Association between high on-treatment platelet reactivity and occurrence of cerebral ischemic events in patients undergoing percutaneous coronary intervention

Thromb Res. 2016 Feb:138:49-54. doi: 10.1016/j.thromres.2015.12.021. Epub 2015 Dec 24.

Abstract

Introduction: Percutaneous coronary angioplasty (PCI) has become a routine treatment in symptomatic patients with coronary artery disease. The use of new generation drug eluting stents (DES) and dual antiplatelet therapy has significantly improved treatment outcomes and increased patients' safety by reducing the risk of stent thrombosis.

Aims: The goal of this study was to assess whether high on treatment platelet reactivity (HTPR), despite clopidogrel treatment, measured with Multiplate Electrode Aggregometer (MEA) is associated with the risk of adverse ischemic cerebral events.

Methods: Symptomatic patients with coronary artery disease admitted for coronary angiography and angioplasty (PCI) were consecutively enrolled in this study. 249 consecutive patients underwent coronary artery stenting for stable angina (n=215) or non-ST-elevation acute coronary syndrome (n=34). Inhibition of platelet aggregation was assessed by MEA. Genetic polymorphism of CYP2C19 was tested by HRM Real-Time PCR method in 150 patients.

Results: Patients with HTPR were more frequently diagnosed with ischemic stroke (p=0.0351, OR=16.818, 95% CI [1.464-193.23]) and other ischemic cerebral events (stroke or TIA, p=0.0339, OR=6.5, 95% CI [1.36-31.07]). Cumulative assessment of all ischemic and hemorrhagic events showed no statistical significance. Cerebral ischemic event was the only adverse event that correlated with CYP2C19 (*2/*2) allele (p=0.0489, OR=10; 95% CI [1.39-71.80]).

Conclusions: HTPR assessed by MEA, in patients treated with clopidogrel after coronary artery stenting was found to be an important risk factor of ischemic cerebral events. In concordance, the carriers of CYP2C19*2/*2 allele showed an increased rate of ischemic cerebral events.

Keywords: Aggregation; Antiplatelet therapy; Clopidogrel; Stroke.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Blood Platelets / drug effects*
  • Brain Ischemia / etiology*
  • Brain Ischemia / genetics
  • Clopidogrel
  • Coronary Artery Disease / surgery
  • Cytochrome P-450 CYP2C19 / genetics
  • Female
  • Humans
  • Male
  • Middle Aged
  • Percutaneous Coronary Intervention / adverse effects*
  • Platelet Aggregation / drug effects
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Platelet Function Tests
  • Polymorphism, Genetic
  • Risk Factors
  • Ticlopidine / analogs & derivatives*
  • Ticlopidine / therapeutic use

Substances

  • Platelet Aggregation Inhibitors
  • Clopidogrel
  • Cytochrome P-450 CYP2C19
  • Ticlopidine