Elevated plasma fibrinogen rather than residual platelet reactivity after clopidogrel pre-treatment is associated with an increased ischemic risk during elective percutaneous coronary intervention
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Published on: March 15, 2022
Lawrence Ang1, Khalid Bin Thani, Manjusha Ilapakurti
1Division of Cardiovascular Medicine, University of California-San Diego Sulpizio Cardiovascular Center, La Jolla, California 92037, USA.
Insights
Elevated serum fibrinogen, not platelet reactivity, independently predicts ischemic myocardial injury after percutaneous coronary intervention (PCI) with clopidogrel pre-treatment. This finding is crucial for managing PCI patients.
Area of Science:
- Cardiology
- Interventional Cardiology
- Biochemistry
Background:
- Elevated serum fibrinogen and high platelet reactivity are linked to ischemic cardiovascular events.
- High fibrinogen levels may contribute to reduced effectiveness of antiplatelet drugs like clopidogrel.
- The independent or interactive roles of fibrinogen and platelet reactivity in post-PCI ischemic events remain unclear.
Purpose of the Study:
- To investigate the independent and interactive roles of serum fibrinogen and residual platelet reactivity in ischemic events following elective percutaneous coronary intervention (PCI).
- To determine if elevated fibrinogen or high on-clopidogrel platelet reactivity are independent predictors of periprocedural myocardial infarction (PPMI).
Main Methods:
- Prospective enrollment of 189 patients undergoing elective PCI with clopidogrel pre-treatment.
- Measurement of baseline serum fibrinogen and platelet function using the VerifyNow P2Y12 assay.
- Monitoring for ischemic myocardial injury markers (troponin I/T, CK-MB) post-PCI.
Main Results:
- Elevated fibrinogen was independently associated with both troponin-defined (13.9%) and CK-MB-defined (5.8%) PPMI.
- Higher fibrinogen levels and older age were linked to increased PPMI risk.
- Residual platelet reactivity, measured by VerifyNow P2Y12, was not associated with PPMI.
Conclusions:
- Elevated serum fibrinogen is an independent predictor of ischemic myocardial injury after elective PCI, irrespective of platelet reactivity.
- Fibrinogen levels ≥345 mg/dl significantly correlated with PPMI, particularly in the absence of systemic inflammation.
- These findings highlight fibrinogen as a key risk factor in patients undergoing PCI.
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.
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