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 Mar 8;111(9):1153-9. doi: 10.1161/01.CIR.0000157138.02645.11. Epub 2005 Feb 28.


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 > or =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 micromol/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.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Angina Pectoris / etiology
  • Angioplasty, Balloon, Coronary
  • Cardiovascular Agents / therapeutic use
  • Clopidogrel
  • Coronary Stenosis / blood
  • Coronary Stenosis / complications
  • Coronary Stenosis / physiopathology
  • Coronary Stenosis / therapy
  • Coronary Thrombosis / prevention & control
  • Dose-Response Relationship, Drug
  • Drug Synergism
  • Drug Therapy, Combination
  • Eptifibatide
  • Female
  • Humans
  • Male
  • Middle Aged
  • Myocardial Infarction / etiology
  • Myocardium / pathology
  • Necrosis
  • Peptides / administration & dosage
  • Peptides / pharmacology
  • Peptides / therapeutic use*
  • Platelet Aggregation / drug effects
  • Platelet Aggregation Inhibitors / administration & dosage
  • Platelet Aggregation Inhibitors / pharmacology
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Platelet Glycoprotein GPIIb-IIIa Complex / antagonists & inhibitors
  • Premedication
  • Risk Factors
  • Stents
  • Ticlopidine / administration & dosage
  • Ticlopidine / analogs & derivatives*
  • Ticlopidine / pharmacology
  • Ticlopidine / therapeutic use


  • Cardiovascular Agents
  • Peptides
  • Platelet Aggregation Inhibitors
  • Platelet Glycoprotein GPIIb-IIIa Complex
  • Clopidogrel
  • Eptifibatide
  • Ticlopidine