title: Pretreatment with prasugrel in non-ST-segment elevation acute coronary syndromes.
abstract: BACKGROUND
  Although P2Y12 antagonists are effective in patients with non-ST-segment elevation (NSTE) acute coronary syndromes, the effect of the timing of administration--before or after coronary angiography--is not known. We evaluated the effect of administering the P2Y12 antagonist prasugrel at the time of diagnosis versus administering it after the coronary angiography if percutaneous coronary intervention (PCI) was indicated.
  
  
  METHODS
  We enrolled 4033 patients with NSTE acute coronary syndromes and a positive troponin level who were scheduled to undergo coronary angiography within 2 to 48 hours after randomization. Patients were randomly assigned to receive prasugrel (a 30-mg loading dose) before the angiography (pretreatment group) or placebo (control group). When PCI was indicated, an additional 30 mg of prasugrel was given in the pretreatment group at the time of PCI and 60 mg of prasugrel was given in the control group.
  
  
  RESULTS
  The rate of the primary efficacy end point, a composite of death from cardiovascular causes, myocardial infarction, stroke, urgent revascularization, or glycoprotein IIb/IIIa inhibitor rescue therapy (glycoprotein IIb/IIIa bailout) through day 7, did not differ significantly between the two groups (hazard ratio with pretreatment, 1.02; 95% confidence interval [CI], 0.84 to 1.25; P=0.81). The rate of the key safety end point of all Thrombolysis in Myocardial Infarction (TIMI) major bleeding episodes, whether related or not related to coronary-artery bypass grafting (CABG), through day 7 was increased with pretreatment (hazard ratio, 1.90; 95% CI, 1.19 to 3.02; P=0.006). The rates of TIMI major bleeding and life-threatening bleeding not related to CABG were increased by a factor of 3 and 6, respectively. Pretreatment did not reduce the rate of the primary outcome among patients undergoing PCI (69% of the patients) but increased the rate of TIMI major bleeding at 7 days. All the results were confirmed at 30 days and in prespecified subgroups.
  
  
  CONCLUSIONS
  Among patients with NSTE acute coronary syndromes who were scheduled to undergo catheterization, pretreatment with prasugrel did not reduce the rate of major ischemic events up to 30 days but increased the rate of major bleeding complications. (Funded by Daiichi Sankyo and Eli Lilly; ACCOAST ClinicalTrials.gov number, NCT01015287.).
authors.affiliation: Institut de Cardiologie, Centre Hospitalier Universitaire Pitié–Salpêtrière (ACTION group, Assistance Publique–Hôpitaux de Paris [AP-HP], Université Paris 6), Paris, France. gilles.montalescot@psl.aphp.fr
authors.forename: Gilles
authors.initials: G
authors.lastname: Montalescot
authors.forename: Leonardo
authors.initials: L
authors.lastname: Bolognese
authors.forename: Dariusz
authors.initials: D
authors.lastname: Dudek
authors.forename: Patrick
authors.initials: P
authors.lastname: Goldstein
authors.forename: Christian
authors.initials: C
authors.lastname: Hamm
authors.forename: Jean-Francois
authors.initials: JF
authors.lastname: Tanguay
authors.forename: Jurrien M
authors.initials: JM
authors.lastname: ten Berg
authors.forename: Debra L
authors.initials: DL
authors.lastname: Miller
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Costigan
authors.forename: Jochen
authors.initials: J
authors.lastname: Goedicke
authors.forename: Johanne
authors.initials: J
authors.lastname: Silvain
authors.forename: Paolo
authors.initials: P
authors.lastname: Angioli
authors.forename: Jacek
authors.initials: J
authors.lastname: Legutko
authors.forename: Margit
authors.initials: M
authors.lastname: Niethammer
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Motovska
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Jakubowski
authors.forename: Guillaume
authors.initials: G
authors.lastname: Cayla
authors.forename: Luigi Oltrona
authors.initials: LO
authors.lastname: Visconti
authors.forename: Eric
authors.initials: E
authors.lastname: Vicaut
authors.forename: Petr
authors.initials: P
authors.lastname: Widimsky
mesh_terms: D054058:Acute Coronary Syndrome / Q000188:drug therapy* / Q000628:therapy; D000368:Aged; D017023:Coronary Angiography; D001026:Coronary Artery Bypass; D004311:Double-Blind Method; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy; D062645:Percutaneous Coronary Intervention; D010879:Piperazines / Q000008:administration & dosage* / Q000009:adverse effects; D000068799:Prasugrel Hydrochloride; D011292:Premedication; D058921:Purinergic P2Y Receptor Antagonists / Q000008:administration & dosage* / Q000009:adverse effects; D013876:Thiophenes / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D010879:Piperazines; D058921:Purinergic P2Y Receptor Antagonists; D013876:Thiophenes; D000068799:Prasugrel Hydrochloride