Key result
Compared to extensive metabolizers, patients with CYP2C19 poor metabolizer genotypes had a higher risk of ischemic events (41.9% vs 21.1%, p=0.027) and a lower risk of bleeding (0% vs 18.4%, p=0.01).
Why the study?
Does CYP2C19 genetic polymorphism status predict ischemic and bleeding events in patients with intracranial aneurysms treated with stent-assisted coiling on clopidogrel?
Cohort (n=215)
Does CYP2C19 genetic polymorphism status predict ischemic and bleeding events in patients with intracranial aneurysms treated with stent-assisted coiling on clopidogrel?
Absolute Event Rate: 41.9% vs 21.1%
p-value: p=0.027
CYP2C19 genetic polymorphisms significantly influence clopidogrel response and predict the risk of ischemic and bleeding events in patients undergoing stent-assisted coiling for intracranial aneurysms.
CYP2C19 genotyping should not yet guide clopidogrel therapy in aneurysm stenting; leaves open need for randomized confirmation of ischemic risk.
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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Ge et al. (2016) conducted a cohort in intracranial aneurysms (n=215). CYP2C19 poor metabolizer genotype vs. CYP2C19 extensive metabolizer genotype was evaluated on symptomatic or silent ischemic events (p=0.027). Compared to extensive metabolizers, patients with CYP2C19 poor metabolizer genotypes had a higher risk of ischemic events (41.9% vs 21.1%, p=0.027) and a lower risk of bleeding (0% vs 18.4%, p=0.01).
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