title: Onset and extent of platelet inhibition by clopidogrel loading in patients undergoing elective coronary stenting: the Plavix Reduction Of New Thrombus Occurrence (PRONTO) trial.
abstract: BACKGROUND
  Despite the common practice of clopidogrel loading for coronary stenting, the time dependence and degree of platelet inhibition after this therapy are not well defined. We sought to establish an optimal clopidogrel dosing regimen for sustained platelet inhibition in stented patients.
  
  
  RESULTS
  Platelets were assessed by conventional aggregation with 5 micromol/L adenosine diphosphate (ADP), 1 microg/mL collagen (COLL), and 750 micromol/L arachidonic acid; whole blood aggregation by 1 microg/mL collagen (WBA); shear-induced closure time (CT); contractile force (CF); and expression of 9 surface receptors by flow cytometry in 100 patients undergoing elective stent placement without glycoprotein (GP) IIb/IIIa receptor antagonists. Blood was obtained at baseline and serially over 5 days poststenting after different clopidogrel loading regimens: 300 mg 24 hours before (Group A), 12 hours before (Group B), 3 to 6 hours before (Group C), and 75 mg at the time of intervention (Group D). Before stenting, ADP, COLL, CT, and WBA were reduced by clopidogrel loading (P <.05). CF was not affected by clopidogrel. Before stenting, GP IIb/IIIa expression increased in groups A through C (P <.05), whereas PECAM-1 and CD107a were reduced (P <.05). At 2 hours and 2 days poststenting, platelets, in general, exhibited an increase in activity that was most inhibited by clopidogrel loading. Clopidogrel inhibited GP Ib, platelet/endothelial cell adhesion molecule-1, CD 107a, CD 151, and GP IIb/IIIa expression at day 5 poststenting.
  
  
  CONCLUSIONS
  A 300 mg clopidogrel load given 3 to 24 hours before stenting inhibits platelets at the time of the procedure and reduces poststent activity more than a 75 mg dose given at the time of the procedure. The inhibition of adhesive molecule expression may also contribute an antithrombotic effect. Poststent activation of platelets may warrant higher periprocedural dosing.
authors.affiliation: Sinai Center for Thrombosis Research, Sinai Hospital of Baltimore, Baltimore, MD 21215-5271, USA. Pgurbel@lifebridgehealth.org
authors.forename: Paul A
authors.initials: PA
authors.lastname: Gurbel
authors.forename: Charles C
authors.initials: CC
authors.lastname: Cummings
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Bell
authors.forename: Amanda B
authors.initials: AB
authors.lastname: Alford
authors.forename: Andrew F
authors.initials: AF
authors.lastname: Meister
authors.forename: Victor L
authors.initials: VL
authors.lastname: Serebruany
mesh_terms: D000368:Aged; D015906:Angioplasty, Balloon, Coronary; D015703:Antigens, CD / Q000097:blood; D000077144:Clopidogrel; D003094:Collagen / Q000494:pharmacology; D003327:Coronary Disease; D003328:Coronary Thrombosis / Q000209:etiology / Q000517:prevention & control*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism; D016037:Single-Blind Method; D015607:Stents / Q000009:adverse effects*; D060185:Tetraspanin 24; D013988:Ticlopidine / Q000008:administration & dosage* / Q000031:analogs & derivatives
chemical_list: D015703:Antigens, CD; C554715:CD151 protein, human; D010975:Platelet Aggregation Inhibitors; D010980:Platelet Membrane Glycoproteins; D060185:Tetraspanin 24; D003094:Collagen; D000077144:Clopidogrel; D013988:Ticlopidine