Risk of stroke in patients with high on-clopidogrel platelet reactivity to adenosine diphosphate after percutaneous coronary intervention

Am J Cardiol. 2014 Jun 1;113(11):1807-14. doi: 10.1016/j.amjcard.2014.03.009. Epub 2014 Mar 15.


Several prospective studies have shown that high on-clopidogrel platelet reactivity (HPR) in patients undergoing percutaneous coronary intervention (PCI) is a risk factor for ischemic events. All studies were insufficiently powered to detect differences in stroke between patients with HPR and those without. Therefore, we performed a systematic review and meta-analysis of available publications aimed at determining whether patients undergoing PCI with HPR are also at increased risk of stroke. We searched for prospective studies enrolling patients undergoing PCI and treated with aspirin and clopidogrel that reported on clinical relevance of HPR to adenosine diphosphate. Study end point was the rate of stroke. We also investigated whether there was an interaction on the relative risk of stroke between HPR, clinical presentation, duration of follow-up, or laboratory methods. Fourteen studies including 11,959 patients were deemed eligible. On pooled analysis, the risk of stroke was higher in patients with HPR compared with patients with no HPR (1.2% vs 0.7%, relative risk on fixed effect 1.84, 95% confidence interval 1.21 to 2.80). There was no heterogeneity among the studies (I(2) = 0%, p = 0.5). Clinical presentation (p = 0.39 for interaction), duration of follow-up (p = 0.87 for interaction), and laboratory method for detection of HPR (p = 0.99 for interaction) did not affect the relative increase in the risk of stroke in patients with HPR compared with patients with no HPR. In conclusion, in patients with coronary artery disease undergoing PCI, the presence of HPR to adenosine diphosphate is a risk factor for stroke.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Adenosine Diphosphate / administration & dosage*
  • Blood Platelets / drug effects*
  • Clopidogrel
  • Dose-Response Relationship, Drug
  • Global Health
  • Humans
  • Incidence
  • Myocardial Ischemia / blood
  • Myocardial Ischemia / therapy*
  • Percutaneous Coronary Intervention*
  • Platelet Aggregation / drug effects*
  • Platelet Aggregation Inhibitors / administration & dosage
  • Platelet Function Tests
  • Postoperative Period
  • Risk Factors
  • Stroke* / blood
  • Stroke* / epidemiology
  • Stroke* / etiology
  • Ticlopidine / administration & dosage
  • Ticlopidine / analogs & derivatives*


  • Platelet Aggregation Inhibitors
  • Adenosine Diphosphate
  • Clopidogrel
  • Ticlopidine