title: Ticagrelor Compared With Clopidogrel in Patients With Prior Lower Extremity Revascularization for Peripheral Artery Disease.
abstract: BACKGROUND
  In patients with symptomatic peripheral artery disease with a history of limb revascularization, the optimal antithrombotic regimen for long-term management is unknown.
  
  
  METHODS
  The EUCLID trial (Examining Use of Ticagrelor In PAD) randomized 13 885 patients with peripheral artery disease to treatment with ticagrelor 90 mg twice daily or clopidogrel 75 mg daily. Patients were enrolled based on an abnormal ankle-brachial index ≤0.80 or a previous lower extremity revascularization. This analysis focuses on the 7875 (57%) patients enrolled based on the previous lower extremity revascularization criterion. Patients could not be enrolled within 30 days of most recent revascularization, and patients with an indication for dual antiplatelet therapy were excluded. The primary efficacy end point was a composite of cardiovascular death, myocardial infarction, or ischemic stroke. The primary safety end point was major bleeding.
  
  
  RESULTS
  Patients with a previous revascularization had a mean age of 66 years, 73% were male, and the median baseline ankle-brachial index was 0.78. After adjustment for baseline characteristics, patients enrolled based on previous revascularization had similar rates of the primary composite end point (hazard ratio [HR] 1.10, 95% confidence interval [CI] 0.98-1.23, P=0.12) and statistically significantly higher rates of myocardial infarction (HR 1.29, 95% CI 1.08-1.55, P=0.005) and acute limb ischemia (HR 4.23, 95% CI 2.86-6.25, P<0.001) when compared with patients enrolled based on ankle-brachial index criteria. No differences in ticagrelor- versus clopidogrel-treated patients were found for the primary efficacy end point (11.4% vs 11.3%; HR 1.01, 95% CI 0.88-1.15; P=0.90), all-cause mortality (9.2% vs 9.2%; HR 0.99, 95% CI 0.86-1.15; P=0.93), acute limb ischemia (2.5% vs 2.5%; HR 1.03, 95% CI 0.78-1.36; P=0.84), or major bleeding (1.9% vs 1.8%; HR 1.15, 95% CI 0.83-1.59; P=0.41). The median duration of follow-up was ≈30 months.
  
  
  CONCLUSIONS
  After adjustment for baseline characteristics, patients enrolled based on previous revascularization for peripheral artery disease had higher rates of myocardial infarction and acute limb ischemia, with similar composite rates of cardiovascular death, myocardial infarction, and stroke when compared with patients enrolled based on the ankle-brachial index criterion. No significant differences were found between ticagrelor and clopidogrel for reduction of cardiovascular or acute limb events.
  
  
  BACKGROUND
  URL: http://www.clinicaltrials.gov. Unique identifier: NCT01732822.
authors.affiliation: From Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC (W.S.J., G.H., C.R., M.P.P.); Swiss Cardiovascular Centre, Inselspital, Bern University Hospital, University of Bern, Switzerland (I.B.); University of Colorado School of Medicine and CPC Clinical Research, Aurora (W.R.H.); Department of Surgery, University of California San Francisco (M.S.C.); Department of Cardiology, Ochsner Clinical School, University of Queensland, Australia (C.J.W.); Ochsner Medical Center, New Orleans, LA (C.J.W.); Departments of Medicine and Surgery, New York University School of Medicine (J.S.B.); AstraZeneca Gothenburg, Mölndal, Sweden (P.H., J.B., M.M.); AstraZeneca Gaithersburg, MD (B.G.K.); Stanford Center for Clinical Research, Stanford University School of Medicine, CA (K.W.M.); Faculty of Medicine and Health, Örebro University, Sweden (L.N.); and Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, UK (F.G.R.F.).
