title: Ticagrelor versus Clopidogrel in Symptomatic Peripheral Artery Disease.
abstract: Peripheral artery disease is considered to be a manifestation of systemic atherosclerosis with associated adverse cardiovascular and limb events. Data from previous trials have suggested that patients receiving clopidogrel monotherapy had a lower risk of cardiovascular events than those receiving aspirin. We wanted to compare clopidogrel with ticagrelor, a potent antiplatelet agent, in patients with peripheral artery disease.
  
  
  
  In this double-blind, event-driven trial, we randomly assigned 13,885 patients with symptomatic peripheral artery disease to receive monotherapy with ticagrelor (90 mg twice daily) or clopidogrel (75 mg once daily). Patients were eligible if they had an ankle-brachial index (ABI) of 0.80 or less or had undergone previous revascularization of the lower limbs. The primary efficacy end point was a composite of adjudicated cardiovascular death, myocardial infarction, or ischemic stroke. The primary safety end point was major bleeding. The median follow-up was 30 months.
  
  
  
  The median age of the patients was 66 years, and 72% were men; 43% were enrolled on the basis of the ABI and 57% on the basis of previous revascularization. The mean baseline ABI in all patients was 0.71, 76.6% of the patients had claudication, and 4.6% had critical limb ischemia. The primary efficacy end point occurred in 751 of 6930 patients (10.8%) receiving ticagrelor and in 740 of 6955 (10.6%) receiving clopidogrel (hazard ratio, 1.02; 95% confidence interval [CI], 0.92 to 1.13; P=0.65). In each group, acute limb ischemia occurred in 1.7% of the patients (hazard ratio, 1.03; 95% CI, 0.79 to 1.33; P=0.85) and major bleeding in 1.6% (hazard ratio, 1.10; 95% CI, 0.84 to 1.43; P=0.49).
  
  
  
