Korean Circ J.  2017 May;47(3):366-376. 10.4070/kcj.2016.0384.

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

• Park Y
• Kim KH
• Kang MG
• Ahn JH
• Jang JY
• Park HW
• Koh JS
• Park JR
• Hwang SJ
• Jeong YH
• Hwang JY
• Lee HR
• Kwak CH

• KMID: 2385391
• DOI: http://doi.org/10.4070/kcj.2016.0384

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.

Keyword

Atrial fibrillation; Platelet aggregation inhibitors; Blood platelets; Biomarker

MeSH Terms

Adenosine Diphosphate
Arachidonic Acid
Aspirin
Atrial Fibrillation*
Biomarkers
Blood Platelets
C-Reactive Protein
Collagen
Fibrinogen
Follow-Up Studies
Humans
Platelet Aggregation Inhibitors
Stroke
Adenosine Diphosphate
Arachidonic Acid
Aspirin
Biomarkers
C-Reactive Protein
Collagen
Fibrinogen
Platelet Aggregation Inhibitors

Figure

• 

  Fig. 1 Study flow diagram. AF: atrial fibrillation, CLPD: clopidogrel, CILO: cilostazol, PUFA: polyunsaturated fatty acid.

• 

  Fig. 2 Differences in platelet reactivity (A) and thrombogenic biomarkers (B) during aspirin monotherapy, according to the CHA2DS2-VASc scores. Red and grey bars represent the values in patients with low and high CHA2D2-VASc scores, respectively. The error bars denote the standard deviation. ADP: adenosine diphosphate, TRAP: thrombin receptor agonist peptide, Coll: collagen, AA: arachidonic acid, vWF:Ag: von Willebrand factor antigen, Fib: fibrinogen, hs-CRP: high sensitivity-C reactive protein.

• 

  Fig. 3 Thrombogenic biomarker levels during aspirin monotherapy and combination antiplatelet therapy. vWF:Ag: von Willebrand factor antigen, hs-CRP: high sensitivity-C reactive protein.

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  Fig. 4 Changes in ADP-mediated platelet reactivity and thrombogenic biomarkers. vWF:Ag: von Willebrand factor antigen, ADP: adenosine diphosphate.

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