Wang Yicong, Pan Yuesong, Wang Xuan, Gao Ying, Chen Weiqi, Johnston S Claiborne, Bath Philip M, Amarenco Pierre, Gao Cong, Wang Yongjun, Liao Xiaoling, Wang Yilong
Department of Neurology Beijing Tiantan Hospital, Capital Medical University Beijing China.
China National Clinical Research Center for Neurological Diseases Beijing China.
J Am Heart Assoc. 2025 Jul 15;14(14):e040492. doi: 10.1161/JAHA.124.040492. Epub 2025 Jul 14.
Inflammation is an important mechanism in ischemic stroke and high-risk transient ischemic attack, but clinical inflammatory markers on antiplatelet therapy remain to be studied. This study was designed compare the neutrophil count (NC) on the efficacy and safety of clopidogrel-aspirin with that of aspirin in patients with ischemic stroke or high-risk transient ischemic attack caused by intracranial or extracranial atherosclerosis.
The INSPIRES (Intensive Statin and Antiplatelet Therapy for High-Risk Intracranial or Extracranial Atherosclerosis) study was a post hoc analysis of the multicenter, randomized, double-blind, placebo-controlled, 2-by-2 factorial trial. The primary efficacy and safety outcomes were 90-day stroke and moderate-to-severe bleeding. The differences in the efficacy outcome were calculated with cox proportional hazards model and the generalized linear model as well as logistic regression.
The study included 5929 patients of median age 65 years (interquartile range, 57-71 years), 3800 (64.09%) of whom were men; 1983 (33.45%) had a low NC (≤3.65×10/L), 1973 (33.28%) had an intermediate NC (3.65<NC≤4.97×10/L), and 1973 (33.28%) had a high NC (>4.97×10/L). Patients with ischemic stroke or transient ischemic attack with a higher NC benefited more from clopidogrel-aspirin than from aspirin alone. There was no significant difference in the primary safety outcome of moderate-to-severe bleeding according to antiplatelet therapy or NC.
The post hoc analysis suggested patients with a higher NC obtained greater benefit from clopidogrel-aspirin than from aspirin without an increase in bleeding risk. The findings may serve as a reference indicator for future anti-inflammatory therapy. However, further research is needed to explore the mechanism.
炎症是缺血性卒中和高危短暂性脑缺血发作的重要机制，但抗血小板治疗中的临床炎症标志物仍有待研究。本研究旨在比较颅内或颅外动脉粥样硬化所致缺血性卒中或高危短暂性脑缺血发作患者中，氯吡格雷联合阿司匹林与单用阿司匹林治疗时的中性粒细胞计数（NC）对疗效和安全性的影响。
INSPIRES（强化他汀与抗血小板治疗用于高危颅内或颅外动脉粥样硬化）研究是一项对多中心、随机、双盲、安慰剂对照的2×2析因试验的事后分析。主要疗效和安全性结局为90天卒中及中至重度出血。疗效结局的差异采用Cox比例风险模型、广义线性模型以及逻辑回归进行计算。
该研究纳入了5929例年龄中位数为65岁（四分位间距为57 - 71岁）的患者，其中3800例（64.09%）为男性；1983例（33.45%）NC较低（≤3.65×10⁹/L），1973例（33.28%）NC中等（3.65＜NC≤4.97×10⁹/L），1973例（33.28%）NC较高（＞4.97×10⁹/L）。缺血性卒中或短暂性脑缺血发作且NC较高的患者，氯吡格雷联合阿司匹林治疗比单用阿司匹林获益更多。根据抗血小板治疗或NC，中至重度出血的主要安全性结局无显著差异。
事后分析表明，NC较高的患者使用氯吡格雷联合阿司匹林比单用阿司匹林获益更大，且出血风险未增加。这些发现可为未来的抗炎治疗提供参考指标。然而，需要进一步研究来探索其机制。
