Clopidogrel 600-mg double loading dose achieves stronger platelet inhibition than conventional regimens: results from the PREPAIR randomized study

J Am Coll Cardiol. 2008 Mar 18;51(11):1066-72. doi: 10.1016/j.jacc.2007.12.013.

Abstract

Objectives: The objective of this study was to compare the level of platelet inhibition achieved by 3 different clopidogrel loading regimens in patients undergoing elective angiography and percutaneous coronary intervention when appropriate.

Background: Optimal platelet inhibition is a key therapeutic goal for patients undergoing percutaneous coronary intervention. Although 600 mg has been described as the maximum absorbed dose when given as a single bolus, the effects of 2 boluses given 24 h apart have not been described.

Methods: Patients (n = 148) were randomly assigned to one of 3 regimens: Group A, clopidogrel 300 mg the day before (>or=15 h) + 75 mg the morning of the procedure; Group B, clopidogrel 600 mg the morning of the procedure (>or=2 h); and Group C, clopidogrel 600 mg the day before (>or=15 h) and 600 mg the morning of the procedure (>or=2 h). Blood samples were obtained at baseline and immediately before angiography. Peak and late platelet aggregation were measured in platelet rich plasma, with researchers blinded to treatment allocation.

Results: There was a consistent difference favoring Group C in all aggregation parameters. Percent inhibition in Groups A, B, and C was 31.4%, 29.0%, and 49.5%, respectively, for peak aggregation (5 micromol/l adenosine diphosphate; p < 0.0001) and 54.1%, 57.7%, and 81.1%, respectively, for late aggregation (p < 0.0001). Similar striking reductions were observed when 20 micromol/l adenosine diphosphate was used. All comparisons between Group C and the other 2 groups were statistically significant, and those between Groups A and B were not.

Conclusions: Clopidogrel 600-mg double bolus achieves greater platelet inhibition than conventional single loading doses.

Publication types

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

MeSH terms

  • Aged
  • Angioplasty, Balloon, Coronary*
  • Blood Platelets / drug effects
  • Clopidogrel
  • Coronary Angiography
  • Coronary Artery Disease / therapy
  • Coronary Thrombosis / prevention & control*
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Female
  • Humans
  • Injections, Intravenous
  • Male
  • Middle Aged
  • Platelet Aggregation Inhibitors / administration & dosage*
  • Ticlopidine / administration & dosage
  • Ticlopidine / analogs & derivatives*
  • Treatment Outcome

Substances

  • Platelet Aggregation Inhibitors
  • Clopidogrel
  • Ticlopidine