The Impact of CYP3A4/5 Polymorphism on Anti-Factor Xa Activity in Iranian Patients with Atrial Fibrillation Receiving Rivaroxaban
نویسندگان
1 Tehran Heart Center, Cardiovascular Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
2 Tehran Heart Center, Cardiovascular Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
3 Tehran Heart Center, Cardiovascular Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
4 Tehran Heart Center, Cardiovascular Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
5 Department of Clinical Pharmacy and Pharmacoeconomics, School of Pharmacy, Iran University of Medical Sciences, Tehran, Iran
6 Department of Clinical Pharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
7 Tehran Heart Center, Cardiovascular Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
8 Tehran Heart Center, Cardiovascular Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
doi
10.22034/ircmj.2025.501538.1819چکیده
Background and Objectives: Direct oral anticoagulants including rivaroxaban are now the standard treatment for anticoagulation in patients with atrial fibrillation (AF). Rivaroxaban is primarily metabolized by P-glycoprotein and cytochrome P450 (CYP450) pathways and its efficacy can be affected by mutations in genes encoding these proteins/transporters. The present study evaluates whether CYP3A4/5 polymorphisms have an association with anti-factor-Xa activity in Iranian patients with AF undertaking rivaroxaban. Methods: This is a prospective observational single center study in which patients with AF receiving standard doses of rivaroxaban are included. Genotyping of polymorphisms CYP3A4*1B (rs2740574), CYP3A4*22 (rs35599367) and CYP3A5*3 (rs776746) is assessed and the association of these polymorphisms with anti-factor-Xa activity is determined. Association of anti-factor-Xa activity with polymorphisms is determined via linear regression analysis measured by SPSS software. Results: The study includes 92 patients of which 25 patients (27.2%) had at least one allele (two of them were mutant and the rest were heterozygote). Sixteen patients had heterozygote CYP3A5*3, 9 patients had CYP3A4*1B, and 1 patient had CYP3A4*22. Our data shows CYP3A4/5 polymorphism has a negative association with anti-factor-Xa activity both before (B1: -1.20, [95% CI: -0.68 to -1.72], P < 0.001) and after (B1: -1.15, [95% CI: -0.60 to -1.70], P < 0.001) adjustment for age and estimated glomerular filtration rate. Conclusion: There is a negative association between CYP3A4/5 polymorphism and anti-factor-Xa activity in patients with AF receiving rivaroxaban and CYP3A4/5 polymorphism results in lower anti-factor-Xa activity in this population. The possible effects of this association on clinical outcomes have yet to be determined.
