| Background: Intracranial aneurysm is an abnormal embossment of arterial wall and is considered as the severe disease that harms the human health.There was a controversy referring to the therapeutic methods on intracranial aneurysm.With the development of medical material,intracranial stents have been used for the wide-necked or complicated aneurysms.However,stents could cause the intracranial thromboembolic complications that limit the application of stents.In recent years,the utilize of dual antiplatelet therapy,especially clopidogrel,decreased the risk of thromboembolic complications significantly.During the standard treatment of clopidogrel,part of patients could not achieve the excepted antiplatelet effect and were considered as the “clopidogrel resistance”.Several studies confirmed that the genetic polymorphisms,especially CYP2C19 polymorphisms,was the main factor of clopidogrel resistance.But the literature referring to intracranial aneurysms was still insufficient.Objective: This study aimed to investigate the influence of CYP2C19 genetic polymorphisms on clinical outcomes in intracranial aneurysms treated with stent-assisted coiling.Methods: Between September 2014 and October 2015,we prospectively registered patients of intracranial aneurysms who undergoing stent placement in interventional neuroradiology department of Beijing Tiantan hospital.Patients' clinical and imaging information were recorded carefully.All included patients were tested the CYP2C19 genotypes,clopidogrel response,the platelet function(by thrombelastography,TEG)on admission,pre-operation and post operation or follow-up.All patients received MR imaging,including weighted diffusion imaging,within postoperative 48 hours to identify acute ischemic stroke.The primary endpoint included symptomatic or silent ischemic events,and bleeding events.The secondary endpoint was assessed by modified Rankin Scale(m RS)at 3 months.The correlations of CYP2C19 polymorphisms,platelet function and the clinical outcomes were analyzed.Results: A total of 215 patients were prospectively recruited in our database,including 86 males(40.0%)and 129 females(60.0%).The mean age of these patients were 52.3±10.2 years old with a range of 18 to 79 years old.In our study,243 intracranial aneurysms were treated with 275 stents,including 170(69.9%)anterior circulation aneurysms and 73(30.1%)posterior circulation aneurysms.On immediate postoperative angiograms,171(79.5%)aneurysms were occluded completely;25(11.6%)were occluded near-completely and 19(8.9%)were partly occluded.Of the 215 patients,108(50.3%)were classified as intermediate metabolizers(IM,CYP2C19*1/*2,*1/*3),76(35.3%)as extensive metabolizers(EM,CYP2C19*1/*1)and 31(14.4%)as poor metabolizers(PM,CYP2C19*2/*2,*2/*3,*3/*3).Besides,68(31.6%)patients were detected to have clopidogrel resistance;cerebral ischemic events occurred in 69 patients(32.1%)and bleeding events in 20 patients(9.3%)during 3 months follow-up.Comparing with IMs and PMs,EMs had a lower risk of ischemic events(21.1% vs 37.0% and 41.9%,p=0.02 and 0.027)and a relative higher risk of bleeding events(18.4% vs 5.6% and 0%,p=0.006 and 0.01).Bases on multivariate analysis,the carriage of CYP2C19 loss of function(LOF)allele(p=0.032,OR=2.07,95%CI=1.063-4.03)and clopidogrel resistance(p=0.047,OR=0.534,95%CI=0.287-0.993)were considered as the predictors of cerebral ischemic events,and EMs were significantly associated with bleeding events(p=0.002,OR=0.205,95%CI=0.075-0.557).The patients with the posterior circulation aneurysms(p=0.038,OR=3.856,95%CI=1.076-13.822),hemorrhagic history(p=0.001,OR=0.078,95%CI=0.019-0.329)and poor metabolic genotypes(p=0.001,R=9.058,95%CI=2.366-34.682)had poor clinical outcomes(m RS>2).Conclusion: CYP2C19 genetic polymorphisms had significant influence on antiplatelet effect of clopidogrel,and could be considered as potential predictors of ischemic or bleeding events and even clinical outcomes for intracranial aneurysms treated with stent-assisted coiling. |
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