A randomized trial of prasugrel versus clopidogrel in patients with high platelet reactivity on clopidogrel after elective percutaneous coronary intervention with implantation of drug-eluting stents: results of the TRIGGER-PCI (Testing Platelet Reactivity In Patients Undergoing Elective Stent Placement on Clopidogrel to Guide Alternative Therapy With Prasugrel) study

J Am Coll Cardiol. 2012 Jun 12;59(24):2159-64. doi: 10.1016/j.jacc.2012.02.026. Epub 2012 Apr 18.

Abstract

Objectives: This study sought to investigate the efficacy, safety, and antiplatelet effect of prasugrel as compared with clopidogrel in patients with high on-treatment platelet reactivity (HTPR) after elective percutaneous coronary intervention (PCI).

Background: The extent to which prasugrel can correct HTPR and improve clinical outcomes in patients undergoing elective PCI is unknown.

Methods: Stable coronary artery disease (CAD) patients with HTPR (>208 P2Y(12) reaction units [PRU] by the VerifyNow test) after elective PCI with at least 1 drug-eluting stent (DES) were randomly assigned to either prasugrel 10 mg daily or clopidogrel 75 mg daily. Platelet reactivity of the patients on the study drug was reassessed at 3 and 6 months. The study was stopped prematurely for futility because of a lower than expected incidence of the primary endpoint.

Results: In 212 patients assigned to prasugrel, PRU decreased from 245 (225 to 273) (median [interquartile range]) at baseline to 80 (42 to 124) at 3 months, whereas in 211 patients assigned to clopidogrel, PRU decreased from 249 (225 to 277) to 241 (194 to 275) (p < 0.001 vs. prasugrel). The primary efficacy endpoint of cardiac death or myocardial infarction at 6 months occurred in no patient on prasugrel versus 1 on clopidogrel. The primary safety endpoint of non-coronary artery bypass graft Thrombolysis In Myocardial Infarction major bleeding at 6 months occurred in 3 patients (1.4%) on prasugrel versus 1 (0.5%) on clopidogrel.

Conclusions: Switching from clopidogrel to prasugrel in patients with HTPR afforded effective platelet inhibition. However, given the low rate of adverse ischemic events after PCI with contemporary DES in stable CAD, the clinical utility of this strategy could not be demonstrated.

Trial registration: ClinicalTrials.gov NCT00910299.

Publication types

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

MeSH terms

  • Aged
  • Angioplasty, Balloon, Coronary*
  • Blood Platelets / drug effects*
  • Blood Platelets / physiology
  • Clopidogrel
  • Coronary Artery Disease / drug therapy
  • Female
  • Humans
  • Male
  • Middle Aged
  • Piperazines / administration & dosage
  • Piperazines / pharmacology*
  • Piperazines / therapeutic use*
  • Platelet Aggregation Inhibitors / pharmacology*
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Prasugrel Hydrochloride
  • Purinergic P2Y Receptor Antagonists / pharmacology*
  • Purinergic P2Y Receptor Antagonists / therapeutic use*
  • Thiophenes / administration & dosage
  • Thiophenes / pharmacology*
  • Thiophenes / therapeutic use*
  • Ticlopidine / administration & dosage
  • Ticlopidine / analogs & derivatives*
  • Ticlopidine / therapeutic use

Substances

  • Piperazines
  • Platelet Aggregation Inhibitors
  • Purinergic P2Y Receptor Antagonists
  • Thiophenes
  • Clopidogrel
  • Prasugrel Hydrochloride
  • Ticlopidine

Associated data

  • ClinicalTrials.gov/NCT00910299