Effect of clopidogrel with and without eptifibatide on tumor necrosis factor-alpha and C-reactive protein release after elective stenting: results from the CLEAR PLATELETS 1b study.
OBJECTIVE
This study was performed to compare the effects of antiplatelet regimens on early inflammation and cardiac marker release after elective stenting.


BACKGROUND
Few data exist regarding the comparative effects of specific antiplatelet regimens on early inflammation marker release after stenting.


METHODS
In a 2 x 2 factorial randomized investigation, patients undergoing stenting were treated with either clopidogrel alone (300 mg or 600 mg; n = 60) or clopidogrel with eptifibatide (n = 60). Platelet aggregation (5 and 20 muM adenosine diphosphate [ADP]), ADP-stimulated expression of active glycoprotein (GP) IIb/IIIa, and platelet-bound P-selectin, tumor necrosis factor (TNF)-alpha, C-reactive protein (CRP), and cardiac markers were measured.


RESULTS
Compared with a strategy of clopidogrel alone, clopidogrel + eptifibatide reduced the release of cardiac markers. A marked reduction in platelet aggregation and active GP IIb/IIIa expression (p < or = 0.001) with clopidogrel + eptifibatide was associated with a decrease in CRP and TNF-alpha release (p < or = 0.001).


CONCLUSIONS
A strategy of clopidogrel with GP IIb/IIIa blockade resulted in superior inhibition of inflammation and cardiac marker release, which was accompanied by superior platelet inhibition immediately after percutaneous coronary intervention compared with a strategy of clopidogrel alone. The mechanistic and clinical implications of attenuated periprocedural inflammation and myocardial necrosis with a strategy of GP IIb/IIIa inhibition warrant further investigation.
Gurbel
Paul A
PA
Sinai Center for Thrombosis Research, Baltimore, Maryland 21215, USA. pgurbel@lifebridgehealth.org
Bliden
Kevin P
KP
Tantry
Udaya S
US
D000368:Aged; D015415:Biomarkers / Q000097:blood; D001792:Blood Platelets / Q000187:drug effects; D002097:C-Reactive Protein / Q000378:metabolism*; D000077144:Clopidogrel; D052279:Creatine Kinase, MB Form / Q000097:blood; D000077542:Eptifibatide; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000097:blood / Q000473:pathology / Q000628:therapy*; D009206:Myocardium / Q000473:pathology; D009336:Necrosis; D019007:P-Selectin / Q000097:blood; D010455:Peptides / Q000627:therapeutic use*; D010974:Platelet Aggregation; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors / Q000378:metabolism; D015607:Stents; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000097:blood*
D015415:Biomarkers; D019007:P-Selectin; D010455:Peptides; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein; D000077144:Clopidogrel; D052279:Creatine Kinase, MB Form; D000077542:Eptifibatide; D013988:Ticlopidine