Elevated Plasma Fibrinogen Rather Than Residual Platelet Reactivity After Clopidogrel Pre-Treatment Is Associated With an Increased Ischemic Risk During Elective Percutaneous Coronary Intervention

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 >3x 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 >3x 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. (J Am Coll Cardiol 2013;61:23-34) (C) 2013 by the American College of Cardiology Foundation