Association between CYP2C9 polymorphisms and ischemic stroke following endovascular neurointervention

• Published in: Journal of stroke and cerebrovascular diseases Vol. 29; no. 8; p. 104901
• Main Authors: Sreedharan, Subhashaan, Churilov, Leonid, Chan, Jianxiong, Todaro, Marian, Coulthard, Alan, Hocking, Jeffrey, Mahady, Kate, Mitchell, Peter, Dowling, Richard, Bush, Steven, Kwan, Patrick, Yan, Bernard
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-08-2020
• Subjects: Antiplatelet; Clopidogrel; CYP2C9; Endovascular; Ischemia; Neurointervention; Stroke; CYP2C9; Stroke; Antiplatelet; Ischemia; Endovascular; Neurointervention; Clopidogrel
• ISSN: 1052-3057; 1532-8511
• DOI: 10.1016/j.jstrokecerebrovasdis.2020.104901

Polymorphisms in the CYP2C9 gene may be associated with adverse vascular events following endovascular procedures independent of antiplatelet therapy. We aimed to investigate the impact of CYP2C9 loss-of-function polymorphisms on adverse vascular events following neurointervention.
Consecutive patients undergoing neurointervention were prospectively recruited between 2010 and 2016. Patients were genotyped for the CYP2C9*2 and *3 loss-of-function polymorphisms. On the basis of possible genetic influence on antiplatelet response, ex vivo clopidogrel response was measured using the VerifyNow® P2Y12 Assay. The primary endpoint was the 90-day incidence of adverse vascular events including ischemic stroke.
A total of 229 patients were included. The median age was 57 years (IQR: 49–64), and 158 (69.00%) were female. Eighty-one (35.37%) patients carried at least one CYP2C9 loss-of-function (LOF) allele. After adjustment for stroke risk factors, the 90-day incidence of ischemic stroke was significantly lower in the LOF group compared to the wild type group (1.23% vs 10.14%; ORadj = 0.16, 95% CI: 0.03–0.91; p = 0.04).
Our results suggest protection against ischemic stroke in carriers of CYP2C9*2 or *3 polymorphisms undergoing neurointervention. Our findings warrant further studies to investigate the mechanisms by which CYP2C9 may influence the risk of ischemic stroke.