Study design and rationale of a comparison of prasugrel and clopidogrel in medically managed patients with unstable angina/non-ST-segment elevation myocardial infarction: the TaRgeted platelet Inhibition to cLarify the Optimal strateGy to medicallY manage Acute Coronary Syndromes (TRILOGY ACS) trial

Am Heart J. 2010 Jul;160(1):16-22.e1. doi: 10.1016/j.ahj.2010.04.022.

Abstract

Practice guidelines recommend dual antiplatelet therapy with aspirin and clopidogrel for patients with non-ST-segment elevation acute coronary syndromes (NSTE ACS) regardless of in-hospital management strategy. Prasugrel-a thienopyridine adenosine diphosphate receptor antagonist that provides higher and less variable levels of platelet inhibition than clopidogrel-has demonstrated benefit when used to treat ACS patients undergoing percutaneous coronary intervention. However, the optimal approach to antiplatelet therapy for high-risk, medically managed NSTE ACS patients remains uncertain, as these patients have not been the focus of previous clinical trials of these therapies. TRILOGY ACS is a phase 3, randomized, double-blind trial enrolling approximately 10,300 NSTE ACS patients within 10 days of presentation with either unstable angina or NSTE myocardial infarction who are not intended to undergo revascularization procedures for their index event. Patients will be randomly allocated to prasugrel + aspirin versus clopidogrel + aspirin for a median duration of 18 months. A reduction in the maintenance dose of prasugrel for elderly patients (age >or=75 years) and those with body weight <60 kg is planned. The primary composite efficacy end point will be time to first occurrence of cardiovascular death, myocardial infarction, or stroke in patients aged <75 years. If the superiority of prasugrel is established in patients aged <75 years, the treatment arms will then be compared for all subjects (including those aged >or=75 years). TRILOGY ACS is the largest randomized clinical trial to date focusing exclusively on medically managed NSTE ACS patients and will provide important information regarding the optimal approach to oral antiplatelet therapy for this high-risk, understudied population.

Trial registration: ClinicalTrials.gov NCT00699998.

Publication types

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

MeSH terms

  • Administration, Oral
  • Aged
  • Angina, Unstable / drug therapy*
  • Angina, Unstable / mortality
  • Angina, Unstable / physiopathology
  • Clopidogrel
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Therapy, Combination
  • Electrocardiography*
  • Follow-Up Studies
  • Global Health
  • Humans
  • Middle Aged
  • Myocardial Infarction / drug therapy*
  • Myocardial Infarction / mortality
  • Myocardial Infarction / physiopathology
  • Piperazines / administration & dosage
  • Piperazines / therapeutic use*
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Prasugrel Hydrochloride
  • Purinergic P2 Receptor Antagonists
  • Survival Rate
  • Thiophenes / administration & dosage
  • Thiophenes / therapeutic use*
  • Ticlopidine / administration & dosage
  • Ticlopidine / analogs & derivatives*
  • Ticlopidine / therapeutic use
  • Time Factors
  • Treatment Outcome

Substances

  • Piperazines
  • Platelet Aggregation Inhibitors
  • Purinergic P2 Receptor Antagonists
  • Thiophenes
  • Clopidogrel
  • Prasugrel Hydrochloride
  • Ticlopidine

Associated data

  • ClinicalTrials.gov/NCT00699998