Elevated plasma fibrinogen and diabetes mellitus are associated with lower inhibition of platelet reactivity with clopidogrel.
OBJECTIVE
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 > or =7 days or 600-mg bolus > or =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 (> or =375 mg/dl), diabetes mellitus, and increased body mass index (BMI) (> or =25 kg/m(2)). 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 (> or =375 mg/dl) in the presence of diabetes mellitus and increased BMI (> or =25 kg/m(2)) are associated with lower PI with clopidogrel in patients with CVD.
Ang
Lawrence
L
Division of Cardiovascular Medicine, University of California, San Diego School of Medicine, San Diego, California, USA.
Palakodeti
Vachaspathi
V
Khalid
Ahmer
A
Tsimikas
Sotirios
S
Idrees
Zaheib
Z
Tran
Phillip
P
Clopton
Paul
P
Zafar
Nayab
N
Bromberg-Marin
Guilherme
G
Keramati
Shahin
S
Mahmud
Ehtisham
E
D000368:Aged; D015992:Body Mass Index; D002318:Cardiovascular Diseases / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D000077144:Clopidogrel; D048909:Diabetes Complications / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D005260:Female; D005340:Fibrinogen / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D010979:Platelet Function Tests; D011446:Prospective Studies; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
D010975:Platelet Aggregation Inhibitors; D005340:Fibrinogen; D000077144:Clopidogrel; D013988:Ticlopidine