivaroxaban, it is advisable to test the ABCB1 genotype (rs4148738 and rs4148738) before adding a P-gp inhibitor to therapy.
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Сычев et al. (2024) conducted a cross-sectional in non-valvular atrial fibrillation (n=128). Calcium channel blockers (verapamil or amlodipine) in ABCB1 genotype carriers vs. Rivaroxaban without calcium channel blockers was evaluated on Clinically relevant non-major bleeding (CRNM) and minimum equilibrium concentration of rivaroxaban (Cmin,ss) (p=<0.017). The use of verapamil with rivaroxaban in ABCB1 TT carriers led to the development of clinically relevant non-major bleeding in 75% and 78% of cases.
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