Homocysteine Level Predicts Response to Dual Antiplatelet in Women With Minor Stroke or Transient Ischemic Attack: Subanalysis of the CHANCE Trial

Arterioscler Thromb Vasc Biol. 2020 Mar;40(3):839-846. doi: 10.1161/ATVBAHA.119.313741. Epub 2020 Jan 16.


Objectives: To investigate the relationship of homocysteine levels with the efficacy and safety of dual antiplatelet therapy in female and male patients. Approach and Results: The CHANCE trial (Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events) randomized patients with acute minor ischemic stroke or high-risk transient ischemic attack to clopidogrel plus aspirin or aspirin alone from October 1, 2009, to July 30, 2012, in China. A subgroup of 3044 consecutive patients with baseline homocysteine levels from 73 (64%) prespecified clinical sites was analyzed. Participants were grouped by sex. Primary outcome was stroke recurrence within 90 days. Secondary outcomes consisted of composite vascular events and independent living or death. Safety outcome was any bleeding. Cox proportional-hazards models were used to assess the interaction of homocysteine levels with randomized antiplatelet therapy on efficacy and safety outcomes. A significant interaction between homocysteine levels and the randomized antiplatelet therapies was found on recurrent stroke after adjustment for confounding factors in women (P=0.010) but not in men (P=0.595). Compared with aspirin alone, clopidogrel plus aspirin significantly reduced the risk of recurrent stroke in women without elevated homocysteine levels (adjusted hazard ratio, 0.459 [95% CI, 0.271-0.776]; P=0.004). Such benefit disappeared in female patients with increased homocysteine level. No significant interaction on functional outcome or bleeding rate was observed.

Conclusions: Homocysteine could be a potential biomarker to discriminate the effects of dual and single antiplatelet therapy in female patients with minor ischemic stroke or high-risk transient ischemic attack.

Clinical trial registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00979589.

Keywords: aspirin; cerebrovascular diseases; homocysteine; prognosis; stroke.

Publication types

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

MeSH terms

  • Aged
  • Aspirin / adverse effects
  • Aspirin / therapeutic use*
  • Biomarkers / blood
  • China / epidemiology
  • Clopidogrel / adverse effects
  • Clopidogrel / therapeutic use*
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Hemorrhage / chemically induced
  • Homocysteine / blood*
  • Humans
  • Hyperhomocysteinemia / blood*
  • Hyperhomocysteinemia / diagnosis
  • Hyperhomocysteinemia / epidemiology
  • Ischemic Attack, Transient / blood
  • Ischemic Attack, Transient / diagnosis
  • Ischemic Attack, Transient / drug therapy*
  • Ischemic Attack, Transient / epidemiology
  • Male
  • Middle Aged
  • Platelet Aggregation Inhibitors / adverse effects
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Recurrence
  • Risk Assessment
  • Risk Factors
  • Sex Factors
  • Stroke / blood
  • Stroke / diagnosis
  • Stroke / drug therapy*
  • Stroke / epidemiology
  • Time Factors
  • Treatment Outcome


  • Biomarkers
  • Platelet Aggregation Inhibitors
  • Homocysteine
  • Clopidogrel
  • Aspirin

Associated data

  • ClinicalTrials.gov/NCT00979589