Author + information
- Received May 14, 2012
- Revision received September 11, 2012
- Accepted September 25, 2012
- Published online January 8, 2013.
- Lawrence Ang, MD⁎,
- Khalid Bin Thani, MD, MAS⁎,
- Manjusha Ilapakurti, MBBS, MPH⁎,
- Michael S. Lee, MD†,
- Vachaspathi Palakodeti, MD⁎ and
- Ehtisham Mahmud, MD⁎,⁎ ()
- ↵⁎Reprint requests and correspondence:
Dr. Ehtisham Mahmud, Sulpizio Cardiovascular Center, University of California, San Diego, 9434 Medical Center Drive, La Jolla, California 92037
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.
Dr. Lee is a consultant for Abbott Vascular, Boston Scientific, St. Jude Medical, Medtronic, and Sanofi-Aventis. Dr. Mahmud has received clinical trial support from Accumetrics, Eli Lilly, and Sanofi-Aventis; and is on the Speakers Bureau for Medtronic. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Drs. Ang and Bin Thani are joint first authors.
- Received May 14, 2012.
- Revision received September 11, 2012.
- Accepted September 25, 2012.
- American College of Cardiology Foundation