Treatment Effect of Clopidogrel Plus Aspirin Within 12 Hours of Acute Minor Stroke or Transient Ischemic Attack

J Am Heart Assoc. 2016 Mar 21;5(3):e003038. doi: 10.1161/JAHA.115.003038.


Background: The aim of this study was to analyze the benefits and safety associated with the combination therapy of clopidogrel and aspirin among minor stroke or transient ischemic attack patients treated within 12 hours.

Methods and results: This was a subanalysis of the CHANCE (Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events) trial, mainly limited to the prespecified group of patients randomized within 12 hours to either the combination of clopidogrel plus aspirin or aspirin alone. The primary outcome was ischemic stroke during 90-day follow-up. Recurrent ischemic stroke and progressive ischemic stroke were analyzed. Multivariable Cox modeling showed that randomization within 12 hours was an independent predictor of ischemic stroke events (hazard ratio [95% CI] 1.25 [1.04-1.49], P=0.02). Among 2573 patients randomized within 12 hours, 282 (10.96%) patients had ischemic stroke events. Among them, 158 (12.34%) of 1280 patients taking aspirin experienced ischemic stroke compared with 124 (9.59%) of 1293 patients taking clopidogrel-aspirin (P=0.02). The dual antiplatelet was more effective than aspirin alone in reducing the risk of recurrent ischemic stroke (6.57% versus 8.91%, P=0.03) but not progressive ischemic stroke (3.02% versus 3.43%, P=0.28). There was no significant difference in hemorrhagic events (P=0.39).

Conclusions: Among patients treated within 12 hours, the combination of clopidogrel and aspirin was more effective than aspirin alone in reducing the risk of recurrent ischemic stroke during the 90-day follow-up and did not increase the hemorrhagic risk.

Clinical trial registration: URL: Unique identifier: NCT00979589.

Keywords: acute cerebral infarction; antiplatelets; transient ischemic attacks; trials.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aspirin / administration & dosage*
  • Aspirin / adverse effects
  • Chi-Square Distribution
  • China
  • Clopidogrel
  • Disease Progression
  • Double-Blind Method
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Female
  • Hemorrhage / chemically induced
  • Humans
  • Ischemic Attack, Transient / diagnosis
  • Ischemic Attack, Transient / drug therapy*
  • Ischemic Attack, Transient / mortality
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Platelet Aggregation Inhibitors / administration & dosage*
  • Platelet Aggregation Inhibitors / adverse effects
  • Proportional Hazards Models
  • Prospective Studies
  • Recurrence
  • Risk Factors
  • Secondary Prevention / methods*
  • Severity of Illness Index
  • Stroke / diagnosis
  • Stroke / drug therapy*
  • Ticlopidine / administration & dosage
  • Ticlopidine / adverse effects
  • Ticlopidine / analogs & derivatives*
  • Time Factors
  • Time-to-Treatment*
  • Treatment Outcome


  • Platelet Aggregation Inhibitors
  • Clopidogrel
  • Ticlopidine
  • Aspirin

Associated data