Effectiveness and safety of high dose clopidogrel plus aspirin in ischemic stroke patients with the single CYP2C19 loss-of-function allele: a randomized trial.
Aged
Aspirin
/ administration & dosage
Carotid Stenosis
/ complications
Clopidogrel
/ administration & dosage
Cytochrome P-450 CYP2C19
/ genetics
Dose-Response Relationship, Drug
Female
Heterozygote
Humans
Ischemic Stroke
/ drug therapy
Male
Middle Aged
Platelet Aggregation Inhibitors
/ therapeutic use
Treatment Outcome
CYP2C19
Carotid stenosis
Clopidogrel
Dual antiplatelet aggregation therapy
Intracranial stenosis
Ischaemic stroke
Journal
BMC neurology
ISSN: 1471-2377
Titre abrégé: BMC Neurol
Pays: England
ID NLM: 100968555
Informations de publication
Date de publication:
29 Oct 2020
29 Oct 2020
Historique:
received:
11
07
2020
accepted:
23
10
2020
entrez:
30
10
2020
pubmed:
31
10
2020
medline:
12
1
2021
Statut:
epublish
Résumé
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. 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. 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. 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. 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.
Sections du résumé
BACKGROUND
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
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
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
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
BACKGROUND
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.
Identifiants
pubmed: 33121452
doi: 10.1186/s12883-020-01974-z
pii: 10.1186/s12883-020-01974-z
pmc: PMC7596994
doi:
Substances chimiques
Platelet Aggregation Inhibitors
0
Clopidogrel
A74586SNO7
CYP2C19 protein, human
EC 1.14.14.1
Cytochrome P-450 CYP2C19
EC 1.14.14.1
Aspirin
R16CO5Y76E
Types de publication
Journal Article
Randomized Controlled Trial
Langues
eng
Sous-ensembles de citation
IM
Pagination
395Subventions
Organisme : Department of Health of Shandong Province
ID : 2017WS168
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