Effectiveness and safety of high dose clopidogrel plus aspirin in ischemic stroke patients with the single CYP2C19 loss-of-function allele: a randomized trial

Autor:	Mei Dong, Huiqun Song, Yan Pan, Bing Li, Bo Gao, Qi Chen, Jiazhen Li, Chuanyu Liu, Wenzheng Chu, Hongliang Wu, Lianwei Dou, Lixiang Song
Jazyk:	angličtina
Rok vydání:	2020
Předmět:	Male medicine.medical_specialty Heterozygote CYP2C19 Transient ischaemic attacks lcsh:RC346-429 Cerebral artery stenosis Internal medicine Diabetes mellitus Carotid stenosis Medicine Humans cardiovascular diseases Ischaemic stroke lcsh:Neurology. Diseases of the nervous system Aged Ischemic Stroke Aspirin Dose-Response Relationship Drug business.industry Hazard ratio General Medicine Middle Aged medicine.disease Clopidogrel Cytochrome P-450 CYP2C19 Stenosis Dual antiplatelet aggregation therapy Treatment Outcome Cardiology Female Neurology (clinical) Intracranial stenosis business Platelet Aggregation Inhibitors medicine.drug Research Article
Zdroj:	BMC Neurology, Vol 20, Iss 1, Pp 1-8 (2020) BMC Neurology
ISSN:	1471-2377
DOI:	10.1186/s12883-020-01974-z
Popis:	Background Dual antiplatelet aggregation therapy leads to better outcomes in patients with carotid artery stenosis, intracranial artery stenosis, minor strokes, or transient ischaemic attacks. However, carriers of the CYP2C19 loss-of-function allele may not experience the desired effects. We attempted to increase the clopidogrel dose to determine whether it would improve the outcomes of stroke patients who carry a single loss-of-function allele. Methods We recruited 131 patients with minor ischaemic stroke, within less than 7 days of stroke onset and a CYP2C19 loss-of-function allele, who had moderate-to-severe cerebral artery stenosis. Patients were divided into the high dose group (clopidogrel 150 mg per day + aspirin 100 mg per day over 21 days.) and a normal dose group (clopidogrel 75 mg per day + aspirin 100 mg per day over 21 days). The reported outcomes included any vascular or major bleeding events as the primary and safety endpoints, respectively. Results One and six vascular events occurred in the high dose and normal dose groups during the 3-months follow-up period, respectively. However, no significant difference was found between the two groups when adjusted for history of diabetes (hazard ratio, 5482; 95% confidence interval, 0.660 to 45.543; P = 0.115). No major bleeding events occurred. Conclusions In patients with ischaemic stroke who had a single CYP2C19 loss-of-function allele and moderate to severe cerebral stenosis, fewer vascular events occurred within 3 months with high dose of clopidogrel and aspirin than with normal dose of clopidogrel and aspirin. However, the difference between the two groups was not significant. Trial registration Clinical study of clopidogrel in the treatment of patients with symptomatic moderate to severe cerebral artery stenosis with intermediate metabolites of CYP2C19, URL: http://www.chictr.org.cn/. Unique identifier: ChiCTR1800017411, 07/28/2018
Databáze:	OpenAIRE
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