Elevated Plasma Fibrinogen and Diabetes Mellitus Are Associated With Lower Inhibition of Platelet Reactivity With Clopidogrel
Lawrence Ang, BS,
Vachaspathi Palakodeti, MD, FACC,
Ahmer Khalid, BS,
Sotirios Tsimikas, MD, FACC,
Zaheib Idrees, BS,
Phillip Tran, MD,
Paul Clopton, MS,
Nayab Zafar, MD,
Guilherme Bromberg-Marin, MD,
Shahin Keramati, MD, FACC and
Ehtisham Mahmud, MD, FACC*
Division of Cardiovascular Medicine, University of California, San Diego School of Medicine, San Diego, California
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Figure 1 Patient Flow Diagram
Patients with established cardiovascular disease requiring treatment with clopidogrel were prospectively recruited from catheterization laboratories and outpatient clinics. The majority of subjects presented for evaluation of coronary artery disease (CAD). A subset of patients evaluated for CAD presented with symptoms of an acute coronary syndrome (ACS), including unstable angina or recent myocardial infarction (MI) >72 h before recruitment. PAD = peripheral arterial disease.
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Figure 2 Normal Distribution of Platelet Inhibition Achieved With Clopidogrel
The platelet response of 157 subjects with cardiovascular disease to clopidogrel therapy was measured with the rapid platelet function assay VerifyNow (Accumetrics, San Diego, California) and shows a normal, bell-shaped distribution (40.8 ± 26.2%).
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Figure 3 Platelet Inhibition With Clopidogrel as Stratified by Serum Fibrinogen Tertiles
Subjects with serum fibrinogen in the highest tertile range (>368 mg/dl) are observed to have significantly lower platelet inhibition with clopidogrel compared with subjects in the first and second tertiles with lower serum fibrinogen levels. Data are shown as mean ± standard error of mean. p = 0.032.
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Figure 4 Platelet Inhibition With Clopidogrel in Diabetic Patients With Elevated Fibrinogen
Subjects with both diabetes mellitus and elevated plasma fibrinogen ( 375 mg/dl) have significantly lower platelet inhibition with clopidogrel compared with nondiabetic patients or diabetic patients with lower fibrinogen levels. The adjusted platelet inhibition (mean ± SD) with the number of subjects in each group is shown.
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Figure 5 Platelet Inhibition With Clopidogrel as Stratified by BMI
Increased body mass index (BMI) (25 kg/m2) remains independently associated with lower platelet inhibition with clopidogrel regardless of diabetic status or fibrinogen level. The adjusted platelet inhibition (mean ± SD) in subjects with high and normal BMI is shown. p < 0.001.
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