F2R Polymorphisms and Clopidogrel Efficacy and Safety in Patients With Minor Stroke or TIA.

Abstract

OBJECTIVE:

To investigate the association between protease-activated receptor-1 (PAR-1) gene F2R polymorphisms and efficacy of clopidogrel for minor stroke or TIA.

METHODS:

Three single nucleotide polymorphisms (CYP2C19*2 [681G>A, rs4244285], CYP2C19*3 [636G>A, rs4986893], and F2R [IVSn-14 A/T, rs168753]) were genotyped among 2,924 patients randomized to clopidogrel plus aspirin (n = 1,461) or aspirin alone (n = 1,463). The primary efficacy outcome was new stroke (ischemic or hemorrhagic) and the safety outcome was any bleeding.

RESULTS:

Overall, 859 (29.4%) were AA homozygotes, 1,479 (50.6%) were AT heterozygotes, and 586 (20.0%) were TT homozygotes for F2R IVSn-14 polymorphisms; 1,716 (58.7%) were carriers of at least 1 CYP2C19 loss-of-function allele (*2 or *3). Compared with aspirin alone, patients with clopidogrel-aspirin treatment had a low risk of new stroke in patients with AT genotype (7.6% vs 11.3%; hazard ratio [HR], 0.63; 95% confidence interval [CI], 0.44-0.89) and TT genotype (5.8% vs 11.6%; HR, 0.46; 95% CI, 0.25-0.82) but not in carriers of the AA genotype (10.8% vs 11.6%; HR, 0.95; 95% CI, 0.63-1.44) (p = 0.03 for interaction). The association between F2R IVSn-14 A/T polymorphism and clopidogrel response was present regardless of the carrier status of the CYP2C19 loss-of-function alleles. The F2R IVSn-14 genotypes were not associated with the risk of any bleeding for clopidogrel-aspirin treatment (p = 0.66 for interaction).

CONCLUSIONS:

Among patients with minor ischemic stroke or TIA who were receiving clopidogrel and aspirin, those carrying the F2R IVSn-14 T allele had a lower rate of recurrent stroke than those who were not.

CLINICALTRIALSGOV IDENTIFIER:

NCT00979589.

• Authors: Yuesong Pan, Runqi Wangqin, Hao Li, Yilong Wang, Xia Meng, S Claiborne Johnston, Tabassome Simon, Jinxi Lin, Xingquan Zhao, Liping Liu, David Wang, Yongjun Wang
• Journal: Neurology (Neurology) Vol. 96 Issue 1 Pg. e1-e9 (01 05 2021) ISSN: 1526-632X [Electronic] United States
• PMID: 33093222 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 American Academy of Neurology.

Chemical References

• Platelet Aggregation Inhibitors
• Receptor, PAR-1
• Clopidogrel

Topics

• Aged
• Clopidogrel (therapeutic use)
• Double-Blind Method
• Female
• Genotype
• Humans
• Ischemic Attack, Transient (drug therapy, genetics)
• Male
• Middle Aged
• Platelet Aggregation Inhibitors (therapeutic use)
• Polymorphism, Single Nucleotide
• Receptor, PAR-1 (genetics)
• Recurrence
• Stroke (drug therapy, genetics)
• Treatment Outcome