This article requires a subscription to view the full text. If you have a subscription you may use the login form below to view the article. Access to this article can also be purchased.
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.
Clinicaltrials.gov Identifier NCT00979589.
Glossary
- CHANCE=
- Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events;
- CI=
- confidence interval;
- HR=
- hazard ratio;
- LOF=
- loss of function;
- PAR-1=
- protease-activated receptor-1;
- SNP=
- single nucleotide polymorphism
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
↵* These authors contributed equally to this work.
Editorial, page 10
- Received February 25, 2020.
- Accepted in final form August 6, 2020.
- © 2020 American Academy of Neurology
AAN Members
We have changed the login procedure to improve access between AAN.com and the Neurology journals. If you are experiencing issues, please log out of AAN.com and clear history and cookies. (For instructions by browser, please click the instruction pages below). After clearing, choose preferred Journal and select login for AAN Members. You will be redirected to a login page where you can log in with your AAN ID number and password. When you are returned to the Journal, your name should appear at the top right of the page.
AAN Non-Member Subscribers
Purchase access
Letters: Rapid online correspondence
REQUIREMENTS
You must ensure that your Disclosures have been updated within the previous six months. Please go to our Submission Site to add or update your Disclosure information.
Your co-authors must send a completed Publishing Agreement Form to Neurology Staff (not necessary for the lead/corresponding author as the form below will suffice) before you upload your comment.
If you are responding to a comment that was written about an article you originally authored:
You (and co-authors) do not need to fill out forms or check disclosures as author forms are still valid
and apply to letter.
Submission specifications:
- Submissions must be < 200 words with < 5 references. Reference 1 must be the article on which you are commenting.
- Submissions should not have more than 5 authors. (Exception: original author replies can include all original authors of the article)
- Submit only on articles published within 6 months of issue date.
- Do not be redundant. Read any comments already posted on the article prior to submission.
- Submitted comments are subject to editing and editor review prior to posting.
