title: Ticagrelor for Prevention of Ischemic Events After Myocardial Infarction in Patients With Peripheral Artery Disease.
abstract: BACKGROUND
  Peripheral artery disease (PAD) is associated with heightened ischemic and bleeding risk in patients with prior myocardial infarction (MI).
  
  
  OBJECTIVE
  This study evaluated the efficacy and safety of ticagrelor on major cardiovascular (CV) events and major adverse limb events in patients with PAD and a prior MI.
  
  
  METHODS
  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) randomized 21,162 patients with prior MI (1 to 3 years) to ticagrelor 90 mg twice daily, ticagrelor 60 mg twice daily, or placebo, all on a background of low-dose aspirin. History of PAD was obtained at baseline. Occurrences of major adverse cardiovascular events (MACE) (defined as CV death, MI, or stroke) and major adverse limb events (MALE) (defined as acute limb ischemia or peripheral revascularization for ischemia) were recorded in follow-up.
  
  
  RESULTS
  A total of 1,143 patients (5%) had known PAD. In the placebo arm, those with PAD (n = 404) had higher rates of MACE at 3 years than those without (n = 6,663; 19.3% vs. 8.4%; p < 0.001), which persisted after adjusting for baseline differences (adjusted hazard ratio: 1.60; 95% confidence interval: 1.20 to 2.13; p = 0.0013), and higher rates of acute limb ischemia (1.0% vs. 0.1%) and peripheral revascularization procedures (9.15% vs. 0.46%). Whereas the relative risk reduction in MACE with ticagrelor was consistent, regardless of PAD, patients with PAD had a greater absolute risk reduction of 4.1% (number needed to treat: 25) due to their higher absolute risk. The absolute excess of TIMI major bleeding was 0.12% (number needed to harm: 834). The 60-mg dose had particularly favorable outcomes for CV and all-cause mortality. Ticagrelor (pooled doses) reduced the risk of MALE (hazard ratio: 0.65; 95% confidence interval: 0.44 to 0.95; p = 0.026).
  
  
  CONCLUSIONS
  Among stable patients with prior MI, those with concomitant PAD have heightened ischemic risk. In these patients, ticagrelor reduced MACE, with a large absolute risk reduction, and MALE. (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin [PEGASUS-TIMI 54]; NCT01225562).
authors.affiliation: TIMI Study Group, Brigham and Women's Hospital Heart & Vascular Center, Boston, Massachusetts. Electronic address: mbonaca@partners.org.
authors.forename: Marc P
authors.initials: MP
authors.lastname: Bonaca
authors.affiliation: TIMI Study Group, Brigham and Women's Hospital Heart & Vascular Center, Boston, Massachusetts.
authors.forename: Deepak L
authors.initials: DL
authors.lastname: Bhatt
authors.affiliation: Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, United Kingdom.
authors.forename: Robert F
authors.initials: RF
authors.lastname: Storey
authors.affiliation: French Alliance for Cardiovascular Trials, Université Paris-Diderot, Paris, France.
authors.forename: Ph Gabriel
authors.initials: PG
authors.lastname: Steg
authors.affiliation: Cardiovascular Division, Newark Beth Israel Medical Center, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Marc
authors.initials: M
authors.lastname: Cohen
authors.affiliation: TIMI Study Group, Brigham and Women's Hospital Heart & Vascular Center, Boston, Massachusetts.
authors.forename: Julia
authors.initials: J
authors.lastname: Kuder
authors.affiliation: TIMI Study Group, Brigham and Women's Hospital Heart & Vascular Center, Boston, Massachusetts.
authors.forename: Erica
authors.initials: E
authors.lastname: Goodrich
authors.affiliation: Heart Institute (InCor)-University of São Paulo Medical School, São Paulo, Brazil.
authors.forename: José C
authors.initials: JC
authors.lastname: Nicolau
authors.affiliation: Ukranian Strazhesko Institute of Cardiology, Kiev, Ukraine.
authors.forename: Alexander
authors.initials: A
authors.lastname: Parkhomenko
authors.affiliation: Hospital Universitario La Paz, Instituto de Investigación La Paz, Madrid, Spain.
authors.forename: José
authors.initials: J
authors.lastname: López-Sendón
authors.affiliation: Department of Molecular and Clinical Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Mikael
authors.initials: M
authors.lastname: Dellborg
authors.affiliation: Life Fourways Hospital, Randburg, South Africa.
authors.forename: Anthony
authors.initials: A
authors.lastname: Dalby
authors.affiliation: University Hospital, Jihlavska, Brno, Czech Republic.
authors.forename: Jindřich
authors.initials: J
authors.lastname: Špinar
authors.affiliation: Division of Medicine, Cardiac & Critical Care Services, Flinders Medical Centre, South Australia, Australia.
authors.forename: Philip
authors.initials: P
authors.lastname: Aylward
authors.affiliation: Cardiovascular Division, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Ramón
authors.initials: R
authors.lastname: Corbalán
authors.affiliation: Philippine Heart Center, University of the Philippines College of Medicine, Manila, Philippines.
authors.forename: Maria Teresa B
authors.initials: MTB
authors.lastname: Abola
authors.affiliation: AstraZeneca R&D, Mölndal, Sweden.
authors.forename: Eva C
authors.initials: EC
authors.lastname: Jensen
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, Boston, Massachusetts.
authors.forename: Eugene
authors.initials: E
authors.lastname: Braunwald
authors.affiliation: TIMI Study Group, Brigham and Women's Hospital Heart & Vascular Center, Boston, Massachusetts.
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; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced / Q000453:epidemiology; D006801:Humans; D007511:Ischemia / Q000453:epidemiology / Q000517:prevention & control / Q000601:surgery; D035002:Lower Extremity / Q000098:blood supply / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology* / Q000517:prevention & control; D058729:Peripheral Arterial Disease / Q000453:epidemiology*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage; D058921:Purinergic P2Y Receptor Antagonists / Q000008:administration & dosage* / Q000009:adverse effects; D055502:Secondary Prevention; D020521:Stroke / Q000453:epidemiology / Q000517:prevention & control; D000077486:Ticagrelor; D058017:Vascular Grafting / Q000706:statistics & numerical data
chemical_list: D010975:Platelet Aggregation Inhibitors; D058921:Purinergic P2Y Receptor Antagonists; D000077486:Ticagrelor; D000241:Adenosine; D001241:Aspirin
keywords: acute limb ischemia; major adverse cardiovascular events; major adverse limb events; peripheral arterial disease; ticagrelor