title: Influence of CYP2C19 genetic polymorphisms on clinical outcomes of intracranial aneurysms treated with stent-assisted coiling.
abstract: OBJECTIVE
  To investigate the influence of CYP2C19 genetic polymorphisms on clinical outcomes of intracranial aneurysms treated with stent-assisted coiling.
  
  
  METHODS
  Between September 2014 and October 2015, we prospectively recruited 215 patients with intracranial aneurysms who were treated with stent-assisted coiling. CYP2C19 genotypes were determined and clopidogrel response was tested. The primary endpoints included symptomatic or silent ischemic events, and bleeding events. The secondary endpoint was clinical outcome at 3 months.
  
  
  RESULTS
  Of the 215 patients, 108 (50.2%) were classified as intermediate metabolizers (IMs, CYP2C19*1/*2, *1/*3), 76 (35.3%) as extensive metabolizers (EMs, CYP2C19*1/*1) and 31 (14.4%) as poor metabolizers (PMs, CYP2C19*2/*2, *2/*3, *3/*3). Carriers of CYP2C19 loss-of-function (LOF) alleles (*2 or *3, p=0.001), especially PMs (p=0.004), had an increased risk for clopidogrel resistance. After the procedures, cerebral ischemic events occurred in 69 patients (32.1%) and bleeding was seen in 20 patients (9.3%). In comparison with IMs and PMs, EMs had a lower risk for ischemic events (21.1% vs 37.0% and 41.9%, p=0.02 and 0.027, respectively) and a relatively higher risk for bleeding events (18.4% vs 5.6% and 0%, p=0.006 and 0.01, respectively). Based on multivariate analysis, the carriage of CYP2C19 LOF alleles (p=0.032) and clopidogrel resistance (p=0.047) were considered as predictors of cerebral ischemic events, and EMs were significantly associated with bleeding (p=0.002). Posterior circulation aneurysms (p=0.038), hemorrhagic history (p=0.001) and poor metabolic genotypes (p=0.001) could result in poor clinical outcomes (modified Rankin Scale >2).
  
  
  CONCLUSIONS
  CYP2C19 genetic polymorphisms had significant influence on the antiplatelet effect of clopidogrel, and could be considered as risk factors of ischemic or bleeding events and even clinical outcomes of patients with intracranial aneurysms treated with stent-assisted coiling.
authors.affiliation: Department of Interventional Neuroradiology, Beijing Neurosurgical Institute and Beijing Tiantan Hospital, Capital Medical University, Beijing, China.|Beijing Engineering Research Center for Interventional Neuroradiology, Beijing, China.
authors.forename: Huijian
authors.initials: H
authors.lastname: Ge
authors.affiliation: Department of Interventional Neuroradiology, Beijing Neurosurgical Institute and Beijing Tiantan Hospital, Capital Medical University, Beijing, China.|Beijing Engineering Research Center for Interventional Neuroradiology, Beijing, China.
authors.forename: Xianli
authors.initials: X
authors.lastname: Lv
authors.affiliation: Laboratory Diagnosis Center, Beijing Luhe Hospital, Capital Medical University, Beijing, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Ren
authors.affiliation: Department of Interventional Neuroradiology, Beijing Neurosurgical Institute and Beijing Tiantan Hospital, Capital Medical University, Beijing, China.|Beijing Engineering Research Center for Interventional Neuroradiology, Beijing, China.
authors.forename: Hengwei
authors.identifier: http://orcid.org/0000-0002-6830-6300
authors.initials: H
authors.lastname: Jin
authors.affiliation: Department of Interventional Neuroradiology, Beijing Neurosurgical Institute and Beijing Tiantan Hospital, Capital Medical University, Beijing, China.|Beijing Engineering Research Center for Interventional Neuroradiology, Beijing, China.
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Interventional Neuroradiology, Beijing Neurosurgical Institute and Beijing Tiantan Hospital, Capital Medical University, Beijing, China.|Beijing Engineering Research Center for Interventional Neuroradiology, Beijing, China.
authors.forename: Hongwei
authors.initials: H
authors.lastname: He
authors.affiliation: Department of Interventional Neuroradiology, Beijing Neurosurgical Institute and Beijing Tiantan Hospital, Capital Medical University, Beijing, China.|Beijing Engineering Research Center for Interventional Neuroradiology, Beijing, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Liu
authors.affiliation: Department of Interventional Neuroradiology, Beijing Neurosurgical Institute and Beijing Tiantan Hospital, Capital Medical University, Beijing, China.|Beijing Engineering Research Center for Interventional Neuroradiology, Beijing, China.
authors.forename: Youxiang
authors.initials: Y
authors.lastname: Li
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000077144:Clopidogrel; D065731:Cytochrome P-450 CYP2C19 / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D006470:Hemorrhage / Q000209:etiology / Q000235:genetics; D006801:Humans; D002532:Intracranial Aneurysm / Q000235:genetics* / Q000628:therapy*; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D011110:Polymorphism, Genetic / Q000235:genetics*; D011446:Prospective Studies; D015607:Stents / Q000009:adverse effects; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D013988:Ticlopidine
keywords: Aneurysm; Complication; Platelets; Stent