title: Elevated plasma fibrinogen rather than residual platelet reactivity after clopidogrel pre-treatment is associated with an increased ischemic risk during elective percutaneous coronary intervention.
abstract: OBJECTIVE
  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.
authors.affiliation: Division of Cardiovascular Medicine, University of California-San Diego Sulpizio Cardiovascular Center, La Jolla, California 92037, USA.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Ang
authors.forename: Khalid Bin
authors.initials: KB
authors.lastname: Thani
authors.forename: Manjusha
authors.initials: M
authors.lastname: Ilapakurti
authors.forename: Michael S
authors.initials: MS
authors.lastname: Lee
authors.forename: Vachaspathi
authors.initials: V
authors.lastname: Palakodeti
authors.forename: Ehtisham
authors.initials: E
authors.lastname: Mahmud
mesh_terms: D000368:Aged; D001792:Blood Platelets / Q000187:drug effects*; D002097:C-Reactive Protein / Q000032:analysis; D000077144:Clopidogrel; D003324:Coronary Artery Disease / Q000628:therapy; D052279:Creatine Kinase, MB Form / Q000097:blood; D005260:Female; D005340:Fibrinogen / Q000032:analysis*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000209:etiology*; D062645:Percutaneous Coronary Intervention; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D010976:Platelet Count; D010979:Platelet Function Tests; D011237:Predictive Value of Tests; D011292:Premedication; D011446:Prospective Studies; D012372:ROC Curve; D012680:Sensitivity and Specificity; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D014336:Troponin / Q000097:blood
chemical_list: D010975:Platelet Aggregation Inhibitors; D014336:Troponin; D005340:Fibrinogen; D002097:C-Reactive Protein; D000077144:Clopidogrel; D052279:Creatine Kinase, MB Form; D013988:Ticlopidine