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

<p><b>Objective</b>: To investigate the association between protease-activated receptors-1 (PAR-1) gene<i> F2R</i> polymorphisms and efficacy of clopidogrel for minor stroke or transient ischemic attack (TIA).</p> <p><b>Methods</b>: Three single-nucleotide polymorphisms (<i>CYP2C19*2</i> [681G&gt;A, rs4244285], <i>CYP2C19</i>*<i>3</i> [636G&gt;A, rs4986893] and <i>F2R</i> [IVSn-14 A/T, rs168753] were genotyped among<span> 2,924 patients randomized to clopidogrel plus aspirin (n=1461) or aspirin alone (n=1463). </span>The primary efficacy outcome was new stroke (ischemic or hemorrhagic) and the safety outcome was any bleeding.</p> <p><b>Results: </b>Overall, 859(29.4%) were AA homozygotes, 1479(50.6%) were AT heterozygotes and 586(20.0%) were TT homozygotes for <i>F2R</i> IVSn -14 polymorphisms; 1716 (58.7%) were carriers of at least one<i> CYP2C19</i> 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% <i>vs.</i> 11.3%; hazard ratio [HR], 0.63; 95% confidence interval [CI], 0.44-0.89) and TT genotype (5.8% <i>vs.</i> 11.6%; HR, 0.46; 95% CI, 0.25-0.82) but not in carriers of the AA genotype (10.8% <i>vs.</i> 11.6%; HR, 0.95; 95% CI, 0.63-1.44) (p=0.03 for interaction). The association between <i>F2R</i> IVSn -14 A/T polymorphism and clopidogrel response was present regardless of the carrier status of the <i>CYP2C19</i> loss-of-function alleles. The<i> F2R</i> IVSn -14 genotypes were not associated with the risk of any bleeding for clopidogrel-aspirin treatment (P=0.66 for interaction).</p> <p><span><b>Conclusions:</b><b> </b></span>Among patients with minor ischemic stroke or TIA who were receiving clopidogrel and aspirin, those carrying <i>F2R</i> IVSn -14 T allele had a lower rate of recurrent stroke than those who were not.</p> <p><span><b>Clinicaltrials.gov Identifier:</b></span> NCT00979589.</p>