authors.forename: W Schuyler
authors.initials: WS
authors.lastname: Jones
authors.affiliation: From Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC (W.S.J., G.H., C.R., M.P.P.); Swiss Cardiovascular Centre, Inselspital, Bern University Hospital, University of Bern, Switzerland (I.B.); University of Colorado School of Medicine and CPC Clinical Research, Aurora (W.R.H.); Department of Surgery, University of California San Francisco (M.S.C.); Department of Cardiology, Ochsner Clinical School, University of Queensland, Australia (C.J.W.); Ochsner Medical Center, New Orleans, LA (C.J.W.); Departments of Medicine and Surgery, New York University School of Medicine (J.S.B.); AstraZeneca Gothenburg, Mölndal, Sweden (P.H., J.B., M.M.); AstraZeneca Gaithersburg, MD (B.G.K.); Stanford Center for Clinical Research, Stanford University School of Medicine, CA (K.W.M.); Faculty of Medicine and Health, Örebro University, Sweden (L.N.); and Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, UK (F.G.R.F.).
authors.forename: Iris
authors.initials: I
authors.lastname: Baumgartner
authors.affiliation: From Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC (W.S.J., G.H., C.R., M.P.P.); Swiss Cardiovascular Centre, Inselspital, Bern University Hospital, University of Bern, Switzerland (I.B.); University of Colorado School of Medicine and CPC Clinical Research, Aurora (W.R.H.); Department of Surgery, University of California San Francisco (M.S.C.); Department of Cardiology, Ochsner Clinical School, University of Queensland, Australia (C.J.W.); Ochsner Medical Center, New Orleans, LA (C.J.W.); Departments of Medicine and Surgery, New York University School of Medicine (J.S.B.); AstraZeneca Gothenburg, Mölndal, Sweden (P.H., J.B., M.M.); AstraZeneca Gaithersburg, MD (B.G.K.); Stanford Center for Clinical Research, Stanford University School of Medicine, CA (K.W.M.); Faculty of Medicine and Health, Örebro University, Sweden (L.N.); and Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, UK (F.G.R.F.).
authors.forename: William R
authors.initials: WR
authors.lastname: Hiatt
authors.affiliation: From Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC (W.S.J., G.H., C.R., M.P.P.); Swiss Cardiovascular Centre, Inselspital, Bern University Hospital, University of Bern, Switzerland (I.B.); University of Colorado School of Medicine and CPC Clinical Research, Aurora (W.R.H.); Department of Surgery, University of California San Francisco (M.S.C.); Department of Cardiology, Ochsner Clinical School, University of Queensland, Australia (C.J.W.); Ochsner Medical Center, New Orleans, LA (C.J.W.); Departments of Medicine and Surgery, New York University School of Medicine (J.S.B.); AstraZeneca Gothenburg, Mölndal, Sweden (P.H., J.B., M.M.); AstraZeneca Gaithersburg, MD (B.G.K.); Stanford Center for Clinical Research, Stanford University School of Medicine, CA (K.W.M.); Faculty of Medicine and Health, Örebro University, Sweden (L.N.); and Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, UK (F.G.R.F.).
authors.forename: Gretchen
authors.initials: G
authors.lastname: Heizer
authors.affiliation: From Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC (W.S.J., G.H., C.R., M.P.P.); Swiss Cardiovascular Centre, Inselspital, Bern University Hospital, University of Bern, Switzerland (I.B.); University of Colorado School of Medicine and CPC Clinical Research, Aurora (W.R.H.); Department of Surgery, University of California San Francisco (M.S.C.); Department of Cardiology, Ochsner Clinical School, University of Queensland, Australia (C.J.W.); Ochsner Medical Center, New Orleans, LA (C.J.W.); Departments of Medicine and Surgery, New York University School of Medicine (J.S.B.); AstraZeneca Gothenburg, Mölndal, Sweden (P.H., J.B., M.M.); AstraZeneca Gaithersburg, MD (B.G.K.); Stanford Center for Clinical Research, Stanford University School of Medicine, CA (K.W.M.); Faculty of Medicine and Health, Örebro University, Sweden (L.N.); and Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, UK (F.G.R.F.).
