title: Early and late benefits of prasugrel in patients with acute coronary syndromes undergoing percutaneous coronary intervention: a TRITON-TIMI 38 (TRial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet InhibitioN with Prasugrel-Thrombolysis In Myocardial Infarction) analysis.
abstract: OBJECTIVE
  We evaluated the relative contributions of the loading and maintenance doses of prasugrel on events in a TRITON-TIMI 38 (TRial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet InhibitioN with Prasugrel-Thrombolysis In Myocardial Infarction) analysis.
  
  
  BACKGROUND
  Prasugrel is superior to clopidogrel in preventing ischemic events in patients with an acute coronary syndrome who are undergoing percutaneous coronary intervention, but it is associated with an increased risk of major bleeding.
  
  
  METHODS
  Landmark analyses for efficacy, safety, and net clinical benefit were performed from randomization to day 3 and from day 3 to the end of the trial.
  
  
  RESULTS
  Significant reductions in ischemic events, including myocardial infarction, stent thrombosis, and urgent target vessel revascularization, were observed with the use of prasugrel both during the first 3 days and from 3 days to the end of the trial. Thrombolysis In Myocardial Infarction major non-coronary artery bypass graft bleeding was similar to clopidogrel during the first 3 days but was significantly greater with the use of prasugrel from 3 days to the end of the study. Net clinical benefit significantly favored prasugrel both early and late in the trial.
  
  
  CONCLUSIONS
  Both the loading dose and maintenance dose of prasugrel were superior to clopidogrel for the reduction of ischemic events. This result emphasizes the importance of maintaining high levels of inhibition of platelet aggregation via P2Y(12) receptor inhibition, not only for the prevention of periprocedural ischemic events but also during long-term follow-up. The excess major bleeding observed with the use of prasugrel occurred predominantly during the maintenance phase. Approaches to reduce the relative excess of bleeding with prasugrel should focus on the maintenance dose (e.g., reduction in maintenance dose in previously reported high-risk subgroups, such as the elderly and those patients with low body weight). (A Comparison of CS-747 and Clopidogrel in Acute Coronary Syndrome Subjects Who Are to Undergo Percutaneous Coronary Intervention; NCT00097591).
authors.affiliation: Brigham and Women's Hospital, Boston, Massachusetts 02115, USA. eantman@rics.bwh.harvard.edu
authors.forename: Elliott M
authors.initials: EM
authors.lastname: Antman
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Wiviott
authors.forename: Sabina A
authors.initials: SA
authors.lastname: Murphy
authors.forename: Juri
authors.initials: J
authors.lastname: Voitk
authors.forename: Yonathan
authors.initials: Y
authors.lastname: Hasin
authors.forename: Petr
authors.initials: P
authors.lastname: Widimsky
authors.forename: Harish
authors.initials: H
authors.lastname: Chandna
authors.forename: William
authors.initials: W
authors.lastname: Macias
authors.forename: Carolyn H
authors.initials: CH
authors.lastname: McCabe
authors.forename: Eugene
authors.initials: E
authors.lastname: Braunwald
mesh_terms: D054058:Acute Coronary Syndrome / Q000188:drug therapy* / Q000628:therapy; D000789:Angina, Unstable / Q000188:drug therapy / Q000628:therapy; D015906:Angioplasty, Balloon, Coronary; D001241:Aspirin / Q000627:therapeutic use; D000077144:Clopidogrel; D003131:Combined Modality Therapy; D004359:Drug Therapy, Combination; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D053208:Kaplan-Meier Estimate; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000628:therapy; D017202:Myocardial Ischemia / Q000517:prevention & control; D010879:Piperazines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000068799:Prasugrel Hydrochloride; D016016:Proportional Hazards Models; D058919:Purinergic P2 Receptor Antagonists; D015607:Stents; D013876:Thiophenes / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use
chemical_list: D010879:Piperazines; D010975:Platelet Aggregation Inhibitors; D058919:Purinergic P2 Receptor Antagonists; D013876:Thiophenes; D000077144:Clopidogrel; D000068799:Prasugrel Hydrochloride; D013988:Ticlopidine; D001241:Aspirin