Effects of combined therapy with clopidogrel and acetylsalicylic acid on platelet glycoprotein expression and aggregation.
This study aimed to compare the effects of clopidogrel, acetylsalicylic acid (ASA), and the combination of both substances on platelet aggregation and expression of platelet membrane glycoproteins in patients with chronic coronary artery disease. We investigated platelet activation by flow cytometry and by platelet aggregation and disaggregation in 60 patients randomly assigned to 3 treatment groups: ASA, clopidogrel, combination of clopidogrel and ASA, treated for 14 days. Adenosine diphosphate (ADP)-induced expression of P-selectin and of PAC-1 was significantly reduced after 2 wk of clopidogrel but not of ASA treatment. Treatment with clopidogrel reduced the ADP-induced platelet aggregation. The combination of clopidogrel and ASA did not increase the inhibition of platelet activation compared with clopidogrel alone. A significant increase in platelet disaggregation was observed with clopidogrel alone and was more pronounced with the combination of clopidogrel and ASA. ADP-induced platelet degranulation, activation of GPIIb/IIIa receptor, and aggregation in vivo are effectively inhibited by clopidogrel. The significantly increased disaggregation under clopidogrel and ASA suggests that the combined therapy may be superior to the monotherapy in patients with coronary artery disease and a high risk for vascular events.
Dörr
Gesine
G
Department of Medicine/Cardiology, Charité, Campus Virchow Klinikum, Humboldt Universität Berlin, Augustenburgerplatz 1, D-13353 Berlin, Germany. gesine.doerr@charite.de
Schmidt
Gunter
G
Gräfe
Michael
M
Regitz-Zagrosek
Vera
V
Fleck
Eckart
E
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000368:Aged; D001241:Aspirin / Q000627:therapeutic use*; D000077144:Clopidogrel; D003327:Coronary Disease / Q000097:blood / Q000188:drug therapy*; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D054641:Dual Specificity Phosphatase 2; D005260:Female; D006801:Humans; D008297:Male; D019007:P-Selectin / Q000378:metabolism; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism*; D011446:Prospective Studies; D054648:Protein Phosphatase 2; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D013988:Ticlopidine / Q000031:analogs & derivatives / Q000627:therapeutic use*
D019007:P-Selectin; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D000244:Adenosine Diphosphate; D000077144:Clopidogrel; D054648:Protein Phosphatase 2; C517032:DUSP2 protein, human; D054641:Dual Specificity Phosphatase 2; D017027:Protein Tyrosine Phosphatases; D013988:Ticlopidine; D001241:Aspirin