authors.forename: Michael S
authors.initials: MS
authors.lastname: Conte
authors.affiliation: From Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC (W.S.J., G.H., C.R., M.P.P.); Swiss Cardiovascular Centre, Inselspital, Bern University Hospital, University of Bern, Switzerland (I.B.); University of Colorado School of Medicine and CPC Clinical Research, Aurora (W.R.H.); Department of Surgery, University of California San Francisco (M.S.C.); Department of Cardiology, Ochsner Clinical School, University of Queensland, Australia (C.J.W.); Ochsner Medical Center, New Orleans, LA (C.J.W.); Departments of Medicine and Surgery, New York University School of Medicine (J.S.B.); AstraZeneca Gothenburg, Mölndal, Sweden (P.H., J.B., M.M.); AstraZeneca Gaithersburg, MD (B.G.K.); Stanford Center for Clinical Research, Stanford University School of Medicine, CA (K.W.M.); Faculty of Medicine and Health, Örebro University, Sweden (L.N.); and Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, UK (F.G.R.F.).
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: White
authors.affiliation: From Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC (W.S.J., G.H., C.R., M.P.P.); Swiss Cardiovascular Centre, Inselspital, Bern University Hospital, University of Bern, Switzerland (I.B.); University of Colorado School of Medicine and CPC Clinical Research, Aurora (W.R.H.); Department of Surgery, University of California San Francisco (M.S.C.); Department of Cardiology, Ochsner Clinical School, University of Queensland, Australia (C.J.W.); Ochsner Medical Center, New Orleans, LA (C.J.W.); Departments of Medicine and Surgery, New York University School of Medicine (J.S.B.); AstraZeneca Gothenburg, Mölndal, Sweden (P.H., J.B., M.M.); AstraZeneca Gaithersburg, MD (B.G.K.); Stanford Center for Clinical Research, Stanford University School of Medicine, CA (K.W.M.); Faculty of Medicine and Health, Örebro University, Sweden (L.N.); and Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, UK (F.G.R.F.).
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Berger
authors.affiliation: From Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC (W.S.J., G.H., C.R., M.P.P.); Swiss Cardiovascular Centre, Inselspital, Bern University Hospital, University of Bern, Switzerland (I.B.); University of Colorado School of Medicine and CPC Clinical Research, Aurora (W.R.H.); Department of Surgery, University of California San Francisco (M.S.C.); Department of Cardiology, Ochsner Clinical School, University of Queensland, Australia (C.J.W.); Ochsner Medical Center, New Orleans, LA (C.J.W.); Departments of Medicine and Surgery, New York University School of Medicine (J.S.B.); AstraZeneca Gothenburg, Mölndal, Sweden (P.H., J.B., M.M.); AstraZeneca Gaithersburg, MD (B.G.K.); Stanford Center for Clinical Research, Stanford University School of Medicine, CA (K.W.M.); Faculty of Medicine and Health, Örebro University, Sweden (L.N.); and Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, UK (F.G.R.F.).
authors.forename: Peter
authors.initials: P
authors.lastname: Held
authors.affiliation: From Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC (W.S.J., G.H., C.R., M.P.P.); Swiss Cardiovascular Centre, Inselspital, Bern University Hospital, University of Bern, Switzerland (I.B.); University of Colorado School of Medicine and CPC Clinical Research, Aurora (W.R.H.); Department of Surgery, University of California San Francisco (M.S.C.); Department of Cardiology, Ochsner Clinical School, University of Queensland, Australia (C.J.W.); Ochsner Medical Center, New Orleans, LA (C.J.W.); Departments of Medicine and Surgery, New York University School of Medicine (J.S.B.); AstraZeneca Gothenburg, Mölndal, Sweden (P.H., J.B., M.M.); AstraZeneca Gaithersburg, MD (B.G.K.); Stanford Center for Clinical Research, Stanford University School of Medicine, CA (K.W.M.); Faculty of Medicine and Health, Örebro University, Sweden (L.N.); and Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, UK (F.G.R.F.).
