The influence of ABCB1 rs4148738 (C>T) polymorphism on rivaroxaban exposure and bleeding risk in Iraqi patients with non-valvular atrial fibrillation

Background: Atrial fibrillation (AF) is a common arrhythmia linked to thromboembolic risks. Rivaroxaban, a direct oral anticoagulant, prevents strokes in non-valvular AF (NVAF) patients. However, the role of genetics in its pharmacokinetics and outcomes remains unclear.

Aim of study: To explore the link between the ABCB1 (rs4148738 C>T) polymorphism, rivaroxaban steady-state plasma levels, and the occurrence of bleeding events in AF patients.

Patients and methods: This cross-sectional study examines patients with AF treated with rivaroxaban anticoagulation from September 2024 to March 2025. We gathered clinical data covering demographics, comorbidities, and treatment adherence. Biochemical tests assessed renal function (serum creatinine and urea), and the steady-state plasma concentrations of rivaroxaban were determined via high-performance liquid chromatography. Genotyping was conducted using allele-specific polymerase chain reaction.

Results: The study enrolled 100 participants (45 males, 55 females), most aged >46 years, with an obesity prevalence of 52%. The genotype distribution was noted as 26% CC, 39% CT, and 35% TT. Plasma levels of rivaroxaban were significantly lower in homozygous mutants (TT) compared to wild-type genotypes (P = 0.001). The rs4148738 polymorphism was associated with bleeding events, all of which occurred in CT carriers. This observation should be considered preliminary due to the limited sample size.

Conclusion: The ABCB1 rs4148738 polymorphism influences rivaroxaban plasma levels in NVAF patients and shows a potential link to bleeding risk.