title: 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.
abstract: 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.
  
  
  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.
authors.affiliation: Sinai Center for Thrombosis Research, Hoffberger Bldg, Suite 56, 2401 W Belvedere Ave, Baltimore, MD 21215, USA. pgurbel@lifebridgehealth.org
authors.forename: Paul A
authors.initials: PA
authors.lastname: Gurbel
authors.forename: Kevin P
authors.initials: KP
authors.lastname: Bliden
authors.forename: Kazi A
authors.initials: KA
authors.lastname: Zaman
authors.forename: Jason A
authors.initials: JA
authors.lastname: Yoho
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Hayes
authors.forename: Udaya S
authors.initials: US
authors.lastname: Tantry
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000787:Angina Pectoris / Q000209:etiology; D015906:Angioplasty, Balloon, Coronary; D002317:Cardiovascular Agents / Q000627:therapeutic use; D000077144:Clopidogrel; D023921:Coronary Stenosis / Q000097:blood / Q000150:complications / Q000503:physiopathology / Q000628:therapy; D003328:Coronary Thrombosis / Q000517:prevention & control; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D000077542:Eptifibatide; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000209:etiology; D009206:Myocardium / Q000473:pathology; D009336:Necrosis; D010455:Peptides / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors; D011292:Premedication; D012307:Risk Factors; D015607:Stents; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D002317:Cardiovascular Agents; D010455:Peptides; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D000077144:Clopidogrel; D000077542:Eptifibatide; D013988:Ticlopidine