F2R polymorphisms and clopidogrel efficacy and safety in patients with minor stroke or TIA: supplemental figures and tables

Objective: To investigate the association between protease-activated receptors-1 (PAR-1) gene F2R polymorphisms and efficacy of clopidogrel for minor stroke or transient ischemic attack (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=1461) or aspirin alone (n=1463). 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, 1479(50.6%) were AT heterozygotes and 586(20.0%) were TT homozygotes for F2R IVSn -14 polymorphisms; 1716 (58.7%) were carriers of at least one 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 F2R IVSn -14 T allele had a lower rate of recurrent stroke than those who were not.

Clinicaltrials.gov Identifier: NCT00979589.

Methods
Supplemental Data corresponding to research paper 'F2R Polymorphisms and Clopidogrel Efficacy and Safety in Patients with Minor Stroke or TIA'

It contains supplemental figures and supplemental tables for this paper.