title: Ticagrelor versus clopidogrel in patients with acute coronary syndromes undergoing coronary artery bypass surgery: results from the PLATO (Platelet Inhibition and Patient Outcomes) trial.
abstract: OBJECTIVE
  The purpose of this study is to evaluate the efficacy and safety of ticagrelor and clopidogrel in patients with acute coronary syndrome undergoing coronary artery bypass graft surgery (CABG), as a post-randomization strategy.
  
  
  BACKGROUND
  Ticagrelor is a novel, reversibly binding, oral, direct-acting P2Y(12)-receptor antagonist. In the PLATO (Platelet Inhibition and Patient Outcomes) trial, which randomized 18,624 patients with acute coronary syndromes, ticagrelor compared with clopidogrel significantly reduced the risk of the primary composite end point of cardiovascular (CV) death, myocardial infarction, or stroke (hazard ratio [HR]: 0.84; 95% confidence interval [CI]: 0.77 to 0.92; p < 0.001). This report investigated the outcomes of patients treated with CABG during the trial.
  
  
  METHODS
  In total, 1,899 patients underwent CABG post-randomization. The protocol recommended ticagrelor/placebo to be withheld for 24 to 72 h and clopidogrel/placebo for 5 days preoperatively. In all, 1,261 patients underwent CABG and were receiving study drug treatment <7 days before surgery. The statistical analysis was based on events occurring from the CABG procedure until the end of the study, excluding 3 patients with CABG after study end.
  
  
  RESULTS
  In the 1,261 patient cohort, the relative reduction of primary composite end point at 12 months (10.6% [66 of 629] with ticagrelor versus 13.1% [79 of 629] with clopidogrel; HR: 0.84; 95% CI: 0.60 to 1.16; p = 0.29) was consistent with the results of the whole trial. Total mortality was reduced from 9.7% (58 of 629) to 4.7% (29 of 629; HR: 0.49; 95% CI: 0.32 to 0.77; p < 0.01), CV death from 7.9% (47 of 629) to 4.1% (25 of 629; HR: 0.52; 95% CI: 0.32 to 0.85; p < 0.01), and non-CV death numerically from 2.0% to 0.7% (p = 0.07). There was no significant difference in CABG-related major bleeding between the randomized treatments.
  
  
  CONCLUSIONS
  In the subgroup of patients undergoing CABG within 7 days after the last study drug intake, ticagrelor compared with clopidogrel was associated with a substantial reduction in total and CV mortality without excess risk of CABG-related bleeding.
authors.affiliation: Uppsala Clinical Research Center, Department of Medical Sciences, Uppsala University, Sweden. claes.held@ucr.uu.se
authors.forename: Claes
authors.initials: C
authors.lastname: Held
authors.forename: Nils
authors.initials: N
authors.lastname: Asenblad
authors.forename: Jean Pierre
authors.initials: JP
authors.lastname: Bassand
authors.forename: Richard C
authors.initials: RC
authors.lastname: Becker
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Cannon
authors.forename: Marc J
authors.initials: MJ
authors.lastname: Claeys
authors.forename: Robert A
authors.initials: RA
authors.lastname: Harrington
authors.forename: Jay
authors.initials: J
authors.lastname: Horrow
authors.forename: Steen
authors.initials: S
authors.lastname: Husted
authors.forename: Stefan K
authors.initials: SK
authors.lastname: James
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Mahaffey
authors.forename: José C
authors.initials: JC
authors.lastname: Nicolau
authors.forename: Benjamin M
authors.initials: BM
authors.lastname: Scirica
authors.forename: Robert F
authors.initials: RF
authors.lastname: Storey
authors.forename: Marius
authors.initials: M
authors.lastname: Vintila
authors.forename: Joseph
authors.initials: J
authors.lastname: Ycas
authors.forename: Lars
authors.initials: L
authors.lastname: Wallentin
mesh_terms: D054058:Acute Coronary Syndrome / Q000188:drug therapy* / Q000401:mortality; D000241:Adenosine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000368:Aged; D000077144:Clopidogrel; D001026:Coronary Artery Bypass; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D019106:Postoperative Hemorrhage / Q000453:epidemiology*; D058921:Purinergic P2Y Receptor Antagonists / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D000077486:Ticagrelor; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D058921:Purinergic P2Y Receptor Antagonists; D000077144:Clopidogrel; D000077486:Ticagrelor; D000241:Adenosine; D013988:Ticlopidine