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CLINICAL RESEARCH: INTERVENTIONAL CARDIOLOGY

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

Sinai Center for Thrombosis Research, Baltimore, Maryland.

Manuscript received October 20, 2005; revised manuscript received December 14, 2005, accepted December 19, 2005.

^_* Reprint requests and correspondence: Dr. Paul A. Gurbel, Sinai Center for Thrombosis Research, Hoffberger Building, Suite 56, 2401 W. Belvedere Avenue, Baltimore, Maryland 21215. (Email: pgurbel{at}lifebridgehealth.org).

OBJECTIVES: 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 µM adenosine diphosphate [ADP]), ADP-stimulated expression of active glycoprotein (GP) IIb/IIIa, and platelet-bound P-selectin, tumor necrosis factor (TNF)-, 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 0.001) with clopidogrel + eptifibatide was associated with a decrease in CRP and TNF- release (p 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.

Abbreviations and Acronyms   ADP = adenosine diphosphate   CK = creatinine kinase   CLEAR PLATELETS = Clopidogrel Loading With Eptifibatide to Arrest the Reactivity of Platelets   CRP = C-reactive protein   ELISA = enzyme-linked immunosorbent assay   GP IIb/IIIa = glycoprotein IIb/IIIa   MFI = mean fluorescence intensity   PCI = percutaneous coronary intervention   TNF = tumor necrosis factor

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