title: Prior smoking status, clinical outcomes, and the comparison of ticagrelor with clopidogrel in acute coronary syndromes-insights from the PLATelet inhibition and patient Outcomes (PLATO) trial.
abstract: BACKGROUND
  Habitual smoking has been associated with increased platelet reactivity, increased risk of thrombotic complications and greater efficacy of clopidogrel therapy over placebo. In the PLATO trial, ticagrelor compared to clopidogrel in patients with acute coronary syndromes (ACS) reduced the primary composite end point of vascular death, myocardial infarction and stroke, without increasing overall rates of major bleeding. We evaluated the results in relation to smoking habits.
  
  
  METHODS
  Interactions between habitual smokers (n = 6678) and in ex/nonsmokers (n = 11,932) and the effects of randomized treatments on ischemic and bleeding outcomes were evaluated by Cox regression analyses.
  
  
  RESULTS
  Habitual smokers had an overall lower risk profile and more often ST-elevation ACS. After adjustment for baseline imbalances, habitual smoking was associated with a higher incidence of definite stent thrombosis (adjusted HR, 1.44 [95% CI, 1.07-1.94]); there were no significant associations with other ischemic or bleeding end points. The effects of ticagrelor compared to clopidogrel were consistent for all outcomes regardless of smoking status. Thus, there was a similar reduction in the primary composite end point for habitual smokers (adjusted HR, 0.83 [95% CI, 0.68-1.00]) and ex/nonsmokers (adjusted HR, 0.89 [95% CI, 0.79-1.00]) (interaction P = .50), and in definite stent thrombosis for habitual smokers (adjusted HR, 0.59 [0.39-0.91]) and ex/nonsmokers (adjusted HR, 0.69 [95% CI, 0.45-1.07]) (interaction P = .61).
  
  
  CONCLUSIONS
  In patients hospitalized with ACS, habitual smoking is associated with a greater risk of subsequent stent thrombosis. The reduction of vascular death, myocardial infarction, stroke, and stent thrombosis by ticagrelor compared to clopidogrel is consistent regardless of smoking habits.
authors.affiliation: Medisch Centrum Alkmaar, The Netherlands. j.h.cornel@mca.nl
authors.forename: Jan H
authors.initials: JH
authors.lastname: Cornel
authors.forename: Richard C
authors.initials: RC
authors.lastname: Becker
authors.forename: Shaun G
authors.initials: SG
authors.lastname: Goodman
authors.forename: Steen
authors.initials: S
authors.lastname: Husted
authors.forename: Hugo
authors.initials: H
authors.lastname: Katus
authors.forename: Anwar
authors.initials: A
authors.lastname: Santoso
authors.forename: Gabriel
authors.initials: G
authors.lastname: Steg
authors.forename: Robert F
authors.initials: RF
authors.lastname: Storey
authors.forename: Marius
authors.initials: M
authors.lastname: Vintila
authors.forename: Jie L
authors.initials: JL
authors.lastname: Sun
authors.forename: Jay
authors.initials: J
authors.lastname: Horrow
authors.forename: Lars
authors.initials: L
authors.lastname: Wallentin
authors.forename: Robert
authors.initials: R
authors.lastname: Harrington
authors.forename: Stefan
authors.initials: S
authors.lastname: James
mesh_terms: D054058:Acute Coronary Syndrome / Q000188:drug therapy*; D000241:Adenosine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000368:Aged; D000077144:Clopidogrel; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D058921:Purinergic P2Y Receptor Antagonists / Q000008:administration & dosage*; D012307:Risk Factors; D012907:Smoking / Q000453:epidemiology*; D015607:Stents; D013927:Thrombosis / Q000453:epidemiology; D000077486:Ticagrelor; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D016896:Treatment Outcome
chemical_list: D010975:Platelet Aggregation Inhibitors; D058921:Purinergic P2Y Receptor Antagonists; D000077144:Clopidogrel; D000077486:Ticagrelor; D000241:Adenosine; D013988:Ticlopidine