title: A randomized comparison of high clopidogrel loading doses in patients with non-ST-segment elevation acute coronary syndromes: the ALBION (Assessment of the Best Loading Dose of Clopidogrel to Blunt Platelet Activation, Inflammation and Ongoing Necrosis) trial.
abstract: OBJECTIVE
  We sought to compare the antiplatelet effects of three clopidogrel loading doses (LDs).
  
  
  BACKGROUND
  Administration of a 300-mg clopidogrel LD is beneficial in situations requiring rapid platelet inhibition. Whether higher LDs can provide further benefits remains unknown.
  
  
  METHODS
  Patients (n = 103) with non-ST-segment elevation acute coronary syndromes were randomized to receive a 300-mg, 600-mg, or 900-mg clopidogrel LD, given on top of other standard therapy (including acetylsalicylic acid). The main outcome measure was inhibition of adenosine diphosphate-induced inhibition of platelet aggregation (IPA); inhibition of platelet activation, inflammatory markers, troponin I release, and major adverse cardiac events also were evaluated; all measures were blindly evaluated.
  
  
  RESULTS
  Compared with the 300-mg LD, greater doses were associated with significantly greater platelet inhibition, with dose-effect relationships observed for onset of action, maximal plateau, 24-h areas under the curves of IPA, and rates of low IPA (<10% at 6 h), using 20 micromol/l major adverse cardiac events. A significant dose-response was also observed for the vasodilator-stimulated phosphoprotein index, a measure of P2Y(12) receptor inhibition. Similar but nonsignificant trends were observed for troponin release and major adverse cardiac events. Bleeding rates were similar in each group.
  
  
  CONCLUSIONS
  In low-to-moderate risk patients with non-ST-elevation acute coronary syndromes, clopidogrel LDs >300 mg provide a faster onset of action, a higher IPA plateau, and greater reductions in platelet activation during the first 24 h. A 900-mg LD may induce a greater antiplatelet effect than 600 mg, when compared with the standard 300-mg regimen. These findings require further clinical confirmation.
authors.affiliation: Institut de Cardiologie-Pitié-Salpêtriére University Hospital, Assistence Publique Hôpiteux de Paris (APHP), Paris, France. gilles.montalescot@psl.aphp.fr
authors.forename: Gilles
authors.initials: G
authors.lastname: Montalescot
authors.forename: Georges
authors.initials: G
authors.lastname: Sideris
authors.forename: Catherine
authors.initials: C
authors.lastname: Meuleman
authors.forename: Claire
authors.initials: C
authors.lastname: Bal-dit-Sollier
authors.forename: Nicolas
authors.initials: N
authors.lastname: Lellouche
authors.forename: Ph Gabriel
authors.initials: PG
authors.lastname: Steg
authors.forename: Michel
authors.initials: M
authors.lastname: Slama
authors.forename: Olivier
authors.initials: O
authors.lastname: Milleron
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Collet
authors.forename: Patrick
authors.initials: P
authors.lastname: Henry
authors.forename: Farzin
authors.initials: F
authors.lastname: Beygui
authors.forename: Ludovic
authors.initials: L
authors.lastname: Drouet
mesh_terms: D000208:Acute Disease; D000244:Adenosine Diphosphate / Q000378:metabolism; D000368:Aged; D015415:Biomarkers / Q000032:analysis; D000077144:Clopidogrel; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography; D005260:Female; D006801:Humans; D007249:Inflammation; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000517:prevention & control*; D009206:Myocardium / Q000473:pathology; D009336:Necrosis; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D016037:Single-Blind Method; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D019210:Troponin I / Q000032:analysis
chemical_list: D015415:Biomarkers; D010975:Platelet Aggregation Inhibitors; D019210:Troponin I; D000244:Adenosine Diphosphate; D000077144:Clopidogrel; D013988:Ticlopidine