authors.forename: Brian G
authors.initials: BG
authors.lastname: Katona
authors.affiliation: From Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC (W.S.J., G.H., C.R., M.P.P.); Swiss Cardiovascular Centre, Inselspital, Bern University Hospital, University of Bern, Switzerland (I.B.); University of Colorado School of Medicine and CPC Clinical Research, Aurora (W.R.H.); Department of Surgery, University of California San Francisco (M.S.C.); Department of Cardiology, Ochsner Clinical School, University of Queensland, Australia (C.J.W.); Ochsner Medical Center, New Orleans, LA (C.J.W.); Departments of Medicine and Surgery, New York University School of Medicine (J.S.B.); AstraZeneca Gothenburg, Mölndal, Sweden (P.H., J.B., M.M.); AstraZeneca Gaithersburg, MD (B.G.K.); Stanford Center for Clinical Research, Stanford University School of Medicine, CA (K.W.M.); Faculty of Medicine and Health, Örebro University, Sweden (L.N.); and Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, UK (F.G.R.F.).
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Mahaffey
authors.affiliation: From Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC (W.S.J., G.H., C.R., M.P.P.); Swiss Cardiovascular Centre, Inselspital, Bern University Hospital, University of Bern, Switzerland (I.B.); University of Colorado School of Medicine and CPC Clinical Research, Aurora (W.R.H.); Department of Surgery, University of California San Francisco (M.S.C.); Department of Cardiology, Ochsner Clinical School, University of Queensland, Australia (C.J.W.); Ochsner Medical Center, New Orleans, LA (C.J.W.); Departments of Medicine and Surgery, New York University School of Medicine (J.S.B.); AstraZeneca Gothenburg, Mölndal, Sweden (P.H., J.B., M.M.); AstraZeneca Gaithersburg, MD (B.G.K.); Stanford Center for Clinical Research, Stanford University School of Medicine, CA (K.W.M.); Faculty of Medicine and Health, Örebro University, Sweden (L.N.); and Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, UK (F.G.R.F.).
authors.forename: Lars
authors.initials: L
authors.lastname: Norgren
authors.affiliation: From Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC (W.S.J., G.H., C.R., M.P.P.); Swiss Cardiovascular Centre, Inselspital, Bern University Hospital, University of Bern, Switzerland (I.B.); University of Colorado School of Medicine and CPC Clinical Research, Aurora (W.R.H.); Department of Surgery, University of California San Francisco (M.S.C.); Department of Cardiology, Ochsner Clinical School, University of Queensland, Australia (C.J.W.); Ochsner Medical Center, New Orleans, LA (C.J.W.); Departments of Medicine and Surgery, New York University School of Medicine (J.S.B.); AstraZeneca Gothenburg, Mölndal, Sweden (P.H., J.B., M.M.); AstraZeneca Gaithersburg, MD (B.G.K.); Stanford Center for Clinical Research, Stanford University School of Medicine, CA (K.W.M.); Faculty of Medicine and Health, Örebro University, Sweden (L.N.); and Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, UK (F.G.R.F.).
authors.forename: Juuso
authors.initials: J
authors.lastname: Blomster
authors.affiliation: From Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC (W.S.J., G.H., C.R., M.P.P.); Swiss Cardiovascular Centre, Inselspital, Bern University Hospital, University of Bern, Switzerland (I.B.); University of Colorado School of Medicine and CPC Clinical Research, Aurora (W.R.H.); Department of Surgery, University of California San Francisco (M.S.C.); Department of Cardiology, Ochsner Clinical School, University of Queensland, Australia (C.J.W.); Ochsner Medical Center, New Orleans, LA (C.J.W.); Departments of Medicine and Surgery, New York University School of Medicine (J.S.B.); AstraZeneca Gothenburg, Mölndal, Sweden (P.H., J.B., M.M.); AstraZeneca Gaithersburg, MD (B.G.K.); Stanford Center for Clinical Research, Stanford University School of Medicine, CA (K.W.M.); Faculty of Medicine and Health, Örebro University, Sweden (L.N.); and Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, UK (F.G.R.F.).
