Department of Neurology, Neurological Institute, Taipei Veterans General Hospital, No. 201, Section 2, Shih-Pai Road, Taipei, 112, Taiwan.
Department of Neurology, School of Medicine, National Yang Ming Chao Tung University, Taipei, Taiwan.
Sci Rep. 2023 May 19;13(1):8085. doi: 10.1038/s41598-023-34481-5.
Clopidogrel is the most-widely used platelet P2Y12-inhibitor for secondary-prevention of ischemic stroke. Platelet P2Y12 reactivity before and after inhibitors can be measured with blood sampling by commercialized system. We aimed to evaluate (1) whether high-on-clopidogrel platelet P2Y12 reactivity (HCPR) is associated with short-term vascular events and (2) the predictors of HCPR in acute stroke. The inclusion criterion was patients with acute stroke who received clopidogrel within 12-48 h after the onset. Platelet reactivity was assayed at baseline and after clopidogrel treatment using the VerifyNow system. The primary endpoint was recurrent ischemic events within 21 days after stroke. Among 190 patients, 32(16.9%) had recurrent ischemic stroke. Multivariate analyses showed that HCPR was significantly associated with the short-term events with an odds-ratio of 2.5 (95% CI 1.1-5.7, p = 0.027). Patients with HCPR had significantly higher frequencies of high baseline platelet P2Y12 reactivity, impaired kidney function, and carrying one or two CYP2C19 loss-of-function alleles. A poor clopidogrel response score combining these factors was developed. Ten percent of patients with score 0, 20.3% of those with score 1, 38.3% of those with score 2, and 66.7% of those with score 3 had HCPR (χ-test, p < 0.001). Multivariate analyses showed that, compared with the score-0 group, the score-2 and -3 groups had higher risks of HCPR with hazard-ratios of 5.4 (95% CI 1.5-20.3, p = 0.012) and 17.4 (95% CI 3.4-88.9, p = 0.001) for developing recurrent ischemic strokes. The study emphasized the role of HCPR in ischemic stroke. We also developed an HCPR risk score, which could be used in clinical practice or trials, potentially with more precision, to weigh the clinical benefit of a tailored antiplatelet-strategy for patients with stroke.
氯吡格雷是缺血性脑卒中二级预防中应用最广泛的血小板 P2Y12 抑制剂。可通过商业化系统采血来测量抑制剂使用前后血小板 P2Y12 的反应性。我们旨在评估：（1）高氯吡格雷血小板 P2Y12 反应性（HCPR）是否与短期血管事件相关；（2）急性脑卒中患者 HCPR 的预测因素。纳入标准为脑卒中发病后 12-48 小时内接受氯吡格雷治疗的患者。使用 VerifyNow 系统在基线和氯吡格雷治疗后测定血小板反应性。主要终点是卒中后 21 天内的复发性缺血事件。在 190 例患者中，32 例（16.9%）发生了复发性缺血性脑卒中。多变量分析显示，HCPR 与短期事件显著相关，比值比为 2.5（95%可信区间为 1.1-5.7，p=0.027）。HCPR 患者的基线血小板 P2Y12 反应性较高、肾功能受损和携带一个或两个 CYP2C19 失活等位基因的频率显著较高。开发了一种结合这些因素的氯吡格雷反应不良评分。评分 0 分的患者中 10%、评分 1 分的患者中 20.3%、评分 2 分的患者中 38.3%、评分 3 分的患者中 66.7%有 HCPR（卡方检验，p<0.001）。多变量分析显示，与评分 0 组相比，评分 2 组和 3 组发生 HCPR 的风险更高，危险比分别为 5.4（95%可信区间为 1.5-20.3，p=0.012）和 17.4（95%可信区间为 3.4-88.9，p=0.001）。该研究强调了 HCPR 在缺血性脑卒中中的作用。我们还开发了一种 HCPR 风险评分，该评分可用于临床实践或临床试验，以更精确的方式权衡为脑卒中患者制定个体化抗血小板策略的临床获益。
