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...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.展开更多
High platelet reactivity (HPR) and suboptimal response to dual antiplatelet therapy (DAPT) may explain high recurrent rates of ischemic events in Type II diabetes mellitus (DM) patients undergoing percutaneous coronar...High platelet reactivity (HPR) and suboptimal response to dual antiplatelet therapy (DAPT) may explain high recurrent rates of ischemic events in Type II diabetes mellitus (DM) patients undergoing percutaneous coronary intervention (PCI). The aim of this study was to examine the effect of clopidogrel on platelet reactivity, and thrombogenecity between DM and non-DM PCI-treated patients (n = 138). Patients were categorized according to clopidogrel treatment and DM status. Patients received a maintenance-dose clopidogrel of 75 mg/d (C75 group, n = 72) or a 600 mg clopidogrel loading-dose in clopidogrel na?ve patients (C600 group, n = 66). Platelet function was assessed by thrombelastography, flow cytometry, VerifyNowTM aspirin assay and light transmittance aggregometry (LTA). Aspirin response was similar between treatments and DM status. In the C75 group, DM patients had higher 5 and 20 μM ADP-, 2 μg/ml collagen-induced LTA;and p-selectin expression compared to non-DM patients (p ≤ 0.05 for all). DM patients in the C600 group had higher 5 and 20 μM ADP-induced LTA post dosing (p p 12 receptor antagonists.展开更多
文摘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.
文摘High platelet reactivity (HPR) and suboptimal response to dual antiplatelet therapy (DAPT) may explain high recurrent rates of ischemic events in Type II diabetes mellitus (DM) patients undergoing percutaneous coronary intervention (PCI). The aim of this study was to examine the effect of clopidogrel on platelet reactivity, and thrombogenecity between DM and non-DM PCI-treated patients (n = 138). Patients were categorized according to clopidogrel treatment and DM status. Patients received a maintenance-dose clopidogrel of 75 mg/d (C75 group, n = 72) or a 600 mg clopidogrel loading-dose in clopidogrel na?ve patients (C600 group, n = 66). Platelet function was assessed by thrombelastography, flow cytometry, VerifyNowTM aspirin assay and light transmittance aggregometry (LTA). Aspirin response was similar between treatments and DM status. In the C75 group, DM patients had higher 5 and 20 μM ADP-, 2 μg/ml collagen-induced LTA;and p-selectin expression compared to non-DM patients (p ≤ 0.05 for all). DM patients in the C600 group had higher 5 and 20 μM ADP-induced LTA post dosing (p p 12 receptor antagonists.
