Clopidogrel-mediated reduction of circulating tissue factor in patients with stable coronary artery disease.
BACKGROUND
Tissue factor (TF), the initiator of coagulation, circulates in blood and contributes to thrombosis in patients with coronary artery disease (CAD). TF is present in the alpha-granules of platelets. Therapy with clopidogrel results in inhibition of platelet degranulation. Whether clopidogrel affects circulating TF is unknown. This study examined the effect of clopidogrel on TF level in the blood of patients with stable CAD and ST-elevation myocardial infarction (STEMI) as well as healthy controls.


METHODS
Thirty-three patients with CAD and twenty with STEMI were studied pre and post clopidogrel therapy (loading dose 300 mg, then 75 mg daily). All were treated with aspirin 100 mg/d. The control groups consisted of thirty healthy male volunteers also treated with clopidogrel and ten patients with CAD treated with aspirin only. TF concentration in blood drawn pre and 96 h post clopidogrel administration was measured by enzyme-linked immunosorbent assay.


RESULTS
Patients with CAD and STEMI had significantly more TF in blood than healthy controls. Clopidogrel reduced TF in stable CAD patients to levels seen in healthy controls. No alterations in TF were found in controls and patients with STEMI post clopidogrel therapy. Clopidogrel reduced sCD40L level in stable CAD patients, but not in STEMI patients. A correlation between TF and sCD40L was found for the combined CAD and control, but not STEMI group.


CONCLUSIONS
Clopidogrel leads to a reduction of not only sCD40L but also TF in stable CAD. The reduction of TF may lead to a reduced thrombogenicity, contributing to the benefits of clopidogrel therapy.
Stellbaum
C
C
Department of Cardiology and Pneumology, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany.
Willich
T
T
Boltzen
U
U
Ayral
Y
Y
Szotowski
B
B
Piorkowski
M
M
Schultheiss
H-P
HP
Rauch
U
U
D000328:Adult; D023201:CD40 Ligand / Q000097:blood / Q000187:drug effects*; D000077144:Clopidogrel; D003324:Coronary Artery Disease / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy / Q000473:pathology; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage; D012995:Solubility; D013925:Thromboplastin / Q000032:analysis / Q000378:metabolism*; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D016896:Treatment Outcome
D010975:Platelet Aggregation Inhibitors; D023201:CD40 Ligand; D013925:Thromboplastin; D000077144:Clopidogrel; D013988:Ticlopidine