  In patients with symptomatic peripheral artery disease, ticagrelor was not shown to be superior to clopidogrel for the reduction of cardiovascular events. Major bleeding occurred at similar rates among the patients in the two trial groups. (Funded by AstraZeneca; EUCLID ClinicalTrials.gov number, NCT01732822 .).
authors.affiliation: From the University of Colorado School of Medicine and CPC Clinical Research, Aurora (W.R.H.); Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh (F.G.R.F.); Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC (G.H., W.S.J., C.R., M.R.P.); the Departments of Medicine and Surgery, New York University School of Medicine, New York (J.S.B.); Swiss Cardiovascular Center, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland (I.B.); AstraZeneca Gothenburg, Mölndal (P.H., J.B., M.M.), and Faculty of Medicine and Health, Örebro University, Örebro (L.N.) - both in Sweden; AstraZeneca Gaithersburg, Gaithersburg, MD (B.G.K.); and Stanford Center for Clinical Research, Stanford University School of Medicine, Stanford, CA (K.W.M.).
authors.forename: William R
authors.initials: WR
authors.lastname: Hiatt
authors.affiliation: From the University of Colorado School of Medicine and CPC Clinical Research, Aurora (W.R.H.); Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh (F.G.R.F.); Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC (G.H., W.S.J., C.R., M.R.P.); the Departments of Medicine and Surgery, New York University School of Medicine, New York (J.S.B.); Swiss Cardiovascular Center, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland (I.B.); AstraZeneca Gothenburg, Mölndal (P.H., J.B., M.M.), and Faculty of Medicine and Health, Örebro University, Örebro (L.N.) - both in Sweden; AstraZeneca Gaithersburg, Gaithersburg, MD (B.G.K.); and Stanford Center for Clinical Research, Stanford University School of Medicine, Stanford, CA (K.W.M.).
authors.forename: F Gerry R
authors.initials: FG
authors.lastname: Fowkes
authors.affiliation: From the University of Colorado School of Medicine and CPC Clinical Research, Aurora (W.R.H.); Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh (F.G.R.F.); Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC (G.H., W.S.J., C.R., M.R.P.); the Departments of Medicine and Surgery, New York University School of Medicine, New York (J.S.B.); Swiss Cardiovascular Center, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland (I.B.); AstraZeneca Gothenburg, Mölndal (P.H., J.B., M.M.), and Faculty of Medicine and Health, Örebro University, Örebro (L.N.) - both in Sweden; AstraZeneca Gaithersburg, Gaithersburg, MD (B.G.K.); and Stanford Center for Clinical Research, Stanford University School of Medicine, Stanford, CA (K.W.M.).
authors.forename: Gretchen
authors.initials: G
authors.lastname: Heizer
authors.affiliation: From the University of Colorado School of Medicine and CPC Clinical Research, Aurora (W.R.H.); Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh (F.G.R.F.); Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC (G.H., W.S.J., C.R., M.R.P.); the Departments of Medicine and Surgery, New York University School of Medicine, New York (J.S.B.); Swiss Cardiovascular Center, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland (I.B.); AstraZeneca Gothenburg, Mölndal (P.H., J.B., M.M.), and Faculty of Medicine and Health, Örebro University, Örebro (L.N.) - both in Sweden; AstraZeneca Gaithersburg, Gaithersburg, MD (B.G.K.); and Stanford Center for Clinical Research, Stanford University School of Medicine, Stanford, CA (K.W.M.).
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Berger
authors.affiliation: From the University of Colorado School of Medicine and CPC Clinical Research, Aurora (W.R.H.); Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh (F.G.R.F.); Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC (G.H., W.S.J., C.R., M.R.P.); the Departments of Medicine and Surgery, New York University School of Medicine, New York (J.S.B.); Swiss Cardiovascular Center, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland (I.B.); AstraZeneca Gothenburg, Mölndal (P.H., J.B., M.M.), and Faculty of Medicine and Health, Örebro University, Örebro (L.N.) - both in Sweden; AstraZeneca Gaithersburg, Gaithersburg, MD (B.G.K.); and Stanford Center for Clinical Research, Stanford University School of Medicine, Stanford, CA (K.W.M.).
authors.forename: Iris
authors.initials: I
authors.lastname: Baumgartner
authors.affiliation: From the University of Colorado School of Medicine and CPC Clinical Research, Aurora (W.R.H.); Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh (F.G.R.F.); Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC (G.H., W.S.J., C.R., M.R.P.); the Departments of Medicine and Surgery, New York University School of Medicine, New York (J.S.B.); Swiss Cardiovascular Center, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland (I.B.); AstraZeneca Gothenburg, Mölndal (P.H., J.B., M.M.), and Faculty of Medicine and Health, Örebro University, Örebro (L.N.) - both in Sweden; AstraZeneca Gaithersburg, Gaithersburg, MD (B.G.K.); and Stanford Center for Clinical Research, Stanford University School of Medicine, Stanford, CA (K.W.M.).
authors.forename: Peter
authors.initials: P
authors.lastname: Held
authors.affiliation: From the University of Colorado School of Medicine and CPC Clinical Research, Aurora (W.R.H.); Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh (F.G.R.F.); Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC (G.H., W.S.J., C.R., M.R.P.); the Departments of Medicine and Surgery, New York University School of Medicine, New York (J.S.B.); Swiss Cardiovascular Center, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland (I.B.); AstraZeneca Gothenburg, Mölndal (P.H., J.B., M.M.), and Faculty of Medicine and Health, Örebro University, Örebro (L.N.) - both in Sweden; AstraZeneca Gaithersburg, Gaithersburg, MD (B.G.K.); and Stanford Center for Clinical Research, Stanford University School of Medicine, Stanford, CA (K.W.M.).
authors.forename: Brian G
authors.initials: BG
authors.lastname: Katona
