Effect of dual versus mono antiplatelet therapy on recurrent stroke modulated by activated partial thromboplastin time

Eur J Neurol. 2019 Sep;26(9):1168-e78. doi: 10.1111/ene.13961. Epub 2019 May 9.


Background and purpose: The efficacy of dual antiplatelet treatment may be modified by many factors. The aim was to assess whether the effect of clopidogrel plus aspirin versus aspirin alone on recurrent stroke would be affected by admission activated partial thromboplastin time (aPTT).

Methods: Data were derived from the Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events (CHANCE) trial. A total of 5074 patients were categorized into three groups based on the aPTT distribution according to the 15th and 85th percentile. The primary outcome was any stroke within 90 days. The interaction of aPTT with antiplatelet therapy on stroke risk was assessed with a Cox proportional hazards model with adjustment for covariates.

Results: In the high aPTT group (defined as ≥35.9 s), stroke occurred in 6.7% of patients in the clopidogrel-aspirin arm and 11.9% in the aspirin arm [adjusted hazard ratio (HR) 0.50; 95% confidence interval (CI) 0.29-0.85]. In the medium aPTT group (24.6-35.8 s), stroke occurred in 7.7% of patients in the clopidogrel-aspirin arm and 11.8% in the aspirin arm (adjusted HR 0.62; 95% CI 0.50-0.75). Furthermore, in the low aPTT group (≤24.5 s), stroke occurred in 11.2% of patients in the clopidogrel-aspirin arm and 9.9% in the aspirin arm (adjusted HR 1.07; 95% CI 0.65-1.62). The interaction P value of antiplatelet therapy with aPTT level at the cut-point of approximately 25 s or below was significant (P < 0.05).

Conclusions: Dual antiplatelet therapy was superior to single antiplatelet therapy in the high or medium aPTT group but not in the low aPTT group.

Trial registration: ClinicalTrials.gov NCT00979589.

Keywords: activated partial thromboplastin time; aspirin; clopidogrel; minor stroke; transient ischaemic attack.

Publication types

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

MeSH terms

  • Aged
  • Aspirin / administration & dosage
  • Aspirin / pharmacology*
  • Brain Ischemia / prevention & control*
  • Clopidogrel / administration & dosage
  • Clopidogrel / pharmacology*
  • Drug Therapy, Combination
  • Female
  • Humans
  • Male
  • Middle Aged
  • Outcome Assessment, Health Care*
  • Partial Thromboplastin Time*
  • Platelet Aggregation Inhibitors / administration & dosage
  • Platelet Aggregation Inhibitors / pharmacology*
  • Recurrence
  • Stroke / prevention & control*


  • Platelet Aggregation Inhibitors
  • Clopidogrel
  • Aspirin

Associated data

  • ClinicalTrials.gov/NCT00979589