title: Ticagrelor vs. clopidogrel in patients with non-ST-elevation acute coronary syndrome with or without revascularization: results from the PLATO trial.
abstract: OBJECTIVE
  The optimal platelet inhibition strategy for ACS patients managed without revascularization is unknown. We aimed to evaluate efficacy and safety of ticagrelor vs. clopidogrel in the non-ST-elevation acute coronary syndrome (NSTE-ACS) subgroup of the PLATO trial, in the total cohort, and in the subgroups managed with and without revascularization within 10 days of randomization.
  
  
  RESULTS
  We performed a retrospective analysis of the primary endpoint of cardiovascular death/myocardial infarction/stroke. Among 18 624 PLATO patients, 11 080 (59%) were categorized as NSTE-ACS at randomization. During the initial 10 days, 74% had angiography, 46% PCI, and 5% CABG. In NSTE-ACS patients, the primary endpoint was reduced with ticagrelor vs. clopidogrel [10.0 vs. 12.3%; hazard ratio (HR) 0.83; 95% confidence interval (CI) = 0.74-0.93], as was myocardial infarction (6.6 vs. 7.7%; HR 0.86; 95% CI = 0.74-0.99), cardiovascular death (3.7 vs. 4.9%; HR 0.77; 95% CI = 0.64-0.93), and all-cause death (4.3 vs. 5.8%; HR 0.76; 95% CI = 0.64-0.90). Major bleeding rate was similar between treatment groups (13.4 vs. 12.6%; HR 1.07; 95% CI = 0.95-1.19), but ticagrelor was associated with an increase in non-CABG major bleeding (4.8 vs. 3.8%; HR 1.28; 95% CI = 1.05-1.56). Within the first 10 days, 5366 (48.4%) patients were managed without revascularization. Regardless of revascularization or not, ticagrelor consistently reduced the primary outcome (HR 0.86 vs. 0.85, interaction P = 0.93), and all-cause death (HR 0.75 vs. 0.73, interaction P = 0.89) with no significant increase in overall major bleeding.
  
  
  CONCLUSIONS
  In patients with NSTE-ACS, benefit of ticagrelor over clopidogrel in reducing ischaemic events and total mortality was consistent with the overall PLATO trial, independent of actually performed revascularization during the initial 10 days.
authors.affiliation: Department of Medical Sciences, Cardiology and Uppsala Clinical Research Center, Uppsala University, MTC Building, Uppsala Science Park, Dag Hammarskjölds väg 14B, SE-752 37 Uppsala, Sweden.
authors.forename: Daniel
authors.initials: D
authors.lastname: Lindholm
authors.affiliation: Department of Medical Sciences, Cardiology and Uppsala Clinical Research Center, Uppsala University, MTC Building, Uppsala Science Park, Dag Hammarskjölds väg 14B, SE-752 37 Uppsala, Sweden.
authors.forename: Christoph
authors.initials: C
authors.lastname: Varenhorst
authors.affiliation: TIMI Study Group, Brigham and Women's Hospital, Boston, MA, USA.
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Cannon
authors.affiliation: Department of Medicine, Stanford University, Stanford, CA, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Harrington
authors.affiliation: AstraZeneca Research and Development, Mölndal, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Himmelmann
authors.affiliation: AstraZeneca Research and Development, Wilmington, DE, USA.
authors.forename: Juan
authors.initials: J
authors.lastname: Maya
authors.affiliation: Medical Department, Hospital Unit West, Herning/Holstbro, Denmark.
authors.forename: Steen
authors.initials: S
authors.lastname: Husted
authors.affiliation: INSERM-Unité 1148, Paris, France Assistance Publique-Hôpitaux de Paris, Département Hospitalo-Universitaire FIRE, Hôpital Bichat, Paris, France NHLI Imperial College, ICMS, Royal Brompton Hospital, London, UK Université Paris-Diderot, Sorbonne-Paris Cité, Paris, France.
authors.forename: Philippe Gabriel
authors.initials: PG
authors.lastname: Steg
authors.affiliation: Department of Cardiology, Medisch Centrum Alkmaar, Alkmaar, The Netherlands.
authors.forename: Jan H
authors.initials: JH
authors.lastname: Cornel
authors.affiliation: Department of Cardiovascular Science, University of Sheffield, Sheffield, UK.
authors.forename: Robert F
authors.initials: RF
authors.lastname: Storey
authors.affiliation: Duke Clinical Research Institute, Duke University Medical Center, Durham, NC, USA.
authors.forename: Susanna R
authors.initials: SR
authors.lastname: Stevens
authors.affiliation: Department of Medical Sciences, Cardiology and Uppsala Clinical Research Center, Uppsala University, MTC Building, Uppsala Science Park, Dag Hammarskjölds väg 14B, SE-752 37 Uppsala, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Wallentin
authors.affiliation: Department of Medical Sciences, Cardiology and Uppsala Clinical Research Center, Uppsala University, MTC Building, Uppsala Science Park, Dag Hammarskjölds väg 14B, SE-752 37 Uppsala, Sweden stefan.james@ucr.uu.se.
authors.forename: Stefan K
authors.initials: SK
authors.lastname: James
mesh_terms: D054058:Acute Coronary Syndrome / Q000188:drug therapy* / Q000401:mortality; D000241:Adenosine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000368:Aged; D000077144:Clopidogrel; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D009203:Myocardial Infarction / Q000209:etiology / Q000401:mortality; D009204:Myocardial Revascularization / Q000401:mortality / Q000706:statistics & numerical data; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D012189:Retrospective Studies; D000077486:Ticagrelor; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D000077486:Ticagrelor; D000241:Adenosine; D013988:Ticlopidine
keywords: Acute coronary syndrome; Platelet inhibition
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