Clopidogrel Loading With Eptifibatide to Arrest the Reactivity of Platelets Study - CLEAR PLATELETS
The goal of the study was to evaluate use of eptifibatide and clopidogrel on platelet inhibition and myocardial necrosis among patients undergoing elective stenting.
Patients Enrolled: 120
Mean Follow Up: 24 hours
Undergoing elective coronary stenting and age >18 years
History of bleeding diathesis, acute MI within 48 hours, elevated cardiac markers above upper limits of normal, cerebrovascular event within three months, chronic vessel occlusion or angiographically visible thrombus, illicit drug or alcohol abuse, prothrombin time >1.5 times control, platelet count <100,000/mm3, hematocrit <30%, creatinine >4.0 mg/dl, and thienopyridine or GP IIb/IIIa use before the procedure
Patients were randomized in a factorial design to 300 mg clopidogrel with (n=30) or without eptifibatide (n=30) or 600 mg clopidogrel with (n=30) or without eptifibatide (n=30). The clopidogrel loading dose was given to all patients immediately after stenting. All patients were also treated with clopidogrel 75 mg daily. Blood draws were taken at baseline and three, eight, and 18-24 hours after stenting.
Aspirin for seven days before the procedure and daily thereafter, and unfractionated heparin (60 U/kg bolus) immediately prior to stenting
The majority of patients in the trial underwent stenting due to stable angina (82%, n=98), while 18 patients had unstable angina and four had non-ST elevation myocardial infarction (MI). Patients were oldest in the clopidogrel 300 mg alone group (mean age 68 years), followed by the clopidogrel 600 mg plus eptifibatide group (64 years), clopidogrel 300 mg plus eptifibatide group (58 years), and clopidogrel 600 mg alone group (55 years). The majority of patients were stented for de novo lesions (90%).
Clinical events were rare, with no in-hospital deaths, strokes, or heart failure, and one ST-segment elevation MI in the 300 mg clopidogrel alone group following a subacute thrombosis. There was one major bleed in each of the eptifibatide groups. Cardiac marker release was lower in the eptifibatide groups. Troponin elevation occurred in seven patients in the 300 mg alone group, four patients in the 600 mg alone group, two patients in the 300 mg plus eptifibatide group, and one patient in the 600 mg plus eptifibatide group (p=0.004 for clopidogrel alone vs. clopidogrel plus eptifibatide). Likewise, creatine kinase-MB was elevated in nine, seven, two, and one patients, respectively.
Platelet inhibition was higher in the 600 mg clopidogrel alone group compared with the 300 mg alone group. However, platelet inhibition was highest in the eptifibatide plus 600 mg clopidogrel group (by ≥2 times inhibition compared to the clopidogrel alone groups at each timepoint; p<0.001). Eptifibatide plus 300 mg clopidogrel also had higher inhibition by ≥2 times compared to the clopidogrel alone groups at each timepoint (p<0.001).
Among patients undergoing elective stenting, treatment with clopidogrel plus eptifibatide was associated with greater platelet inhibition and lower cardiac necrosis release compared with clopidogrel alone. Additionally, use of a 600 mg clopidogrel loading dose was associated with greater platelet inhibition compared with a 300 mg loading dose.
The present study was one of the first randomized trials to evaluate a 300 mg clopidogrel loading dose with a 600 mg clopidogrel loading dose. The factorial design also assessed the additional effect of eptifibatide on top of the two doses of clopidogrel. While the study showed a 600 mg loading dose of clopidogrel had greater platelet inhibition than a 300 mg loading dose, the greatest benefit was observed with the addition of eptifibatide to either dose of clopidogrel.
Unlike the present study, the ISAR REACT study showed no benefit of a glycoprotein (GP) IIb/IIIa inhibitor (abciximab) on top of treatment with 600 mg clopidogrel alone. The difference was likely due to the timing of the clopidogrel administration, which was a median of 7.4 hours prior to percutaneous coronary intervention (PCI) in ISAR REACT and was immediately following PCI in CLEAR PLATELETS. Additionally, patients in the CLEAR PLATELETS study were slightly higher risk.
Gurbel PA, Bliden KP, Zaman KA, Yoho JA, Hayes KM, Tantry US. Clopidogrel loading with eptifibatide to arrest the reactivity of platelets: results of the Clopidogrel Loading With Eptifibatide to Arrest the Reactivity of Platelets (CLEAR PLATELETS) study. Circulation 2005;111:1153-9.
Keywords: Myocardial Infarction, Stroke, Creatine Kinase, Platelet Aggregation Inhibitors, Angina, Stable, Coronary Disease, Ticlopidine, Blood Platelets, Immunoglobulin Fab Fragments, Percutaneous Coronary Intervention, Peptides, Thrombosis, Heart Failure, Troponin, Platelet Glycoprotein GPIIb-IIIa Complex
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