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

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 × 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)-α, 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-α 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.