Prasugrel compared with high loading- and maintenance-dose clopidogrel in patients with planned percutaneous coronary intervention: the Prasugrel in Comparison to Clopidogrel for Inhibition of Platelet Activation and Aggregation-Thrombolysis in Myocardial Infarction 44 trial

Circulation. 2007 Dec 18;116(25):2923-32. doi: 10.1161/CIRCULATIONAHA.107.740324. Epub 2007 Dec 3.


Background: The increasing use of higher-than-approved doses of clopidogrel in clinical practice is based in part on the desire for greater levels of inhibition of platelet aggregation (IPA). Prasugrel is a new thienopyridine that is more potent than standard-dose clopidogrel in healthy subjects and patients with stable coronary artery disease. The relative antiplatelet effects of prasugrel versus high-dose clopidogrel in percutaneous coronary intervention patients are unknown.

Methods and results: Prasugrel in Comparison to Clopidogrel for Inhibition of Platelet Activation and Aggregation-Thrombolysis in Myocardial Infarction 44 (PRINCIPLE-TIMI 44) was a randomized, double-blind, 2-phase crossover study of prasugrel compared with high-dose clopidogrel in patients undergoing cardiac catheterization for planned percutaneous coronary intervention. The primary end point of the loading-dose phase (prasugrel 60 mg versus clopidogrel 600 mg) was IPA with 20 mumol/L ADP at 6 hours. Patients with percutaneous coronary intervention entered the maintenance-dose phase, a 28-day crossover comparison of prasugrel 10 mg/d versus clopidogrel 150 mg/d with a primary end point of IPA after 14 days of either drug. In this study, 201 subjects were randomized. IPA at 6 hours was significantly higher in subjects receiving prasugrel (mean+/-SD, 74.8+/-13.0%) compared with clopidogrel (31.8+/-21.1%; P<0.0001). During the maintenance-dose phase, IPA with 20 mumol/L ADP was higher in subjects receiving prasugrel (61.3+/-17.8%) compared with clopidogrel (46.1+/-21.3%; P<0.0001). Results were consistent across all key secondary end points; significant differences emerged by 30 minutes and persisted across all time points.

Conclusions: Among patients undergoing cardiac catheterization with planned percutaneous coronary intervention, loading with 60 mg prasugrel resulted in greater platelet inhibition than a 600-mg clopidogrel loading dose. Maintenance therapy with prasugrel 10 mg/d resulted in a greater antiplatelet effect than 150 mg/d clopidogrel.

Publication types

  • Clinical Trial, Phase II
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Angioplasty, Balloon, Coronary
  • Clopidogrel
  • Combined Modality Therapy
  • Cross-Over Studies
  • Female
  • Humans
  • Male
  • Middle Aged
  • Myocardial Infarction / drug therapy*
  • Piperazines / administration & dosage*
  • Piperazines / pharmacokinetics
  • Platelet Activation / drug effects*
  • Platelet Aggregation Inhibitors / administration & dosage*
  • Platelet Aggregation Inhibitors / pharmacokinetics
  • Prasugrel Hydrochloride
  • Thiophenes / administration & dosage*
  • Thiophenes / pharmacokinetics
  • Thrombolytic Therapy / methods*
  • Ticlopidine / administration & dosage
  • Ticlopidine / analogs & derivatives*
  • Ticlopidine / pharmacokinetics
  • Treatment Outcome


  • Piperazines
  • Platelet Aggregation Inhibitors
  • Thiophenes
  • Clopidogrel
  • Prasugrel Hydrochloride
  • Ticlopidine