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An Exploratory Association Analysis of ABCB 1 rs1045642 and ABCB 1 rs4148738 with Non-Major Bleeding Risk in Atrial Fibrillation Patients Treated with Dabigatran or Apixaban

  • Roşian, Adela-Nicoleta1, 2
  • Iancu, Mihaela
  • Trifa, Adrian Pavel
  • Roşian, Ştefan Horia2, 3
  • Mada, Cristina2
  • Gocan, Cornelia Paula2
  • Niţă, Teodora2
  • Istratoaie, Sabina1
  • Boarescu, Paul-Mihai
  • Buzoianu, Anca Dana1
  • 1 (A.D.B.)
  • 2 (T.N.)
  • 3 Department of Cardiology—Heart Institute, “Iuliu Haţieganu” University of Medicine and Pharmacy Cluj-Napoca, 19-21 Calea Moților Street, 400001 Cluj-Napoca, Romania
Published Article
Journal of Personalized Medicine
Publication Date
Sep 18, 2020
DOI: 10.3390/jpm10030133
PMID: 32961964
PMCID: PMC7565454
PubMed Central


(1) Background: The approach of bleeding complications in patients treated with non-vitamin K oral anticoagulants (NOACs) represents an important issue in clinical practice. Both dabigatran and apixaban are substrates for P-glycoprotein and, therefore, ABCB 1 gene variations may be useful in individualizing NOACs treatment, especially in high-risk patients. (2) Methods: ABCB 1 rs1045642 and rs4148738 were determined in 218 atrial fibrillation patients treated with dabigatran or apixaban (70.94 ± 9.04 years; 51.83% men). (3) Results: Non-major bleeding appeared in 7.34% NOACs–treated patients. The logistic tested models based on the four genetic models revealed no significant association between the variant genotype of two ABCB 1 SNPs and the risk of bleeding ( p > 0.05). Among the four two-locus haplotypes, TA and CA haplotypes had the highest frequency in NOACs-treated patients with bleeding, involving a possible positive association with the susceptibility of bleeding complications (OR = 1.04 and OR = 1.91, respectively). The logistic model found no significant association of estimated haplotypes with bleeding ( p > 0.05) except for the TG haplotype which had a trend toward statistical significance ( p = 0.092). Among the risk factors for bleeding, only age > 70 years and stroke/TIA showed a tendency toward statistical significance. (4) Conclusions: We found no significant associations between the studied ABCB 1 variant genotypes with non-major bleeding risk in NOACs-treated patients. A trend of association between TG haplotype with bleeding risk was observed, implying a protective role of this haplotype against bleeding in patients treated with dabigatran or apixaban.

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