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

Abstract

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.

• Authors: Hongliang Wu, Huiqun Song, Lianwei Dou, Bo Gao, Yan Pan, Mei Dong, Qi Chen, Jiazhen Li, Lixiang Song, Chuanyu Liu, Bing Li, Wenzheng Chu
• Journal: BMC neurology (BMC Neurol) Vol. 20 Issue 1 Pg. 395 (Oct 29 2020) ISSN: 1471-2377 [Electronic] England
• PMID: 33121452 (Publication Type: Journal Article, Randomized Controlled Trial)

Chemical References

• Platelet Aggregation Inhibitors
• Clopidogrel
• CYP2C19 protein, human
• Cytochrome P-450 CYP2C19
• Aspirin

Topics

• 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, etiology, genetics)
• Male
• Middle Aged
• Platelet Aggregation Inhibitors (therapeutic use)
• Treatment Outcome