title: Clinical outcomes for prasugrel versus clopidogrel in patients with unstable angina or non-ST-elevation myocardial infarction: an analysis from the TRITON-TIMI 38 trial.
abstract: OBJECTIVE
  In the TRial to assess Improvement in Therapeutic Outcomes by optimizing platelet inhibitioN with prasugrel Thrombolysis In Myocardial Infarction 38 (TRITON-TIMI 38), prasugrel reduced the primary ischaemic endpoint as compared with clopidogrel in acute coronary syndrome (ACS) patients planned to undergo percutaneous coronary interventions, but increased the risk of bleeding. The present analysis shows the efficacy and safety data for the 10,074 non-ST segment elevation (NSTE)-ACS patients included in that trial.
  
  
  RESULTS
  The primary endpoint was significantly reduced by prasugrel in the overall NSTE-ACS population (hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.73-0.93, p=0.002) as well as in unstable angina (UA) and in non-ST elevation myocardial infarction (NSTEMI) patient subgroups (interaction p value=0.39). Although non-coronary artery bypass graft (CABG) TIMI major bleeding was increased with prasugrel as compared with clopidogrel (HR 1.40, 95% CI 1.05-1.88, p=0.02), there was a net clinical benefit in patients assigned to prasugrel (HR 0.89, 95% CI 0.80-1.00, p=0.043), which was consistent for UA and NSTEMI subgroups (interaction p value=0.84 and 0.72). In patients who met the criteria for prasugrel use recommended by the European Medicines Agency, thus excluding from the analysis patients with prior transient ischemic attack (TIA)/stroke, with weight <60 kg or age ≥75 years, and censoring follow-up at 365 days, (European Union (EU)-label cohort) prasugrel showed superiority over clopidogrel with regard to the primary endpoint (HR 0.73, 95% CI 0.63-0.85, p<0.0001) for the entire NSTE-ACS population, as well as for UA patients and NSTEMI patients without significant differences in non-CABG TIMI major bleeding.
  
  
  CONCLUSIONS
  Prasugrel, as compared with clopidogrel, significantly reduced the primary endpoint of the TRITON-TIMI 38 trial in NSTE-ACS patients, as well as in the UA and NSTEMI groups. A significant reduction in the primary endpoint without increased bleeding was observed in the EU-label cohort.
authors.affiliation: Coronary Care Unit, IRCCS Policlinico S.Matteo, Pavia, Italy s.deservi@smatteo.pv.it.
authors.forename: Stefano
authors.initials: S
authors.lastname: De Servi
authors.affiliation: Lilly Deutschland GmbH, Germany.
authors.forename: Jochen
authors.initials: J
authors.lastname: Goedicke
authors.affiliation: Daiichi Sankyo Europe GmbH, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Schirmer
authors.affiliation: Third Faculty of Medicine, Charles University Prague, Czech Republic.
authors.forename: Petr
authors.initials: P
authors.lastname: Widimsky
mesh_terms: D000789:Angina, Unstable / Q000188:drug therapy*; D000077144:Clopidogrel; D004311:Double-Blind Method; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy*; D010879:Piperazines / Q000627:therapeutic use*; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D000068799:Prasugrel Hydrochloride; D012307:Risk Factors; D013876:Thiophenes / Q000627:therapeutic use*; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D010879:Piperazines; D010975:Platelet Aggregation Inhibitors; D013876:Thiophenes; D000077144:Clopidogrel; D000068799:Prasugrel Hydrochloride; D013988:Ticlopidine
keywords: Acute coronary syndrome; clopidogrel; percutaneous coronary intervention; prasugrel