title: Association between high on-treatment platelet reactivity and occurrence of cerebral ischemic events in patients undergoing percutaneous coronary intervention.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
authors.affiliation: 1st Department of Cardiology, Poznan University of Medical Sciences, Poland. Electronic address: komosa.ania@gmail.com.
authors.forename: A
authors.initials: A
authors.lastname: Komosa
authors.affiliation: Department of Cardiology, Medical University of Vienna, Austria.
authors.forename: J M
authors.initials: JM
authors.lastname: Siller-Matula
authors.affiliation: 1st Department of Cardiology, Poznan University of Medical Sciences, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Lesiak
authors.affiliation: Department of Computer Science and Statistics, Poznan University of Medical Sciences, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Michalak
authors.affiliation: 1st Department of Clinical Pharmacology, Poznan University of Medical Sciences, Poland.
authors.forename: J
authors.initials: J
authors.lastname: Kowal
authors.affiliation: 1st Department of Cardiology, Poznan University of Medical Sciences, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Mączyński
authors.affiliation: 1st Department of Cardiology, Poznan University of Medical Sciences, Poland.
authors.forename: A
authors.initials: A
authors.lastname: Siniawski
authors.affiliation: 1st Department of Cardiology, Poznan University of Medical Sciences, Poland.
authors.forename: T
authors.initials: T
authors.lastname: Mularek-Kubzdela
authors.affiliation: Pathology Department Greater Poland Cancer Centre, Poznan, Poland.
authors.forename: S
authors.initials: S
authors.lastname: Wiśniewski
authors.affiliation: 1st Department of Cardiology, Poznan University of Medical Sciences, Poland.
authors.forename: S
authors.initials: S
authors.lastname: Grajek
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001792:Blood Platelets / Q000187:drug effects*; D002545:Brain Ischemia / Q000209:etiology* / Q000235:genetics; D000077144:Clopidogrel; D003324:Coronary Artery Disease / Q000601:surgery; D065731:Cytochrome P-450 CYP2C19 / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D062645:Percutaneous Coronary Intervention / Q000009:adverse effects*; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D010979:Platelet Function Tests; D011110:Polymorphism, Genetic; D012307:Risk Factors; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D065731:Cytochrome P-450 CYP2C19; D013988:Ticlopidine
keywords: Aggregation; Antiplatelet therapy; Clopidogrel; Stroke