title: Clopidogrel and ischemic stroke outcomes by smoking status: Smoker's paradox?
abstract: OBJECTIVE
  Active smokers with myocardial infarction were shown to have enhanced benefit with clopidogrel compared with aspirin. Whether this "paradox" exists in ischemic stroke patients is unknown. We aimed to investigate whether smoking status has a differential impact on the efficacy of clopidogrel vs. aspirin in patients with non-cardioembolic strokes.
  
  
  METHODS
  This single-center study retrospectively assessed 1792 non-cardioembolic ischemic stroke patients discharged from January 2013 to October 2014, and followed for 12months. Patients were categorized as current-smokers and never-smokers. Primary outcome was a composite of secondary ischemic stroke, myocardial infarction and all-cause death. Secondary outcome was secondary ischemic stroke.
  
  
  RESULTS
  1066 patients were current-smokers and 726 were never-smokers. Compared with never-smokers, current-smokers had significantly higher rates of ischemic stroke (4.3% vs. 1.2%; adjusted OR: 3.60, 95%CI: 1.50-8.64, p=0.004). Regarding the primary outcome, among smokers, rates showed a lower trend in clopidogrel vs. aspirin groups (3.7% vs. 6.4%; adjusted OR 0.57, 95%CI: 0.31-1.07, p=0.08), but no difference among never-smokers (2.1% vs. 1.0%; adjusted OR: 1.67, 95%CI: 0.47-5.89, p=0.42). Similarly, among smokers, trending lower rates for recurrent ischemic stroke were observed in clopidogrel vs. aspirin group (3.1% vs. 5.0%; adjusted OR: 0.60, 95%CI: 0.31-1.18, p=0.14); but no difference between the two groups among never-smokers (1.7% vs. 1.0%; adjusted OR 1.36, 95%CI: 0.36-5.52, p=0.65).
  
  
  CONCLUSIONS
  Smoking is a major risk factor for recurrent stroke in our retrospective non-cardioembolic ischemic stroke cohort. Active-smokers trend toward better cardiovascular outcomes when on clopidogrel. This finding needs to be confirmed in a prospective cohort.
authors.affiliation: Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China.
authors.forename: Haiqing
authors.initials: H
authors.lastname: Song
authors.affiliation: Evidence-Based Medicine Center, Xuanwu Hospital, Capital Medical University, Beijing 100053, China.
authors.forename: Chengbei
authors.initials: C
authors.lastname: Hou
authors.affiliation: Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China.
authors.forename: Qingyu
authors.initials: Q
authors.lastname: Cao
authors.affiliation: Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Dong
authors.affiliation: Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China.
authors.forename: Xiaoqin
authors.initials: X
authors.lastname: Huang
authors.affiliation: Department of Neurology, Medical University of South Carolina, Charleston, SC 29425, United States.
authors.forename: Wuwei
authors.initials: W
authors.lastname: Feng
authors.affiliation: Department of Neurology, Medical University of South Carolina, Charleston, SC 29425, United States.
authors.forename: Bruce
authors.initials: B
authors.lastname: Ovbiagele
authors.affiliation: Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China. Electronic address: wangmo-li@263.net.
authors.forename: Moli
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing 100053, China. Electronic address: jixm@ccmu.edu.cn.
authors.forename: Xunming
authors.initials: X
authors.lastname: Ji
mesh_terms: D001241:Aspirin / Q000627:therapeutic use*; D002545:Brain Ischemia / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D000077144:Clopidogrel; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000150:complications / Q000401:mortality; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D012008:Recurrence; D012189:Retrospective Studies; D012907:Smoking / Q000401:mortality; D020521:Stroke / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin
keywords: Aspirin; Clopidogrel; Ischemic stroke; Outcome; Smoking