title: ASA failure: does the combination ASA/clopidogrel confer better long-term vascular protection?
abstract: OBJECTIVE
  To assess whether adding clopidogrel to acetylsalicylic acid (ASA) has a long-term protective vascular effect in patients with lacunar stroke while taking ASA.
  
  
  METHODS
  Post hoc analysis of 838 patients with ASA failure and recent lacunar stroke from the Secondary Prevention of Small Subcortical Strokes Trial (SPS3) cohort randomly allocated to aspirin (325 mg/day) and clopidogrel (75 mg/day) or placebo. Primary efficacy outcome was stroke recurrence (ischemic and intracranial hemorrhage) and main safety outcome was major extracranial hemorrhage. Patients were followed for a mean period of 3.5 years.
  
  
  RESULTS
  The ASA failure group had a significantly higher risk of vascular events including ischemic stroke when compared with the non-ASA failure group (n = 2,151) in SPS3 (p = 0.03). Mean age was 65.6 years and 65% were men. The risk of recurrent stroke was not reduced in the dual antiplatelet group, 3.1% per year, compared to the aspirin-only group, 3.3% per year (hazard ratio [HR] 0.91; 95% confidence interval [CI] 0.61-1.37). There was also no difference between groups for ischemic stroke (HR 0.90; 95% CI 0.59-1.38). The risk of gastrointestinal bleeding was higher in the dual antiplatelet group (HR 2.7; 95% CI 1.1-6.9); however, the risk of intracranial hemorrhage was not different.
  
  
  CONCLUSIONS
  In patients with a recent lacunar stroke while taking ASA, the addition of clopidogrel did not result in reduction of vascular events vs continuing ASA only.
  
  
  METHODS
  This study provides Class I evidence that for patients with recent lacunar stroke while taking ASA, adding clopidogrel as compared to continuing ASA alone does not reduce the risk of recurrent stroke.
authors.affiliation: From the Department of Neurology, Neurosurgery and Medicine (R.C.), McGill University, Montreal, Canada; Department of Biostatistics (Y.Z., L.A.M.), University of Alabama at Birmingham; Department of Medicine (Neurology) (R.G.H.), McMaster University, Hamilton, Canada; Hennepin County Medical Center (Neurology) (D.C.A.), University of Minnesota Medical School, Minneapolis; Department of Clinical Pharmacy (R.L.T.), University of Texas, Austin; and Department of Medicine (O.R.B.), Brain Research Center, University of British Columbia, Vancouver, Canada.
authors.forename: Robert
authors.initials: R
authors.lastname: Côté
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Robert G
authors.initials: RG
authors.lastname: Hart
authors.forename: Leslie A
authors.initials: LA
authors.lastname: McClure
authors.forename: David C
authors.initials: DC
authors.lastname: Anderson
authors.forename: Robert L
authors.initials: RL
authors.lastname: Talbert
authors.forename: Oscar R
authors.initials: OR
authors.lastname: Benavente
mesh_terms: D000368:Aged; D001241:Aspirin / Q000008:administration & dosage* / Q000627:therapeutic use; D000077144:Clopidogrel; D015331:Cohort Studies; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D059409:Stroke, Lacunar / Q000175:diagnosis / Q000453:epidemiology / Q000517:prevention & control*; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013997:Time Factors; D017211:Treatment Failure
chemical_list: D018696:Neuroprotective Agents; D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin