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

• Published in: Journal of the American College of Cardiology Vol. 52; no. 13; pp. 1052 - 1059
• Main Authors: Ang, Lawrence, Palakodeti, Vachaspathi, Khalid, Ahmer, Tsimikas, Sotirios, Idrees, Zaheib, Tran, Phillip, Clopton, Paul, Zafar, Nayab, Bromberg-Marin, Guilherme, Keramati, Shahin, Mahmud, Ehtisham
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 23.09.2008; Elsevier Limited
• Subjects: Aged; Blood; Body Mass Index; Cardiology; Cardiovascular; Cardiovascular Diseases - complications; Cardiovascular Diseases - drug therapy; Cardiovascular Diseases - metabolism; clopidogrel; Diabetes Complications - drug therapy; Diabetes Complications - metabolism; Diabetes Complications - physiopathology; diabetes mellitus; Female; fibrinogen; Fibrinogen - metabolism; Heart attacks; Humans; Internal Medicine; Laboratories; Male; Middle Aged; platelet aggregation; Platelet Aggregation - drug effects; Platelet Aggregation Inhibitors - pharmacology; Platelet Aggregation Inhibitors - therapeutic use; Platelet Function Tests; Prospective Studies; Ticlopidine - analogs & derivatives; Ticlopidine - pharmacology; Ticlopidine - therapeutic use; United States > US; California; clopidogrel; CRP; fibrinogen; body mass index; DM; GP; diabetes mellitus; platelet aggregation; CVD; PRU; PCI; LTA; PI; BMI; cardiovascular disease; platelet inhibition; C-reactive protein; light transmittance aggregometry; percutaneous coronary intervention; P2Y12 response units; glycoprotein
• ISSN: 0735-1097; 1558-3597; 1558-3597
• DOI: 10.1016/j.jacc.2008.05.054

Elevated Plasma Fibrinogen and Diabetes Mellitus Are Associated With Lower Inhibition of Platelet Reactivity With Clopidogrel Lawrence Ang, Vachaspathi Palakodeti, Ahmer Khalid, Sotirios Tsimikas, Zaheib Idrees, Phillip Tran, Paul Clopton, Nayab Zafar, Guilherme Bromberg-Marin, Shahin Keramati, Ehtisham Mahmud A heterogeneous platelet reactivity response to clopidogrel exists. In this study, platelet reactivity was measured in 157 subjects (age 67.2 ± 12.2 years; 59.9% men) with cardiovascular disease utilizing a rapid platelet function assay. Among variables known to affect platelet reactivity, elevated plasma fibrinogen (≥375 mg/dl), diabetes mellitus, and increased body mass index (BMI) (≥25 kg/m2) were associated with lower platelet inhibition (PI) with clopidogrel. After testing for interaction, significantly lower PI was observed only in diabetic patients with elevated plasma fibrinogen (≥375 mg/dl) while increased BMI (≥25 kg/m2) remained independently associated with lower PI regardless of diabetic status or fibrinogen level. The goal of this study was to identify factors associated with lower platelet inhibition (PI) with clopidogrel in subjects with cardiovascular disease (CVD). A heterogeneous platelet reactivity response to clopidogrel exists, and the clinical or biochemical predictors of suboptimal PI with clopidogrel remain unclear. 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. 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). 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.