authors.forename: Marcus
authors.initials: M
authors.lastname: Millegård
authors.affiliation: From Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC (W.S.J., G.H., C.R., M.P.P.); Swiss Cardiovascular Centre, Inselspital, Bern University Hospital, University of Bern, Switzerland (I.B.); University of Colorado School of Medicine and CPC Clinical Research, Aurora (W.R.H.); Department of Surgery, University of California San Francisco (M.S.C.); Department of Cardiology, Ochsner Clinical School, University of Queensland, Australia (C.J.W.); Ochsner Medical Center, New Orleans, LA (C.J.W.); Departments of Medicine and Surgery, New York University School of Medicine (J.S.B.); AstraZeneca Gothenburg, Mölndal, Sweden (P.H., J.B., M.M.); AstraZeneca Gaithersburg, MD (B.G.K.); Stanford Center for Clinical Research, Stanford University School of Medicine, CA (K.W.M.); Faculty of Medicine and Health, Örebro University, Sweden (L.N.); and Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, UK (F.G.R.F.).
authors.forename: Craig
authors.initials: C
authors.lastname: Reist
authors.affiliation: From Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC (W.S.J., G.H., C.R., M.P.P.); Swiss Cardiovascular Centre, Inselspital, Bern University Hospital, University of Bern, Switzerland (I.B.); University of Colorado School of Medicine and CPC Clinical Research, Aurora (W.R.H.); Department of Surgery, University of California San Francisco (M.S.C.); Department of Cardiology, Ochsner Clinical School, University of Queensland, Australia (C.J.W.); Ochsner Medical Center, New Orleans, LA (C.J.W.); Departments of Medicine and Surgery, New York University School of Medicine (J.S.B.); AstraZeneca Gothenburg, Mölndal, Sweden (P.H., J.B., M.M.); AstraZeneca Gaithersburg, MD (B.G.K.); Stanford Center for Clinical Research, Stanford University School of Medicine, CA (K.W.M.); Faculty of Medicine and Health, Örebro University, Sweden (L.N.); and Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, UK (F.G.R.F.).
authors.forename: Manesh R
authors.initials: MR
authors.lastname: Patel
authors.affiliation: From Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC (W.S.J., G.H., C.R., M.P.P.); Swiss Cardiovascular Centre, Inselspital, Bern University Hospital, University of Bern, Switzerland (I.B.); University of Colorado School of Medicine and CPC Clinical Research, Aurora (W.R.H.); Department of Surgery, University of California San Francisco (M.S.C.); Department of Cardiology, Ochsner Clinical School, University of Queensland, Australia (C.J.W.); Ochsner Medical Center, New Orleans, LA (C.J.W.); Departments of Medicine and Surgery, New York University School of Medicine (J.S.B.); AstraZeneca Gothenburg, Mölndal, Sweden (P.H., J.B., M.M.); AstraZeneca Gaithersburg, MD (B.G.K.); Stanford Center for Clinical Research, Stanford University School of Medicine, CA (K.W.M.); Faculty of Medicine and Health, Örebro University, Sweden (L.N.); and Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, UK (F.G.R.F.). schuyler.jones@duke.edu.
authors.forename: F Gerry R
authors.initials: FG
authors.lastname: Fowkes
mesh_terms: D000241:Adenosine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000368:Aged; D000077144:Clopidogrel; D005260:Female; D006801:Humans; D035002:Lower Extremity / Q000098:blood supply*; D008297:Male; D058729:Peripheral Arterial Disease / Q000188:drug therapy* / Q000473:pathology; D058921:Purinergic P2Y Receptor Antagonists / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000077486:Ticagrelor; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D058921:Purinergic P2Y Receptor Antagonists; D000077144:Clopidogrel; D000077486:Ticagrelor; D000241:Adenosine; D013988:Ticlopidine
keywords: lower extremity revascularization; peripheral artery disease; ticagrelor; vascular intervention