Elevated plasma fibrinogen rather than residual platelet reactivity after clopidogrel pre-treatment is associated with an increased ischemic risk during elective percutaneous coronary intervention

J Am Coll Cardiol. 2013 Jan 8;61(1):23-34. doi: 10.1016/j.jacc.2012.09.037.


Objectives: This study was undertaken to determine the roles of serum fibrinogen and residual platelet reactivity after clopidogrel pre-treatment on ischemic events after elective percutaneous coronary intervention (PCI).

Background: Both elevated serum fibrinogen and high platelet reactivity with thienopyridines are associated with ischemic cardiovascular events. Elevated fibrinogen also contributes to high on-clopidogrel platelet reactivity. It is unknown whether fibrinogen and residual platelet reactivity are associated with adverse cardiovascular events through independent or interactive effects.

Methods: A total of 189 patients undergoing elective PCI with clopidogrel pre-treatment (75 mg daily for ≥7 days or a 600-mg bolus ≥12 h before recruitment) were prospectively enrolled. Baseline fibrinogen and platelet function using the VerifyNow P2Y12 assay (Accumetrics, San Diego, California) were obtained. Markers of ischemic myocardial injury were measured every 8 h after PCI.

Results: Incidence of troponin-defined periprocedural myocardial infarction (PPMI) (troponin I/T >3× upper limit of normal) was 13.9% and associated with elevated fibrinogen (363.1 ± 131.0 mg/dl vs. 309.1 ± 99.6 mg/dl; p = 0.017), higher age (68.2 ± 10.1 years vs. 63.0 ± 11.8 years; p = 0.040), and elevated platelet count. Fibrinogen level and age remained independently associated with PPMI following multiple variable and interaction testing. The incidence of creatine kinase-myocardial band (CK-MB)-defined PPMI (CK-MB >3× upper limit of normal) was 5.8% and associated with elevated fibrinogen (403.4 ± 128.0 mg/dl vs. 313.5 ± 104.6 mg/dl; p = 0.007). Platelet reactivity measurements were not associated with PPMI by either definition. Fibrinogen ≥345 mg/dl was significantly associated with both CK-MB-defined (p = 0.026) and troponin I/T-defined PPMI (p = 0.036). Fibrinogen effects were most prominent in the absence of systemic inflammation (C-reactive protein ≤0.5 mg/dl).

Conclusions: Elevated fibrinogen is independently associated with the risk of ischemic myocardial injury following elective PCI with clopidogrel pre-treatment regardless of platelet reactivity as measured by the VerifyNow assay.

MeSH terms

  • Aged
  • Blood Platelets / drug effects*
  • C-Reactive Protein / analysis
  • Clopidogrel
  • Coronary Artery Disease / therapy
  • Creatine Kinase, MB Form / blood
  • Female
  • Fibrinogen / analysis*
  • Humans
  • Male
  • Middle Aged
  • Myocardial Infarction / blood
  • Myocardial Infarction / etiology*
  • Percutaneous Coronary Intervention*
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Platelet Count
  • Platelet Function Tests
  • Predictive Value of Tests
  • Premedication
  • Prospective Studies
  • ROC Curve
  • Sensitivity and Specificity
  • Ticlopidine / analogs & derivatives*
  • Ticlopidine / therapeutic use
  • Troponin / blood


  • Platelet Aggregation Inhibitors
  • Troponin
  • Fibrinogen
  • C-Reactive Protein
  • Clopidogrel
  • Creatine Kinase, MB Form
  • Ticlopidine