急性非心源性缺血性卒中静脉溶栓后早期抗血小板治疗：系统评价与荟萃分析。
完整摘要 · 中文译文
背景：静脉溶栓（IVT）是急性缺血性卒中管理的基石；然而，因再闭塞导致的早期神经功能恶化仍是一个问题，尤其是在以富含血小板血栓为主非心源性卒中中。在该特定人群中，静脉溶栓后24小时内启动早期抗血小板治疗（APT）的安全性和有效性仍存在争议。本荟萃分析评估了关于早期APT与标准延迟APT的现有证据，特别关注所用抗血小板药物的类型。 方法：我们系统检索了PubMed、Embase和Cochrane图书馆中2021年1月至2026年3月发表的研究，并于2026年5月15日进行了补充检索，评估非心源性缺血性卒中中早期APT（静脉溶栓后≤24小时）与标准APT（>24小时）的比较。主要疗效结局为良好功能结局（90天时改良Rankin量表评分0-1）。主要安全性结局为症状性颅内出血（sICH）。采用随机效应模型计算合并比值比（OR）及95%置信区间（CI）。预先设定的仅纳入随机对照试验（RCT）的分析作为主要分析策略，观察性研究作为支持性证据纳入。 结果：共四项研究、1，394例患者纳入定量合成。在两项RCT（ASSET-IT和INSTANT，n = 1，191）中，与标准APT相比，早期替罗非班与显著更高的良好功能结局几率相关（OR 1.78，95% CI 1.38-2.30，p < 0.001，I 2 = 42%）。W 我们未检测到症状性颅内出血（sICH）的统计学显著增加（OR 1.19，95% CI 0.64-2.21，p = 0.59，I 2 = 0%）或90天死亡率的统计学显著增加（OR 0.84，95% CI 0.61-1.16，p = 0.29，I 2 = 0%）。纳入观察性研究的联合分析得出一致结果（良好结局：OR 1.72，95% CI 1.38-2.15；sICH：OR 1.25，95% CI 0.71-2.18；死亡率：OR 0.86，95% CI 0.64-1.16）。亚组分析提示，基于替罗非班的方案（OR 1.81）在数值上优于阿司匹林（OR 1.35），尽管交互作用无统计学显著性（p = 0.11）。证据基础主要涉及替罗非班，仅有一项小型研究评估了阿司匹林。 结论：在急性非心源性缺血性卒中患者中，静脉溶栓后24小时内早期给予替罗非班可显著改善功能结局。我们未检测到症状性颅内出血或死亡率的统计学显著增加。然而，置信区间不能排除sICH风险具有临床意义的增加，且出血事件数量较少限制了这些安全性估计的精确性。阿司匹林及其他抗血小板药物的证据仍非常有限，需要进一步研究。这些发现支持重新考虑当前指南对特定患者的限制，尤其是关于基于替罗非班的方案。有必要开展采用标准化方案的大规模随机对照试验，以确定最佳时机、药物选择、剂量和患者选择标准。
完整摘要 · 英文原文
BACKGROUND: Intravenous thrombolysis (IVT) is a cornerstone of acute ischemic stroke management; however, early neurological deterioration due to reocclusion remains a concern, particularly in non-cardiogenic stroke where platelet-rich thrombi predominate. The safety and efficacy of early antiplatelet therapy (APT) initiated within 24 h after IVT in this specific population remain controversial. This meta-analysis evaluates the available evidence on early APT versus standard delayed APT, with particular attention to the type of antiplatelet agent used. METHODS: We systematically searched PubMed, Embase, and the Cochrane Library for studies published between January 2021 and March 2026, with a supplementary search conducted on May 15, 2026, evaluating early APT (≤24 h after IVT) versus standard APT (>24 h) in non-cardiogenic ischemic stroke. The primary efficacy outcome was favorable functional outcome (modified Rankin Scale score 0-1 at 90 days). The primary safety outcome was symptomatic intracranial hemorrhage (sICH). Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using random-effects models. Pre-specified RCT-only analyses were conducted as the primary analytic strategy, with observational studies included as supportive evidence. RESULTS: Four studies comprising 1,394 patients were included in the quantitative synthesis. In the two RCTs (ASSET-IT and INSTANT, n = 1,191), early tirofiban was associated with significantly higher odds of favorable functional outcome compared with standard APT (OR 1.78, 95% CI 1.38-2.30, p < 0.001, I 2 = 42%). We did not detect a statistically significant increase in sICH (OR 1.19, 95% CI 0.64-2.21, p = 0.59, I 2 = 0%) or 90-day mortality (OR 0.84, 95% CI 0.61-1.16, p = 0.29, I 2 = 0%). The combined analysis including observational studies yielded consistent results (favorable outcome: OR 1.72, 95% CI 1.38-2.15; sICH: OR 1.25, 95% CI 0.71-2.18; mortality: OR 0.86, 95% CI 0.64-1.16). Subgroup analysis suggested numerically greater efficacy with tirofiban-based regimens (OR 1.81) compared with aspirin (OR 1.35), though the interaction was not statistically significant (p = 0.11). The evidence base predominantly concerns tirofiban, with only one small study evaluating aspirin. CONCLUSION: In patients with acute non-cardiogenic ischemic stroke, early tirofiban administration within 24 h after intravenous thrombolysis significantly improves functional outcomes. We did not detect a statistically significant increase in symptomatic intracranial hemorrhage or mortality. However, the confidence intervals do not exclude a clinically meaningful increase in sICH risk, and the small number of hemorrhagic events limits the precision of these safety estimates. The evidence for aspirin and other antiplatelet agents remains very limited and requires further investigation. These findings support reconsideration of current guideline restrictions for selected patients, particularly regarding tirofiban-based regimens. Large-scale randomized controlled trials with standardized protocols are warranted to establish optimal timing, agent selection, dosing, and patient selection criteria.