Background -Pretreatment is not the most common strategy practiced for clopidogrel administration in elective coronary stenting. Moreover, limited information is available on the antiplatelet pharmacodynamics of a 300-mg versus a 600-mg clopidogrel loading dose, and the comparative effect of eptifibatide with these regimens is unknown. Methods and Results -Patients undergoing elective stenting (n=120) were enrolled in a 2X2 factorial study(300 mg clopidogrel with or without eptifibatide; 600 mg clopidogrel with or without eptifibatide)(Clopidogrel Loading With Eptifibatide to Arrest the Reactivity of Platelets[CLEAR PLATELETS] Study). Clopidogrel was administered immediately after stenting. Aggregometry and flow cytometry were used to assess platelet reactivity. Eptifibatide added a ≥2-fold increase in platelet inhibition to 600 mg clopidogrel alone at 3, 8, and 18 to 24 hours after stenting as measured by 5 μmol/L ADP-induced aggregation(P< 0.001). Without eptifibatide, 600 mg clopidogrel produced better inhibition than 300 mg clopidogrel at all time points(P< 0.001). Glycoprotein IIb/IIIa(GPIIb/IIIa) blockade was associated with lower cardiac marker release. Active GPIIb/IIIa expression was inhibited most in the groups treated with eptifibatide(P< 0.05). Conclusions -In elective stenting without clopidogrel pretreatment, use of a GPIIb/IIIa inhibitor produces superior platelet inhibition and lower myocardial necrosis compared with high-dose(600 mg) or standard-dose(300 mg) clopidogrel loading alone. In the absence of a GPIIb/IIIa inhibitor, 600 mg clopidogrel provides better platelet inhibition than the standard 300-mg dose. These results require confirmation in a large-scale clinical trial. Background -Pretreatment is not the most common strategy practiced for clopidogrel administration in elective coronary stenting. Moreover, limited information is available on the antiplatelet pharmacodynamics of a 300-mg versus a 600-mg clopidogrel loading dose, and the comparative effect of eptifibatide with these regimens is unknown. Methods and Results-Patients undergoing elective stenting (n = 120) were enrolled in a 2 × 2 factorial study (300 mg clopidogrel with or without eptifibatide; 600 mg clopidogrel with or without eptifibatide) (Clopidogrel Loading With Eptifibatide to Arrest the Reactivity of Platelets [CLEAR PLATELETS] Study. Clopidogrel was administered immediately after stenting. Aggregometry and flow cytometry were used to assess platelet reactivity. Eptifibatide added a ≧ 2-fold increase in platelet inhibition to 600 mg clopidogrel alone at 3, 8, and 18 to 24 hours after stenting as measured by 5 μmol / L ADP-induced aggregation (P <0.001). Without eptifibatide, 600 mg clop Glycoprotein IIb / IIIa (GPIIb / IIIa) blockade was associated with lower cardiac marker release. Active GPIIb / IIIa expression was inhibited most in the groups treated with eptifibatide (P <0.05) Conclusions-In elective stenting without clopidogrel pretreatment, use of a GPIIb / IIIa inhibitor produce superior platelet inhibition and lower myocardial necrosis compared with high-dose (600 mg) or standard-dose (300 mg) clopidogrel loading alone . The absence of a GPIIb / IIIa inhibitor, 600 mg clopidogrel provides better platelet inhibition than the standard 300-mg dose. These results require confirmation in a large-scale clinical trial.