title: Comparison of ticagrelor, the first reversible oral P2Y(12) receptor antagonist, with clopidogrel in patients with acute coronary syndromes: Rationale, design, and baseline characteristics of the PLATelet inhibition and patient Outcomes (PLATO) trial.
abstract: BACKGROUND
  Antiplatelet therapy is essential treatment for acute coronary syndromes (ACS). Current therapies, however, have important limitations affecting their clinical success. Ticagrelor, the first reversible oral P2Y(12) receptor antagonist, provides faster, greater, and more consistent adenosine diphosphate-receptor inhibition than clopidogrel. The phase III PLATelet inhibition and patient Outcomes (PLATO) trial is designed to test the hypothesis that ticagrelor compared with clopidogrel will result in a lower risk of recurrent thrombotic events in a broad patient population with ACS.
  
  
  METHODS
  PLATO is an international, randomized, double-blind, event-driven trial involving >18,000 patients hospitalized for ST-elevation ACS with scheduled primary percutaneous coronary intervention or for non-ST-elevation ACS. After loading doses of ticagrelor 180 mg or clopidogrel 300 mg in a double-blind, double-dummy fashion (with provision for additional 300 mg clopidogrel at percutaneous coronary intervention), patients will receive ticagrelor 90 mg twice daily or clopidogrel 75 mg once daily for 6 to 12 months on top of acetylsalicylic acid. The primary efficacy end point is time to first occurrence of death from vascular causes, myocardial infarction, or stroke. The primary safety variable is PLATO-defined major bleeding. An extensive substudy program will explore the pathophysiology of ACS, indicators of prognosis and response to treatment, mechanisms of effect and safety of the study medications, health economics, and quality of life.
  
  
  CONCLUSIONS
  The PLATO study will provide a pivotal comparison of the efficacy and safety of ticagrelor with those of clopidogrel in ACS patients, together with extensive information on treatment outcomes in different subsets of ACS in a broad patient population.
authors.affiliation: Uppsala Clinical Research Center, Sweden.
authors.forename: Stefan
authors.initials: S
authors.lastname: James
authors.forename: Axel
authors.initials: A
authors.lastname: Akerblom
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Cannon
authors.forename: Håkan
authors.initials: H
authors.lastname: Emanuelsson
authors.forename: Steen
authors.initials: S
authors.lastname: Husted
authors.forename: Hugo
authors.initials: H
authors.lastname: Katus
authors.forename: Allan
authors.initials: A
authors.lastname: Skene
authors.forename: Philippe Gabriel
authors.initials: PG
authors.lastname: Steg
authors.forename: Robert F
authors.initials: RF
authors.lastname: Storey
authors.forename: Robert
authors.initials: R
authors.lastname: Harrington
authors.forename: Richard
authors.initials: R
authors.lastname: Becker
authors.forename: Lars
authors.initials: L
authors.lastname: Wallentin