Influence of CYP2C19 genetic polymorphisms on clinical outcomes of intracranial aneurysms treated with stent-assisted coiling

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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.

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