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Antiplatelet Therapy Combinations and Thrombogenicity in Patients with Non-Valvular Atrial Fibrillation

  • Park, Yongwhi (Department of Internal Medicine, Gyeongsang National University School of Medicine, Cardiovascular Center, Gyeongsang National University Changwon Hospital) ;
  • Kim, Kye Hwan (Department of Internal Medicine, Gyeongsang National University School of Medicine, Gyeongsang National University Hospital) ;
  • Kang, Min Gyu (Department of Internal Medicine, Gyeongsang National University School of Medicine, Gyeongsang National University Hospital) ;
  • Ahn, Jong-Hwa (Department of Internal Medicine, Gyeongsang National University School of Medicine, Cardiovascular Center, Gyeongsang National University Changwon Hospital) ;
  • Jang, Jeong Yoon (Department of Internal Medicine, Gyeongsang National University School of Medicine, Cardiovascular Center, Gyeongsang National University Changwon Hospital) ;
  • Park, Hyun Woong (Department of Internal Medicine, Gyeongsang National University School of Medicine, Gyeongsang National University Hospital) ;
  • Koh, Jin-Sin (Department of Internal Medicine, Gyeongsang National University School of Medicine, Gyeongsang National University Hospital) ;
  • Park, Jeong-Rang (Department of Internal Medicine, Gyeongsang National University School of Medicine, Gyeongsang National University Hospital) ;
  • Hwang, Seok-Jae (Department of Internal Medicine, Gyeongsang National University School of Medicine, Gyeongsang National University Hospital) ;
  • Jeong, Young-Hoon (Department of Internal Medicine, Gyeongsang National University School of Medicine, Cardiovascular Center, Gyeongsang National University Changwon Hospital) ;
  • Hwang, Jin-Yong (Department of Internal Medicine, Gyeongsang National University School of Medicine, Gyeongsang National University Hospital) ;
  • Lee, Hye Ryun (Department of Laboratory Medicine, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine) ;
  • Kwak, Choong Hwan (Department of Internal Medicine, Gyeongsang National University School of Medicine, Cardiovascular Center, Gyeongsang National University Changwon Hospital)
  • Received : 2016.10.31
  • Accepted : 2016.12.29
  • Published : 2017.05.31

Abstract

Background and objectives: Combination antiplatelet therapy reduces the risk of ischemic stroke compared with aspirin monotherapy in non-valvular atrial fibrillation (NVAF) patients. The underlying mechanism, however, remains unclear. In addition, the association between platelet inhibition and thrombogenicity in NVAF has not been evaluated. Subjects and methods: We randomized 60 patients with NVAF that were taking 100 mg of aspirin daily (>1 month) to adding 75 mg of clopidogrel daily (CLPD group), 100 mg of cilostazol twice daily (CILO group), or 1000 mg of omega-3 polyunsaturated fatty acid twice daily (PUFA group). Biomarkers (von Willebrand factor antigen [vWF:Ag], fibrinogen, D-dimer, and high-sensitivity C-reactive protein [hs-CRP]) and platelet reactivity (PR), which were the levels stimulated by adenosine diphosphate (ADP), thrombin-receptor agonist peptide, collagen, and arachidonic acid, were measured at baseline and 30-day follow-up. Results: Combination antiplatelet therapy significantly reduced vWF:Ag and fibrinogen levels (7.7 IU/dL, p=0.015 and 15.7 mg/dL, p=0.005, respectively), but no changes were found in D-dimer and hs-CRP levels. The CLPD and CILO groups showed fibrinogen and vWF:Ag level reductions (24.9 mg/dL, p=0.015 and 9.3 IU/dL, p=0.044, respectively), whereas the PUFA group did not show any differences in biomarkers. Irrespective of regimen, the changes in fibrinogen and vWF:Ag levels were mainly associated with the change in ADP-mediated PR (r=0.339, p=0.008 and r=0.322, p=0.012, respectively). Conclusion: In patients with NVAF, combination antiplatelet therapy showed reductions for vWF:Ag and fibrinogen levels, which may be associated with the inhibitory levels of ADP-mediated PR. The clinical implications of these findings need to be evaluated in future trials.

Keywords

Acknowledgement

Supported by : Gyeongsang National University

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