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CLINICAL RESEARCH: ANTIPLATELET THERAPY

Elevated Plasma Fibrinogen and Diabetes Mellitus Are Associated With Lower Inhibition of Platelet Reactivity With Clopidogrel

Division of Cardiovascular Medicine, University of California, San Diego School of Medicine, San Diego, California

Manuscript received January 6, 2008; revised manuscript received May 27, 2008, accepted May 28, 2008.

^_* Reprint requests and correspondence: Dr. Ehtisham Mahmud, Cardiovascular Catheterization Laboratories, UCSD Medical Center, 200 West Arbor Drive, San Diego, California 92103 (Email: emahmud{at}ucsd.edu).

Objectives: The goal of this study was to identify factors associated with lower platelet inhibition (PI) with clopidogrel in subjects with cardiovascular disease (CVD).

Background: A heterogeneous platelet reactivity response to clopidogrel exists, and the clinical or biochemical predictors of suboptimal PI with clopidogrel remain unclear.

Methods: This study prospectively enrolled subjects with CVD requiring treatment with clopidogrel (75 mg daily for 7 days or 600-mg bolus 24 h before recruitment). A bedside rapid platelet function assay (VerifyNow, Acccumetrics, San Diego, California) to measure maximal and clopidogrel-mediated platelet reactivity was utilized, and factors associated with lower PI were identified.

Results: A heterogeneous, normally distributed PI (mean 40.8 ± 26.2%) response to clopidogrel was observed in 157 subjects (age 67.2 ± 12.2 years; 59.9% men). Multiple variable analysis of clinical and biochemical factors known to affect platelet reactivity revealed lower PI in patients with an elevated plasma fibrinogen level (375 mg/dl), diabetes mellitus, and increased body mass index (BMI) (25 kg/m²). On testing for interaction, elevated fibrinogen level was associated with diabetic status, resulting in lower PI in diabetic patients (23.9 ± 3.9% vs. 45.1 ± 4.5%, p < 0.001), but not nondiabetic patients (44.7 ± 4.4% vs. 46.3 ± 4.8%, p = 0.244). Increased BMI remained independently associated with lower PI after clopidogrel therapy regardless of diabetic status or fibrinogen level (36.8 ± 9.0% vs. 49.0 ± 7.0%, p < 0.001).

Conclusions: Elevated plasma fibrinogen (375 mg/dl) in the presence of diabetes mellitus and increased BMI (25 kg/m²) are associated with lower PI with clopidogrel in patients with CVD.

Key Words: fibrinogen • platelet aggregation • clopidogrel • diabetes mellitus • body mass index

Abbreviations and Acronyms   BMI = body mass index   CRP = C-reactive protein   CVD = cardiovascular disease   DM = diabetes mellitus   GP = glycoprotein   LTA = light transmittance aggregometry   PCI = percutaneous coronary intervention   PI = platelet inhibition   PRU = P2Y12 response units

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