title: Long-term use of ticagrelor in patients with prior myocardial infarction.
abstract: BACKGROUND
  The potential benefit of dual antiplatelet therapy beyond 1 year after a myocardial infarction has not been established. We investigated the efficacy and safety of ticagrelor, a P2Y12 receptor antagonist with established efficacy after an acute coronary syndrome, in this context.
  
  
  METHODS
  We randomly assigned, in a double-blind 1:1:1 fashion, 21,162 patients who had had a myocardial infarction 1 to 3 years earlier to ticagrelor at a dose of 90 mg twice daily, ticagrelor at a dose of 60 mg twice daily, or placebo. All the patients were to receive low-dose aspirin and were followed for a median of 33 months. The primary efficacy end point was the composite of cardiovascular death, myocardial infarction, or stroke. The primary safety end point was Thrombolysis in Myocardial Infarction (TIMI) major bleeding.
  
  
  RESULTS
  The two ticagrelor doses each reduced, as compared with placebo, the rate of the primary efficacy end point, with Kaplan-Meier rates at 3 years of 7.85% in the group that received 90 mg of ticagrelor twice daily, 7.77% in the group that received 60 mg of ticagrelor twice daily, and 9.04% in the placebo group (hazard ratio for 90 mg of ticagrelor vs. placebo, 0.85; 95% confidence interval [CI], 0.75 to 0.96; P=0.008; hazard ratio for 60 mg of ticagrelor vs. placebo, 0.84; 95% CI, 0.74 to 0.95; P=0.004). Rates of TIMI major bleeding were higher with ticagrelor (2.60% with 90 mg and 2.30% with 60 mg) than with placebo (1.06%) (P<0.001 for each dose vs. placebo); the rates of intracranial hemorrhage or fatal bleeding in the three groups were 0.63%, 0.71%, and 0.60%, respectively.
  
  
  CONCLUSIONS
  In patients with a myocardial infarction more than 1 year previously, treatment with ticagrelor significantly reduced the risk of cardiovascular death, myocardial infarction, or stroke and increased the risk of major bleeding. (Funded by AstraZeneca; PEGASUS-TIMI 54 ClinicalTrials.gov number, NCT01225562.).
authors.affiliation: From the Thrombolysis in Myocardial Infarction (TIMI) Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston (M.P.B., D.L.B., G.M., M.P.F., K.I., S.A.M., S.D.W., E.B., M.S.S.); the Cardiovascular Division, Department of Medicine, Newark Beth Israel Medical Center, Rutgers-New Jersey Medical School, Newark (M.C.); French Alliance for Cardiovascular Trials, Département Hospitalo-Universitaire Fibrosis, Inflammation, Remodeling, Hôpital Bichat, Assistance Publique-Hôpitaux de Paris, INSERM Unité 1148, and Université Paris-Diderot, Sorbonne Paris Cité - all in Paris (P.G.S.); National Heart and Lung Institute, Royal Brompton Hospital, Imperial College, London (P.G.S.), and Department of Cardiovascular Science, University of Sheffield, Sheffield, United Kingdom (R.F.S.); AstraZeneca, Mölndal, Sweden (E.C.J., O.B., P.H.); Icahn School of Medicine at Mount Sinai, New York (S.B.); Canisius-Wilhelmina Hospital, Nijmegen, the Netherlands (T.O.O.); Postgraduate Medical School, Grochowski Hospital, Warsaw, Poland (A.B.); Montreal Heart Institute, Université de Montréal, Montreal (P.T.); Cardiology Research Center, Moscow (M.R.); Kerckhoff Heart Center, Bad Nauheim, and University of Giessen, Giessen - both in Germany (C.H.); Department of Medicine (Cardiology), Tokai University School of Medicine, Isehara, Japan (S.G.); University Hospital, Jihlavska, Brno, Czech Republic (J.S.); Heart Institute (InCor)-University of São Paulo Medical School, São Paulo (J.C.N.); and the Department of Cardiology, Military Hospital, Budapest, Hungary (R.G.K.).
authors.forename: Marc P
authors.initials: MP
authors.lastname: Bonaca
authors.forename: Deepak L
authors.initials: DL
authors.lastname: Bhatt
authors.forename: Marc
authors.initials: M
authors.lastname: Cohen
authors.forename: Philippe Gabriel
authors.initials: PG
authors.lastname: Steg
authors.forename: Robert F
authors.initials: RF
authors.lastname: Storey
authors.forename: Eva C
authors.initials: EC
authors.lastname: Jensen
authors.forename: Giulia
authors.initials: G
authors.lastname: Magnani
authors.forename: Sameer
authors.initials: S
authors.lastname: Bansilal
authors.forename: M Polly
authors.initials: MP
authors.lastname: Fish
authors.forename: Kyungah
authors.initials: K
authors.lastname: Im
authors.forename: Olof
authors.initials: O
authors.lastname: Bengtsson
authors.forename: Ton
authors.initials: T
authors.lastname: Oude Ophuis
authors.forename: Andrzej
authors.initials: A
authors.lastname: Budaj
authors.forename: Pierre
authors.initials: P
authors.lastname: Theroux
authors.forename: Mikhail
authors.initials: M
authors.lastname: Ruda
authors.forename: Christian
authors.initials: C
authors.lastname: Hamm
authors.forename: Shinya
authors.initials: S
authors.lastname: Goto
authors.forename: Jindrich
authors.initials: J
authors.lastname: Spinar
authors.forename: José Carlos
authors.initials: JC
authors.lastname: Nicolau
authors.forename: Robert G
authors.initials: RG
authors.lastname: Kiss
authors.forename: Sabina A
authors.initials: SA
authors.lastname: Murphy
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Wiviott
authors.forename: Peter
authors.initials: P
authors.lastname: Held
authors.forename: Eugene
authors.initials: E
authors.lastname: Braunwald
authors.forename: Marc S
authors.initials: MS
authors.lastname: Sabatine
mesh_terms: D000241:Adenosine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D000368:Aged; D001241:Aspirin / Q000008:administration & dosage; D002318:Cardiovascular Diseases / Q000401:mortality / Q000517:prevention & control; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D020300:Intracranial Hemorrhages / Q000139:chemically induced; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D058921:Purinergic P2Y Receptor Antagonists / Q000008:administration & dosage / Q000009:adverse effects; D012306:Risk; D055502:Secondary Prevention; D000077486:Ticagrelor
chemical_list: D010975:Platelet Aggregation Inhibitors; D058921:Purinergic P2Y Receptor Antagonists; D000077486:Ticagrelor; D000241:Adenosine; D001241:Aspirin