- Study examines CYP2C19 polymorphisms in patients undergoing stent-assisted coiling for intracranial aneurysms
- LoF alleles associated with clopidogrel metabolism, ischemic/bleeding risk, and outcomes
Carriage of CYP2C19 loss-of-function (LoF) alleles influences the antiplatelet effect of clopidogral in a clinically significant manner among patients undergoing stent-assisted coiling for intracranial aneurysms, according to research published online September 15, 2016, in the Journal of NeuroInterventional Surgery.
Youxiang Li, MD, of BeijingTiantan Hospital, Capital Medical University (Beijing, China), and colleagues prospectively recruited 215 patients with intracranial aneurysms treated with stent-assisted coiling between September 2014 and October 2015. For these patients, the researchers determined CYP2C19 genotype and tested clopidogrel response.
“The response to clopidogrel varies widely among individuals,” write the authors. “Different responses to clopidogrel may be related to CYP2C19 genetic polymorphisms.”
The investigators used a thromboelastography (TEG) hemostasis system (Haemoscope Corporation, Niles, Illinois, USA) to test levels of platelet inhibition. “Recently, TEG has been widely used for the assessment of platelet function,” they note. “Unlike other specific platelet function tests, TEG focuses on platelet contribution to clot strength, rather than platelet activation and aggregation, and could be used to monitor coagulation disorder[s].”
Overall, 108 patients (50.2%) were classified as intermediate clopidogrel metabolizers (*1/*2), 76 (35.3%) as extensive metabolizers (*1/*1), and 31 (14.4%) as poor metabolizers (*2/*2). There was an increased risk of clopidogral resistance among carriers of CYP2C19 LoF alleles (P = .001), especially for poor metabolizers (P = .004)
After the procedures, cerebral ischemic events occurred in 69 patients (32.1%) and bleeding in 20 (9.3%). Extensive metabolizers of clopidogrel had a lower risk of ischemic events than intermediate (P = .02) and poor metabolizers (P = .027). They also had a relatively higher risk of bleeding events (P = .006 and P = .01, respectively, table 1).
Multivariate analysis revealed that being a carrier of CYP2C19 LoF alleles (OR 2.07; 95% CI 1.06-4.03) and clopidogrel resistance (OR 0.53; 95% CI 0.29-0.99) were both predictors of cerebral ischemic event risk. Posterior circulation aneurysms (OR 3.86; 95% CI 1.08-13.82) and being a poor metabolizer (OR 9.06; 95% CI 2.37-34.68) were linked with higher risk of poor clinical outcome, defined as an mRS score > 2. Conversely, hemorrhagic history (OR 0.08; 95% CI 0.02-0.33) was associated with lower risk of poor outcome.
Also, on univariate analysis, being an extensive metabolizer was tied to lower risk of bleeding (OR 0.205; 95% CI 0.075-0.557).
“The importance of testing CYP2C19 genetic polymorphisms and platelet function should be considered to predict clinical outcomes in patients with intracranial aneurysms treated with stents and clopidogrel,” concluded the authors. “Further research is needed to focus on individualized and optimized therapeutic regimens of antiplatelet drugs.”
Ge H, Lv X, Ren H, et al. Influence of CYP2C19 genetic polymorphisms on clinical outcomes of intracranial aneurysms treated with stent-assisted coiling. J NeuroInterv Surg. 2016;Epub ahead of print.
Dr. Li reports no relevant conflicts of interest.