Platelet Function Testing in Patients with Acute Ischemic Stroke: An Observational Study

J Stroke Cerebrovasc Dis. 2017 Aug;26(8):1864-1873. doi: 10.1016/j.jstrokecerebrovasdis.2017.04.023. Epub 2017 May 30.

Abstract

Background: The measurement of platelet reactivity in patients with stroke undergoing antiplatelet therapies is not commonly performed in clinical practice. We assessed the prevalence of therapy responsiveness in patients with stroke and further investigated differences between patients on prevention therapy at stroke onset and patients naive to antiplatelet medications. We also sought differences in responsiveness between etiological subtypes and correlations between Clopidogrel responsiveness and genetic polymorphisms.

Methods: A total of 624 stroke patients on antiplatelet therapy were included. Two different groups were identified: "non-naive patients", and "naive patients". Platelet function was measured with multiple electrode aggregometry, and genotyping assays were used to determine CYP2C19 polymorphisms.

Results: Aspirin (ASA) responsiveness was significantly more frequent in naive patients compared with non-naive patients (94.9% versus 82.6%, P < .0010). A better responsiveness to ASA compared with Clopidogrel or combination therapy was found in the entire population (P < .0010), in non-naive patients (P < .0253), and in naive patients (P < .0010). Multivariate analysis revealed a strong effect of Clopidogrel as a possible "risk factor" for unresponsiveness (odds ratio 3.652, P < .0001). No difference between etiological subgroups and no correlations between responsiveness and CYP2C19 polymorphisms were found.

Conclusion: In our opinion, platelet function testing could be potentially useful in monitoring the biological effect of antiplatelet agents. A substantial proportion of patients with stroke on ASA were "resistant", and the treatment with Clopidogrel was accompanied by even higher rates of unresponsiveness. Longitudinal studies are needed to assess whether aggregometry might supply individualized prognostic information and whether it can be considered a valid tool for future prevention strategies.

Keywords: Ischemic stroke; aggregometry; platelet inhibitor; secondary prevention.

Publication types

  • Comparative Study
  • Observational Study

MeSH terms

  • Aged
  • Aged, 80 and over
  • Aspirin / adverse effects
  • Aspirin / therapeutic use*
  • Blood Platelets / drug effects*
  • Blood Platelets / enzymology
  • Brain Ischemia / blood
  • Brain Ischemia / diagnosis
  • Brain Ischemia / drug therapy*
  • Chi-Square Distribution
  • Clopidogrel
  • Cross-Sectional Studies
  • Cytochrome P-450 CYP2C19 / genetics
  • Cytochrome P-450 CYP2C19 / metabolism
  • Drug Resistance
  • Drug Therapy, Combination
  • Female
  • Humans
  • Logistic Models
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Odds Ratio
  • Pharmacogenetics
  • Pharmacogenomic Testing
  • Pharmacogenomic Variants
  • Platelet Aggregation / drug effects*
  • Platelet Aggregation Inhibitors / adverse effects
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Platelet Function Tests*
  • Polymorphism, Genetic
  • Predictive Value of Tests
  • Risk Factors
  • Stroke / blood
  • Stroke / diagnosis
  • Stroke / drug therapy*
  • Ticlopidine / adverse effects
  • Ticlopidine / analogs & derivatives*
  • Ticlopidine / therapeutic use
  • Treatment Outcome

Substances

  • Platelet Aggregation Inhibitors
  • Clopidogrel
  • CYP2C19 protein, human
  • Cytochrome P-450 CYP2C19
  • Ticlopidine
  • Aspirin