title: Variability in initial response to standard clopidogrel therapy, delayed conversion to clopidogrel hyper-response, and associated thromboembolic and hemorrhagic complications in patients undergoing endovascular treatment of unruptured cerebral aneurysms.
abstract: OBJECTIVE
  Variability in response to clopidogrel therapy is increasingly being recognized as an important factor in thromboembolic and hemorrhagic complications encountered after neurointerventional procedures. This study aims to determine the variability in response to clopidogrel therapy and associated complications in patients undergoing endovascular treatment of unruptured cerebral aneurysms.
  
  
  METHODS
  We recorded baseline patient characteristics, co-administered medications, P2Y12 reaction units (PRU) values with VerifyNow, clopidogrel dosing, and thromboembolic and hemorrhagic complications in patients undergoing endovascular treatment of unruptured cerebral aneurysms at our institution during a 19 month period.
  
  
  RESULTS
  100 patients were included in the study, 76 women and 24 men, mean age 57.3 years. 15 patients exhibited an initial clopidogrel hypo-response (PRU >240) and 21 patients an initial clopidogrel hyper-response (PRU <60). 36 patients had a follow-up VerifyNow test performed without changes to the standard 75 mg daily clopidogrel dose, which demonstrated that 59% of patients who had initially been within the target 60-240 PRU range exhibited a delayed conversion to clopidogrel hyper-response. In our cohort, a clopidogrel hypo-response was associated with a significantly increased risk of thromboembolic complications in patients undergoing cerebral aneurysm treatment with stent assistance or the pipeline embolization device (60%, p=0.003), while a clopidogrel hyper-response was associated with a significantly increased risk of major hemorrhagic complications in all patients undergoing endovascular treatment of cerebral aneurysms (11%, p=0.016).
  
  
  CONCLUSIONS
  We found wide and dynamic variability in response to clopidogrel therapy in patients undergoing endovascular treatment of unruptured cerebral aneurysms, which was significantly associated with thromboembolic and major hemorrhagic complications in our cohort.
authors.affiliation: Division of Interventional Neuroradiology, Neuroscience Institute, Abbott Northwestern Hospital, Minneapolis, Minnesota, USA.
authors.forename: Josser E
authors.initials: JE
authors.lastname: Delgado Almandoz
authors.affiliation: Division of Interventional Neuroradiology, Neuroscience Institute, Abbott Northwestern Hospital, Minneapolis, Minnesota, USA.
authors.forename: Yasha
authors.initials: Y
authors.lastname: Kadkhodayan
authors.affiliation: Division of Interventional Neuroradiology, Neuroscience Institute, Abbott Northwestern Hospital, Minneapolis, Minnesota, USA.
authors.forename: Benjamin M
authors.initials: BM
authors.lastname: Crandall
authors.affiliation: Division of Interventional Neuroradiology, Neuroscience Institute, Abbott Northwestern Hospital, Minneapolis, Minnesota, USA.
authors.forename: Jill M
authors.initials: JM
authors.lastname: Scholz
authors.affiliation: Division of Interventional Neuroradiology, Neuroscience Institute, Abbott Northwestern Hospital, Minneapolis, Minnesota, USA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Fease
authors.affiliation: Division of Interventional Neuroradiology, Neuroscience Institute, Abbott Northwestern Hospital, Minneapolis, Minnesota, USA.
authors.forename: David E
authors.initials: DE
authors.lastname: Tubman
mesh_terms: D002543:Cerebral Hemorrhage / Q000139:chemically induced / Q000209:etiology*; D000077144:Clopidogrel; D057510:Endovascular Procedures / Q000009:adverse effects*; D005260:Female; D006801:Humans; D002532:Intracranial Aneurysm / Q000150:complications / Q000601:surgery*; D020766:Intracranial Embolism / Q000139:chemically induced / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D013988:Ticlopidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine
keywords: Aneurysm; Flow Diverter; Hemorrhage; Platelets; Stroke