title: Ticagrelor effects on myocardial infarction and the impact of event adjudication in the PLATO (Platelet Inhibition and Patient Outcomes) trial.
abstract: OBJECTIVE
  This study sought to report the treatment effect of ticagrelor on myocardial infarction (MI) and the strategy for and impact of event adjudication in the PLATO (Platelet Inhibition and Patient Outcomes) trial.
  
  
  BACKGROUND
  In PLATO, ticagrelor reduced cardiovascular death, MI, or stroke in patients with acute coronary syndromes (ACS).
  
  
  METHODS
  A clinical events committee (CEC) prospectively defined and adjudicated all suspected MI events, on the basis of events reported by investigators and by triggers on biomarkers. Treatment comparisons used CEC-adjudicated data, and per protocol, excluded silent MI.
  
  
  RESULTS
  Overall, 1,299 (610 ticagrelor, 689 clopidogrel) MIs reported by the CEC occurred during the trial. Of these, 1,097 (504 ticagrelor, 593 clopidogrel) contributed to the primary composite endpoint. Site investigators reported 1,198 (580 ticagrelor, 618 clopidogrel) MIs. Ticagrelor significantly reduced overall MI rates (12-month CEC-adjudicated Kaplan-Meier rates: 5.8% ticagrelor, 6.9% clopidogrel; hazard ratio [HR]: 0.84; 95% confidence interval [CI]: 0.75 to 0.95). Nonprocedural MI (HR: 0.86; 95% CI: 0.74 to 1.01) and MI related to percutaneous coronary intervention or stent thrombosis tended to be lower with ticagrelor. MIs related to coronary artery bypass graft surgery were few, but numerical excess was observed in patients assigned ticagrelor. Analyses of overall MIs using investigator-reported data showed similar results but did not reach statistical significance (HR: 0.88; 95% CI: 0.78 to 1.00).
  
  
  CONCLUSIONS
  In patients with ACS, ticagrelor significantly reduced the incidence of MI compared with clopidogrel, with consistent results across most MI subtypes. CEC procedures identified more MI endpoints compared with site investigators. (A Comparison of Ticagrelor [AZD6140] and Clopidogrel in Patients With Acute Coronary Syndrome [PLATO]; NCT00391872).
authors.affiliation: Duke Clinical Research Institute, Duke University, Durham, North Carolina; Department of Medicine, Stanford University, Stanford, California. Electronic address: kenneth.mahaffey@stanford.edu.
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Mahaffey
authors.affiliation: Department of Medical Sciences, Cardiology and Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
authors.forename: Claes
authors.initials: C
authors.lastname: Held
authors.affiliation: Duke Clinical Research Institute, Duke University, Durham, North Carolina.
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Wojdyla
authors.affiliation: Department of Medical Sciences, Cardiology and Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
authors.forename: Stefan K
authors.initials: SK
authors.lastname: James
authors.affiliation: Medizinishe Klinik, University of Heidelberg, Heidelberg, Germany.
authors.forename: Hugo A
authors.initials: HA
authors.lastname: Katus
authors.affiliation: Medical Department, Hospital Unit West, Herning/Holstbro, Denmark.
authors.forename: Steen
authors.initials: S
authors.lastname: Husted
authors.affiliation: INSERM-Unité 698, Paris, France; Assistance Publique-Hôpitaux de Paris, Département Hospitalo-Universitaire FIRE, Hôpital Bichat, Paris, France; Université Paris-Diderot, Sorbonne-Paris Cité, Paris, France.
authors.forename: Philippe Gabriel
authors.initials: PG
authors.lastname: Steg
authors.affiliation: TIMI Study Group, Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Cannon
authors.affiliation: Duke Clinical Research Institute, Duke University, Durham, North Carolina.
authors.forename: Richard C
authors.initials: RC
authors.lastname: Becker
authors.affiliation: Department of Cardiovascular Science, University of Sheffield, Sheffield, United Kingdom.
authors.forename: Robert F
authors.initials: RF
authors.lastname: Storey
authors.affiliation: AstraZeneca Research and Development, Wilmington, Delaware.
authors.forename: Nardev S
authors.initials: NS
authors.lastname: Khurmi
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: Prince of Wales Hospital, Institute of Vascular Medicine, the Chinese University of Hong Kong, Hong Kong.
authors.forename: Cheuk-Man
authors.initials: CM
authors.lastname: Yu
authors.affiliation: Azienda Ospedaliero Universitaria di Parma, Parma, Italy.
authors.forename: Diego
authors.initials: D
authors.lastname: Ardissino
authors.affiliation: Postgraduate Medical School, Grochowski Hospital, Warsaw, Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Budaj
authors.affiliation: Santo Andrés Hospital, Leiria, Portugal.
authors.forename: Joao
authors.initials: J
authors.lastname: Morais
authors.affiliation: Duke Clinical Research Institute, Duke University, Durham, North Carolina.
authors.forename: Debra
authors.initials: D
authors.lastname: Montgomery
authors.affiliation: AstraZeneca Research and Development, Mölndal, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Himmelmann
authors.affiliation: Department of Medicine, Stanford University, Stanford, California.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Harrington
authors.affiliation: Department of Medical Sciences, Cardiology and Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Wallentin
mesh_terms: D054058:Acute Coronary Syndrome / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D000241:Adenosine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000368:Aged; D001792:Blood Platelets / Q000187:drug effects*; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D014943:Global Health; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology* / Q000209:etiology / Q000517:prevention & control; D011446:Prospective Studies; D058921:Purinergic P2Y Receptor Antagonists / Q000008:administration & dosage; D015996:Survival Rate / Q000639:trends; D000077486:Ticagrelor; D016896:Treatment Outcome
chemical_list: D058921:Purinergic P2Y Receptor Antagonists; D000077486:Ticagrelor; D000241:Adenosine
keywords: acute coronary syndrome(s); adjudication; clinical events committee; clopidogrel; myocardial infarction; outcomes; ticagrelor