title: Design and rationale for the Effects of Ticagrelor and Clopidogrel in Patients with Peripheral Artery Disease (EUCLID) trial.
abstract: BACKGROUND
  Despite overwhelming data demonstrating the efficacy of antiplatelet therapy in heart disease and stroke, data in peripheral artery disease (PAD) are less compelling. Aspirin has modest evidence supporting a reduction in cardiovascular events in patients with PAD, whereas clopidogrel monotherapy may be more effective in PAD. Ticagrelor, a potent, reversibly binding P2Y12 receptor antagonist, is beneficial in patients with acute coronary syndrome and prior myocardial infarction. The EUCLID trial is designed to address the need for effective antiplatelet therapy in PAD to decrease the risk of cardiovascular events.
  
  
  METHODS
  EUCLID is a randomized, double-blind, parallel-group, multinational clinical trial designed to evaluate the efficacy and safety of ticagrelor compared with clopidogrel for the prevention of major adverse cardiovascular events in subjects with symptomatic PAD. Subjects with established PAD will be randomized in a 1:1 fashion to ticagrelor 90 mg twice daily or clopidogrel 75 mg daily. The primary end point is a composite of cardiovascular death, myocardial infarction, or ischemic stroke. Other end points address limb events including acute leg ischemia, need for revascularization, disease progression by ankle-brachial index, and quality of life. The primary safety objective is Thrombolysis in Myocardial Infarction-defined major bleeding. Recruitment began in December 2012 and was completed in March 2014; 13,887 patients were randomized. The trial will continue until at least 1,364 adjudicated primary end points occur.
  
  
  CONCLUSIONS
  The EUCLID study is investigating whether treatment with ticagrelor versus clopidogrel, given as antiplatelet monotherapy, will reduce the incidence of cardiovascular and limb-specific events in patients with symptomatic PAD.
authors.affiliation: Divisions of Cardiology and Vascular Surgery, Departments of Medicine and Surgery, New York University School of Medicine, New York, NY. Electronic address: Jeffrey.Berger@nyumc.org.
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Berger
authors.affiliation: Global Medicines Development, AstraZeneca, Gaithersburg, MD.
authors.forename: Brian G
authors.initials: BG
authors.lastname: Katona
authors.affiliation: Division of Cardiology, Department of Medicine, Duke University School of Medicine, Durham, NC; Duke Clinical Research Institute, Durham, NC.
authors.forename: W Schuyler
authors.initials: WS
authors.lastname: Jones
authors.affiliation: Division of Cardiology, Department of Medicine, Duke University School of Medicine, Durham, NC; Duke Clinical Research Institute, Durham, NC.
authors.forename: Manesh R
authors.initials: MR
authors.lastname: Patel
authors.affiliation: Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Norgren
authors.affiliation: Swiss Cardiovascular Centre, Division of Angiology, Bern University Hospital, INSELSPITAL, Bern, Switzerland.
authors.forename: Iris
authors.initials: I
authors.lastname: Baumgartner
authors.affiliation: AstraZeneca Research and Development, Mölndal, Sweden; Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden; University of Turku, Turku, Finland.
authors.forename: Juuso
authors.initials: J
authors.lastname: Blomster
authors.affiliation: Department of Medicine, Stanford Center for Clinical Research, Stanford University, Stanford, CA.
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Mahaffey
authors.affiliation: AstraZeneca Research and Development, Mölndal, Sweden.
authors.forename: Peter
authors.initials: P
authors.lastname: Held
authors.affiliation: AstraZeneca Research and Development, Mölndal, Sweden.
authors.forename: Marcus
authors.initials: M
authors.lastname: Millegård
authors.affiliation: Duke Clinical Research Institute, Durham, NC.
authors.forename: Gretchen
authors.initials: G
authors.lastname: Heizer
authors.affiliation: Duke Clinical Research Institute, Durham, NC.
authors.forename: Craig
authors.initials: C
authors.lastname: Reist
authors.affiliation: Centre for Population Health Sciences, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: F Gerry
authors.initials: FG
authors.lastname: Fowkes
authors.affiliation: Division of Cardiology, University of Colorado School of Medicine and CPC Clinical Research, Aurora, CO.
authors.forename: William R
authors.initials: WR
authors.lastname: Hiatt
mesh_terms: D000241:Adenosine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D000368:Aged; D055109:Ankle Brachial Index; D000077144:Clopidogrel; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000209:etiology / Q000517:prevention & control; D058729:Peripheral Arterial Disease / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D020521:Stroke / Q000209:etiology / Q000517:prevention & control; D000077486:Ticagrelor; D013988:Ticlopidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D016896:Treatment Outcome
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D000077486:Ticagrelor; D000241:Adenosine; D013988:Ticlopidine