替格瑞洛-阿司匹林联合溶栓治疗中度缺血性卒中:按梗死模式的TAPIS亚组分析
这项TAPIS试验亚组分析纳入1307例接受静脉溶栓的中度非心源性缺血性卒中患者,按DWI梗死模式分为多发急性梗死(MAIs,31.3%)和非MAIs(68.7%)。MAIs患者预后较非MAIs更差,90天良好功能结局比例分别为58.9%和69.2%。替格瑞洛-阿司匹林在MAIs亚组中与更高的良好结局率相关(64.4%对53.4%),而非MAIs亚组未见显著获益。
要点
- 多发急性梗死(MAIs)患者溶栓后预后较非MAIs更差
- 替格瑞洛-阿司匹林在MAIs亚组中良好结局率更高(64.4%对53.4%)
- 非MAIs亚组中替格瑞洛-阿司匹林未显示显著获益
核心结论
- 在溶栓治疗的中度非心源性卒中患者中,多发急性梗死(MAIs)与更差的功能结局相关。
- 替格瑞洛-阿司匹林在MAIs亚组中显示方向一致的获益,但交互作用未达常规统计学显著性。
研究设计与样本
- 这是TAPIS试验的亚组分析,TAPIS是一项60中心、随机、双盲试验,在中国开展。
- 纳入年龄18至80岁、NIHSS评分4至10分的非心源性卒中患者,发病4.5小时内接受静脉溶栓,6小时内随机分配至替格瑞洛-阿司匹林或安慰剂。
- DWI梗死模式由中心判定为多发急性梗死(MAIs,≥2个病灶)或非MAIs(单一梗死或DWI阴性)。
- 亚组分析纳入1307例患者,占全分析集的94.6%;中位年龄65.5岁,71.2%为男性,中位NIHSS评分6.0。
主要发现
- 409例(31.3%)患者为MAIs,898例(68.7%)为非MAIs,其中非MAIs中20.8%为DWI阴性,79.2%为单一梗死。
- MAIs患者良好结局率低于非MAIs(58.9%对69.2%;校正风险比0.92,95%CI 0.84至1.00)。
- MAIs亚组中替格瑞洛-阿司匹林组良好结局率为64.4%,安慰剂组为53.4%(风险比1.21,95%CI 1.02至1.42)。
- 非MAIs亚组中替格瑞洛-阿司匹林组良好结局率为71.2%,安慰剂组为67.1%(风险比1.06,95%CI 0.97至1.16)。
- 主要结局的治疗-模式交互作用P值为0.18;早期神经功能改善的交互作用P值为0.02;校正补救性替罗非班使用后主要结局交互作用P值为0.04。
关键数值与推荐
- 主要疗效结局为90天改良Rankin量表评分0至1分;安全性结局为症状性颅内出血。
- 症状性颅内出血发生率:MAIs中替格瑞洛-阿司匹林组1/205(0.5%),安慰剂组2/204(1.0%);非MAIs中两组各为1/448(0.2%)和1/450(0.2%)。
- MAIs定义为DWI上≥2个急性梗死病灶;非MAIs定义为单一梗死或DWI阴性。
临床怎么用
- 对于接受静脉溶栓的中度非心源性卒中患者,DWI显示多发急性梗死提示预后较差。
- MAIs患者中早期加用替格瑞洛-阿司匹林可能带来功能结局获益,但需注意交互作用未达稳健统计学显著性。
- 非MAIs患者中加用替格瑞洛-阿司匹林未显示显著获益,临床决策需权衡出血风险。
局限性
- 亚组分析中主要结局的治疗-模式交互作用P值为0.18,未达常规统计学显著性
- 仅在校正补救性替罗非班使用后交互作用才达到名义显著(P=0.04)
- 亚组事件数较少,尤其是症状性颅内出血事件罕见
以上解读依据论文摘要(全文未开放获取或许可不允许翻译转载)。
原文
Stroke, Volume 57, Issue 10, Page 2958-2970, October 1, 2026. BACKGROUND:Whether diffusion‑weighted imaging infarction patterns influence the efficacy and safety of early oral ticagrelor‑aspirin with intravenous thrombolysis in moderate acute ischemic stroke is uncertain. We assessed treatment effects by infarction pattern in this thrombolysis setting.METHODS:This was a subgroup analysis of the TAPIS trial (Ticagrelor With Aspirin Dual Antiplatelet Therapy Combined With Intravenous Thrombolysis in Patients With Ischemic Stroke), a 60-center, randomized, double‑blind trial in China. Patients aged 18 to 80 years with noncardioembolic stroke (National Institutes of Health Stroke Scale score 4–10) who received intravenous thrombolysis within 4.5 hours of onset were randomized within 6 hours to ticagrelor‑aspirin or placebo. Diffusion‑weighted imaging patterns were centrally adjudicated as multiple acute infarcts (MAIs; ≥2 lesions) or non‑MAIs (single infarction or diffusion‑weighted imaging–negative). The primary efficacy outcome was modified Rankin Scale score of 0 to 1 at 90 days; safety outcome was symptomatic intracranial hemorrhage. Treatment‑by‑pattern interaction was assessed.RESULTS:Among 1307 patients (94.6% of full analysis set; median age, 65.5 years; 71.2% men; median National Institutes of Health Stroke Scale score, 6.0), 409 (31.3%) had MAIs and 898 (68.7%) non‑MAIs (20.8% diffusion‑weighted imaging–negative, 79.2% single infarction). MAIs were associated with poorer prognosis than non‑MAIs (excellent outcome: 58.9% versus 69.2%; adjusted risk ratio, 0.92 [95% CI, 0.84–1.00]). Ticagrelor‑aspirin was associated with a higher likelihood of excellent outcome versus placebo in MAIs (64.4% versus 53.4%; risk ratio, 1.21 [95% CI, 1.02–1.42]), whereas no significant benefit was observed in non‑MAIs (71.2% versus 67.1%; risk ratio, 1.06 [95% CI, 0.97–1.16];Pinteraction=0.18). Early neurological improvement showed significant heterogeneity by infarction pattern (Pinteraction=0.02); the treatment‑by‑pattern interaction for the primary outcome was nominally significant after adjusting for rescue tirofiban use (P=0.04). Symptomatic intracranial hemorrhage occurred in MAIs: 1 of 205 (0.5%) versus 2 of 204 (1.0%); non‑MAIs: 1 of 448 (0.2%) versus 1 of 450 (0.2%).CONCLUSIONS:In thrombolyzed patients with moderate noncardioembolic stroke, MAIs were associated with poorer functional outcomes. Early ticagrelor‑aspirin showed directionally consistent benefits witho
引用
- Stroke:Ticagrelor-Aspirin With Thrombolysis by Infarct Patterns in Moderate Ischemic Stroke: TAPIS Subgroup Analysis
供执业医师工作参考,不替代临床判断;数值与分级以指南原文为准。