Association Between <i>CYP2B6</i> Polymorphisms and Efficacy of Clopidogrel in Minor Stroke or Transient Ischemic Attack.

Abstract

CYP2B6 (cytochrome P450 subfamily IIB polypeptide 6), encoded by the <i>CYP2B6</i> gene, is a critical enzyme involved in clopidogrel metabolism. However, the association between <i>CYP2B6</i> polymorphisms and the efficacy of clopidogrel in minor stroke or transient ischemic attack for secondary stroke prevention remains unclear. Based on CHANCE (Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events) randomized clinical trial of aspirin plus clopidogrel versus aspirin alone, we investigated the role of <i>CYP2B6</i> polymorphisms and the efficacy of clopidogrel in patients with minor stroke or transient ischemic attack in China from October 2009 to July 2012. A total of 2853 patients were successfully genotyped for <i>CYP2B6</i>-516G>T, rs3745274 and <i>CYP2B6</i>-1456 T>C, rs2054675. The primary efficacy and safety outcomes were new stroke and any bleeding within 90 days. Among the 2853 patients, 32.8% were identified as the carriers of the <i>CYP2B6</i>-516 GT/TT or -1456 TC/CC genotype. The incidences of 90-day new stroke in aspirin plus clopidogrel and aspirin alone groups were 7.1% versus 11.3% among noncarriers, respectively; and 9.7% versus 12.2% among carriers, respectively. The efficacy of aspirin plus clopidogrel versus aspirin alone was not significantly different (<i>P</i> interaction=0.29) in noncarriers (adjusted hazard ratio, 0.61 [95% CI, 0.45-0.83]) compared to carriers (adjusted hazard ratio, 0.80 [95% CI, 0.54-1.18]). The incidence (n=51) of 90-day any bleeding in aspirin plus clopidogrel and aspirin alone groups were 2.2% (21 bleeds) versus 1.9% (18 bleeds) among noncarriers (adjusted hazard ratio, 1.11 [95% CI, 0.59-2.09]) and 1.9% (9 bleeds) versus 0.7% (3 bleeds) among carriers (adjusted hazard ratio, 3.23 [95% CI, 0.86-12.12]). Similar findings were observed during the 1-year follow-up. In this post hoc analysis of the CHANCE trial, we did not observe a significant difference in the efficacy of aspirin plus clopidogrel compared with aspirin in carriers versus noncarriers of <i>CYP2B6</i>-516 GT/TT or -1456 TC/CC genotype. Our results suggest that both carriers and noncarriers suffering from a minor stroke are likely to benefit from aspirin plus clopidogrel treatment over aspirin monotherapy for secondary prevention. URL: https://www. gov; Unique identifier: NCT00979589.