authors.affiliation: From the University of Colorado School of Medicine and CPC Clinical Research, Aurora (W.R.H.); Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh (F.G.R.F.); Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC (G.H., W.S.J., C.R., M.R.P.); the Departments of Medicine and Surgery, New York University School of Medicine, New York (J.S.B.); Swiss Cardiovascular Center, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland (I.B.); AstraZeneca Gothenburg, Mölndal (P.H., J.B., M.M.), and Faculty of Medicine and Health, Örebro University, Örebro (L.N.) - both in Sweden; AstraZeneca Gaithersburg, Gaithersburg, MD (B.G.K.); and Stanford Center for Clinical Research, Stanford University School of Medicine, Stanford, CA (K.W.M.).
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Mahaffey
authors.affiliation: From the University of Colorado School of Medicine and CPC Clinical Research, Aurora (W.R.H.); Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh (F.G.R.F.); Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC (G.H., W.S.J., C.R., M.R.P.); the Departments of Medicine and Surgery, New York University School of Medicine, New York (J.S.B.); Swiss Cardiovascular Center, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland (I.B.); AstraZeneca Gothenburg, Mölndal (P.H., J.B., M.M.), and Faculty of Medicine and Health, Örebro University, Örebro (L.N.) - both in Sweden; AstraZeneca Gaithersburg, Gaithersburg, MD (B.G.K.); and Stanford Center for Clinical Research, Stanford University School of Medicine, Stanford, CA (K.W.M.).
authors.forename: Lars
authors.initials: L
authors.lastname: Norgren
authors.affiliation: From the University of Colorado School of Medicine and CPC Clinical Research, Aurora (W.R.H.); Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh (F.G.R.F.); Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC (G.H., W.S.J., C.R., M.R.P.); the Departments of Medicine and Surgery, New York University School of Medicine, New York (J.S.B.); Swiss Cardiovascular Center, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland (I.B.); AstraZeneca Gothenburg, Mölndal (P.H., J.B., M.M.), and Faculty of Medicine and Health, Örebro University, Örebro (L.N.) - both in Sweden; AstraZeneca Gaithersburg, Gaithersburg, MD (B.G.K.); and Stanford Center for Clinical Research, Stanford University School of Medicine, Stanford, CA (K.W.M.).
authors.forename: W Schuyler
authors.initials: WS
authors.lastname: Jones
authors.affiliation: From the University of Colorado School of Medicine and CPC Clinical Research, Aurora (W.R.H.); Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh (F.G.R.F.); Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC (G.H., W.S.J., C.R., M.R.P.); the Departments of Medicine and Surgery, New York University School of Medicine, New York (J.S.B.); Swiss Cardiovascular Center, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland (I.B.); AstraZeneca Gothenburg, Mölndal (P.H., J.B., M.M.), and Faculty of Medicine and Health, Örebro University, Örebro (L.N.) - both in Sweden; AstraZeneca Gaithersburg, Gaithersburg, MD (B.G.K.); and Stanford Center for Clinical Research, Stanford University School of Medicine, Stanford, CA (K.W.M.).
authors.forename: Juuso
authors.initials: J
authors.lastname: Blomster
authors.affiliation: From the University of Colorado School of Medicine and CPC Clinical Research, Aurora (W.R.H.); Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh (F.G.R.F.); Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC (G.H., W.S.J., C.R., M.R.P.); the Departments of Medicine and Surgery, New York University School of Medicine, New York (J.S.B.); Swiss Cardiovascular Center, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland (I.B.); AstraZeneca Gothenburg, Mölndal (P.H., J.B., M.M.), and Faculty of Medicine and Health, Örebro University, Örebro (L.N.) - both in Sweden; AstraZeneca Gaithersburg, Gaithersburg, MD (B.G.K.); and Stanford Center for Clinical Research, Stanford University School of Medicine, Stanford, CA (K.W.M.).
authors.forename: Marcus
authors.initials: M
authors.lastname: Millegård
authors.affiliation: From the University of Colorado School of Medicine and CPC Clinical Research, Aurora (W.R.H.); Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh (F.G.R.F.); Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC (G.H., W.S.J., C.R., M.R.P.); the Departments of Medicine and Surgery, New York University School of Medicine, New York (J.S.B.); Swiss Cardiovascular Center, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland (I.B.); AstraZeneca Gothenburg, Mölndal (P.H., J.B., M.M.), and Faculty of Medicine and Health, Örebro University, Örebro (L.N.) - both in Sweden; AstraZeneca Gaithersburg, Gaithersburg, MD (B.G.K.); and Stanford Center for Clinical Research, Stanford University School of Medicine, Stanford, CA (K.W.M.).
authors.forename: Craig
authors.initials: C
authors.lastname: Reist
authors.affiliation: From the University of Colorado School of Medicine and CPC Clinical Research, Aurora (W.R.H.); Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh (F.G.R.F.); Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC (G.H., W.S.J., C.R., M.R.P.); the Departments of Medicine and Surgery, New York University School of Medicine, New York (J.S.B.); Swiss Cardiovascular Center, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland (I.B.); AstraZeneca Gothenburg, Mölndal (P.H., J.B., M.M.), and Faculty of Medicine and Health, Örebro University, Örebro (L.N.) - both in Sweden; AstraZeneca Gaithersburg, Gaithersburg, MD (B.G.K.); and Stanford Center for Clinical Research, Stanford University School of Medicine, Stanford, CA (K.W.M.).
authors.forename: Manesh R
authors.initials: MR
authors.lastname: Patel
mesh_terms: D000241:Adenosine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000368:Aged; D002318:Cardiovascular Diseases / Q000401:mortality / Q000517:prevention & control*; D000077144:Clopidogrel; D004311:Double-Blind Method; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D007383:Intermittent Claudication / Q000188:drug therapy; D007511:Ischemia / Q000188:drug therapy; D053208:Kaplan-Meier Estimate; D007866:Leg / Q000098:blood supply*; D008297:Male; D008875:Middle Aged; D058729:Peripheral Arterial Disease / Q000188:drug therapy*; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D058921:Purinergic P2Y Receptor Antagonists / Q000627:therapeutic use; D000077486:Ticagrelor; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D010975:Platelet Aggregation Inhibitors; D058921:Purinergic P2Y Receptor Antagonists; D000077144:Clopidogrel; D000077486:Ticagrelor; D000241:Adenosine; D013988:Ticlopidine