News:Elevated Plasma Fibrinogen Levels among Diabetics and Increased BMI are Associated with Reduced Platelet Inhibition with Clopidogrel

September 16, 2008 By Vijayalakshmi Kunadian MBBS MD MRCP [mailto:vkunadian@perfuse.org]

Platelet inhibition (PI) varies between patients treated with antiplatelet therapy. Increased tendency for platelet aggregation are observed among patients with diabetes, smoking, hyperlipidemia, higher fibrinogen levels and among patients with history of coronary atherosclerosis. Several platelet function assays are available to study platelet aggregation response. The VerifyNow system (Accumetrics, San Diego, California) utilizes photospectometry to measure light transmittance in whole samples of blood.

Ang and colleagues from the University of California, San Diego School of Medicine, San Diego, California conducted a study to determine the level of platelet inhibition obtained with clopidogrel measured with the VerifyNow system among patients with cardiovascular disease and to identify the role of clinical and biochemical factors known to affect platelet aggregation response to clopidogrel.

Patients with established cardiovascular disease undergoing treatment with clopidogrel 75 mg daily for a minimum of 7 days or administered a 600mg bolus for at least 24 hours before study enrollment were included in the study. Patients with thrombocytopenia, inherited platelet disorders, glycoprotein IIbIIIa inhibitor administration, elevated serum triglyceride levels and those with chronic liver disease were excluded from the study.

This study consisted of 157 patients who had treatment with clopidogrel. The mean age was 67.2±12.2 years. In total 137 patients had clopidogrel for ≥7 days and the rest received a 600mg bolus dose. Around 89.1% of patients received concomitant aspirin therapy. The mean platelet inhibition was 40.8±26.2%. The presence of elevated fibrinogen levels, venous blood sampling, nitrate therapy, history of hyperlipidemia and elevated serum triglyceride level demonstrated a significant relation with platelet inhibition achieved. Significantly lower platelet inhibition was achieved at the highest tertile of fibrinogen level compared with the first and second tertiles (32.8±23.7%, p=0.032). Aspirin co-administration, indicators of inflammation, prior cardiovascular history and smoking did not demonstrate a significant relation with PI achieved.

There was significantly higher P2Y12 response unit values observed in the presence of elevated fibrinogen levels (205±80.4 vs. 169±90.3, p=0.015), diabetes mellitus (191.1±84.7 vs. 156.8±91.8, p=0.022) and increased body mass index (191.1±84.7 vs. 156.8±91.8, p=0.022). Among patients with diabetes, elevated fibrinogen levels was associated with lower PI (p=0.024) while higher BMI regardless of fibrinogen levels or diabetes mellitus was associated with lower PI (p=0.026). The adjusted PI was significantly reduced among diabetic patients with elevated fibrinogen compared with diabetic patients without elevated fibrinogen levels (23.9±3.9% vs. 45.1±4.5%, p<0.001). However no differences were observed in PI among non-diabetic patients with and without elevated fibrinogen levels (p=0.244). The adjusted PI was significantly lower for patients with elevated BMI compared to those without elevated BMI (36.8±9% vs. 49±7%).

The researchers of this study concluded that the presence of elevated fibrinogen (≥375 mg/dl), diabetes mellitus and high body mass index are all associated with lower PI with clopidogrel therapy among patients with cardiovascular disease.