title: Association between smoking, outcomes, and early clopidogrel use in patients with acute coronary syndrome: insights from the Global Registry of Acute Coronary Events.
abstract: BACKGROUND
  Smoking induces CYP1A2, thereby enhancing clopidogrel conversion to its active metabolite. We sought to determine the association between clopidogrel use and clinical outcomes in smokers versus nonsmokers with a broad spectrum of acute coronary syndrome (ACS).
  
  
  METHODS
  We examined the association between early clopidogrel use in-hospital and 6-month outcomes among 44,426 patients with ACS in relation to smoking status in the Global Registry of Acute Coronary Events. We tested for heterogeneity of clopidogrel effect among smokers versus nonsmokers in separate multivariable models that adjusted for (1) established prognosticators in the Global Registry of Acute Coronary Events risk score and (2) independent predictors of major bleeding.
  
  
  RESULTS
  Rates of in-hospital mortality, death/myocardial infarction, and major bleeding were 4.3%, 5.9%, and 2.5%, respectively. Current smokers (n = 12,149) were more likely to be younger men without documented vascular disease; had lower rates of hypertension, hyperlipidemia, and diabetes; and more frequently presented with ST elevation (all P < .0001). Early clopidogrel use (55%) was associated with a reduction in the composite endpoint of mortality and myocardial infarction both in-hospital and at 6 months among current smokers and nonsmokers. There was no interaction between current smoking and clopidogrel use for ischemic endpoints. Major bleeding associated with early clopidogrel use was actually lower among current smokers compared with nonsmokers.
  
  
  CONCLUSIONS
  Despite prior observations of smoking-enhanced clopidogrel effects, early clopidogrel use among smokers presenting with ACS compared with nonsmokers was not independently associated with a greater reduction in cardiovascular events. In contrast with nonsmokers, clopidogrel use among smokers was not associated with excess bleeding, perhaps because of unmeasured confounders.
authors.affiliation: Division of Cardiology, Canadian Heart Research Center and Terrence Donnelly Heart Center, St Michael's Hospital, University of Toronto, Toronto, Ontario.
authors.forename: Matthew
authors.initials: M
authors.lastname: Sibbald
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Yan
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
authors.forename: Keith A A
authors.initials: KA
authors.lastname: Fox
authors.forename: Joel M
authors.initials: JM
authors.lastname: Gore
authors.forename: Ph Gabriel
authors.initials: PG
authors.lastname: Steg
authors.forename: Kim A
authors.initials: KA
authors.lastname: Eagle
authors.forename: David
authors.initials: D
authors.lastname: Brieger
authors.forename: Gilles
authors.initials: G
authors.lastname: Montalescot
authors.forename: Shaun G
authors.initials: SG
authors.lastname: Goodman
mesh_terms: D054058:Acute Coronary Syndrome / Q000175:diagnosis / Q000188:drug therapy / Q000453:epidemiology*; D000368:Aged; D000369:Aged, 80 and over; D000077144:Clopidogrel; D017023:Coronary Angiography; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D005500:Follow-Up Studies; D006470:Hemorrhage / Q000139:chemically induced / Q000453:epidemiology; D017052:Hospital Mortality / Q000639:trends; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D011379:Prognosis; D012042:Registries / Q000706:statistics & numerical data*; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects* / Q000453:epidemiology; D015996:Survival Rate / Q000639:trends; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013997:Time Factors
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine