title: Reduction in Ischemic Events With Ticagrelor in Diabetic Patients With Prior Myocardial Infarction in PEGASUS-TIMI 54.
abstract: BACKGROUND
  Patients with diabetes appear to be at elevated risk of atherothrombotic events.
  
  
  OBJECTIVE
  The purpose of this study was to determine the effect of antiplatelet therapy with ticagrelor on recurrent ischemic events in patients with diabetes and prior myocardial infarction (MI).
  
  
  METHODS
  We examined the subgroups of patients with diabetes (n = 6,806) and without diabetes (n = 14,355) from PEGASUS-TIMI 54 (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin-Thrombolysis In Myocardial Infarction 54), in which 21,162 patients with a history of MI 1 to 3 years prior and with additional risk factors were randomized to ticagrelor (90 or 60 mg twice daily) or placebo. Patients were followed for a median of 33 months. The primary efficacy endpoint was major adverse cardiovascular events (MACE) (cardiovascular death, MI, stroke) and the primary safety endpoint was TIMI (Thrombolysis In Myocardial Infarction) major bleeding.
  
  
  RESULTS
  The relative risk reduction in MACE with ticagrelor was consistent for the pooled doses versus placebo in patients with diabetes (hazard ratio [HR]: 0.84; 95% confidence interval [CI]: 0.72 to 0.99; p = 0.035) and without diabetes (HR: 0.84; 95% CI: 0.74 to 0.96; p = 0.013; p interaction = 0.99). As patients with diabetes were at higher risk of MACE, the absolute risk reduction tended to be greater in patients with versus without diabetes (1.5% vs. 1.1%, with corresponding 3-year number needed to treat of 67 vs. 91). In patients with diabetes requiring pharmacological therapy (n = 5,960), the absolute risk reduction was 1.9% with a 3-year number needed to treat of 53. Additionally, in patients with diabetes, ticagrelor reduced cardiovascular death by 22% and coronary heart disease death by 34%. Similar to patients without diabetes, there was increased TIMI major bleeding in patients with diabetes (HR: 2.56; 95% CI: 1.52 to 4.33; p = 0.0004).
  
  
  CONCLUSIONS
  In patients with diabetes with prior MI, adding ticagrelor to aspirin significantly reduces the risk of recurrent ischemic events, including cardiovascular and coronary heart disease death. (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin [PEGASUS]; NCT01225562).
authors.affiliation: TIMI Study Group, Brigham and Women's Hospital Heart & Vascular Center, Harvard Medical School, Boston, Massachusetts. Electronic address: dlbhattmd@post.harvard.edu.
authors.forename: Deepak L
authors.initials: DL
authors.lastname: Bhatt
authors.affiliation: TIMI Study Group, Brigham and Women's Hospital Heart & Vascular Center, Harvard Medical School, Boston, Massachusetts.
authors.forename: Marc P
authors.initials: MP
authors.lastname: Bonaca
authors.affiliation: Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Sameer
authors.initials: S
authors.lastname: Bansilal
authors.affiliation: University of Florida, Jacksonville, Florida.
authors.forename: Dominick J
authors.initials: DJ
authors.lastname: Angiolillo
authors.affiliation: Cardiovascular Division, Newark Beth Israel Medical Center, Rutgers-New Jersey Medical School, Newark, New Jersey.
authors.forename: Marc
authors.initials: M
authors.lastname: Cohen
authors.affiliation: University of Sheffield, Sheffield, United Kingdom.
authors.forename: Robert F
authors.initials: RF
authors.lastname: Storey
authors.affiliation: TIMI Study Group, Brigham and Women's Hospital Heart & Vascular Center, Harvard Medical School, Boston, Massachusetts.
authors.forename: Kyungah
authors.initials: K
authors.lastname: Im
authors.affiliation: TIMI Study Group, Brigham and Women's Hospital Heart & Vascular Center, Harvard Medical School, Boston, Massachusetts.
authors.forename: Sabina A
authors.initials: SA
authors.lastname: Murphy
authors.affiliation: AstraZeneca R&D, Mölndal, Sweden.
authors.forename: Peter
authors.initials: P
authors.lastname: Held
authors.affiliation: TIMI Study Group, Brigham and Women's Hospital Heart & Vascular Center, Harvard Medical School, Boston, Massachusetts.
authors.forename: Eugene
authors.initials: E
authors.lastname: Braunwald
authors.affiliation: TIMI Study Group, Brigham and Women's Hospital Heart & Vascular Center, Harvard Medical School, Boston, Massachusetts.
authors.forename: Marc S
authors.initials: MS
authors.lastname: Sabatine
authors.affiliation: Département Hospitalo-Universitaire-Fibrosis, Inflammation, REmodelling, Hôpital Bichat, Assistance Publique-Hôpitaux de Paris, Université Paris-Diderot, Sorbonne-Paris Cité, and the French Alliance for Cardiovascular Clinical Trials, an F-CRIN network, INSERM U-1148, Paris, France.
authors.forename: Ph Gabriel
authors.initials: PG
authors.lastname: Steg
mesh_terms: D000241:Adenosine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D000368:Aged; D003327:Coronary Disease / Q000401:mortality; D003920:Diabetes Mellitus / Q000453:epidemiology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced / Q000453:epidemiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology / Q000517:prevention & control; D058921:Purinergic P2Y Receptor Antagonists / Q000008:administration & dosage / Q000009:adverse effects*; D055502:Secondary Prevention; D020521:Stroke / Q000453:epidemiology / Q000517:prevention & control; D000077486:Ticagrelor
chemical_list: D058921:Purinergic P2Y Receptor Antagonists; D000077486:Ticagrelor; D000241:Adenosine
keywords: acute coronary syndrome; dual antiplatelet therapy; myocardial infarction; platelets