Subhashaan Sreedharan1, Leonid Churilov2, Jianxiong Chan3, Marian Todaro4, Alan Coulthard5, Jeffrey Hocking5, Kate Mahady5, Peter Mitchell6, Richard Dowling6, Steven Bush6, Patrick Kwan7, Bernard Yan8. 1. Melbourne Brain Centre, Royal Melbourne Hospital, Parkville, VIC 3050, Australia; Department of Medicine, University of Melbourne, Parkville, VIC 3050, Australia. 2. Florey Institute of Neuroscience and Mental Health, Heidelberg, VIC 3084, Australia. 3. Department of Medicine, University of Melbourne, Parkville, VIC 3050, Australia; Department of Neuroscience, CCS, Monash University, Melbourne, VIC 3004, Australia. 4. Department of Medicine, University of Melbourne, Parkville, VIC 3050, Australia; Department of Neurology, Royal Melbourne Hospital, Parkville, VIC 3050, Australia; Department of Neuroscience, CCS, Monash University, Melbourne, VIC 3004, Australia. 5. Department of Medical Imaging, Royal Brisbane and Women's Hospital, QLD 4029, Australia; Academic Discipline of Medical Imaging, University of Queensland, QLD 4072, Australia. 6. Department of Radiology, Royal Melbourne Hospital, Parkville, VIC 3050, Australia; Department of Radiology, University of Melbourne, Parkville, VIC 3050, Australia. 7. Melbourne Brain Centre, Royal Melbourne Hospital, Parkville, VIC 3050, Australia; Department of Medicine, University of Melbourne, Parkville, VIC 3050, Australia; Department of Neurology, Royal Melbourne Hospital, Parkville, VIC 3050, Australia; Department of Neuroscience, CCS, Monash University, Melbourne, VIC 3004, Australia; Department of Neurology, Alfred Health, Melbourne, VIC 3004, Australia. 8. Melbourne Brain Centre, Royal Melbourne Hospital, Parkville, VIC 3050, Australia; Department of Medicine, University of Melbourne, Parkville, VIC 3050, Australia; Department of Neurology, Royal Melbourne Hospital, Parkville, VIC 3050, Australia; Department of Radiology, Royal Melbourne Hospital, Parkville, VIC 3050, Australia. Electronic address: Bernard.Yan@mh.org.au.
Abstract
OBJECTIVE: 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. PATIENTS AND METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.
OBJECTIVE: 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. PATIENTS AND METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.