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

J Am Coll Cardiol. 2006 Sep 5;48(5):931-8. doi: 10.1016/j.jacc.2006.04.090. Epub 2006 Aug 17.

Abstract

Objectives: 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.

Publication types

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

MeSH terms

  • Acute Disease
  • Adenosine Diphosphate / metabolism
  • Aged
  • Biomarkers / analysis
  • Clopidogrel
  • Dose-Response Relationship, Drug
  • Electrocardiography
  • Female
  • Humans
  • Inflammation
  • Male
  • Middle Aged
  • Myocardial Infarction / prevention & control*
  • Myocardium / pathology
  • Necrosis
  • Platelet Aggregation / drug effects
  • Platelet Aggregation Inhibitors / administration & dosage*
  • Single-Blind Method
  • Ticlopidine / administration & dosage
  • Ticlopidine / analogs & derivatives*
  • Troponin I / analysis

Substances

  • Biomarkers
  • Platelet Aggregation Inhibitors
  • Troponin I
  • Adenosine Diphosphate
  • Clopidogrel
  • Ticlopidine