From the Department of Medicine and Neurology (N.Y., V.Y., L.C., B.C.V.C., H.Z., G.A.D., S.M.D.), Melbourne Brain Centre @ The Royal Melbourne Hospital, University of Melbourne; Population Health and Immunity Division (N.Y.), The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia; Division of Neurology (V.Y.), Department of Medicine, The Ottawa Hospital and Ottawa Hospital Research Institute, University of Ottawa, Ontario, Canada; Melbourne Medical School (L.C.), University of Melbourne, Parkville, Australia; Department of Neurology (A.M., D.S.), Helsinki University Hospital, Finland; Department of Neurology (T.W.), Christchurch Hospital, New Zealand; Stroke Centre and Department of Neurology (J.-S.J.), National Taiwan University Hospital, Taipei; Stroke Trials Unit (L.J.W., Z.K.L., P.M.B., N.S.), Mental Health & Clinical Neuroscience, University of Nottingham, United Kingdom; Department of Neurology (C.O.), Bispebjerg and Frederiksberg Hospital, University Hospital of Copenhagen, Denmark; Department of Medicine (Z.K.L.), Faculty of Medicine, National University of Malaysia, Kuala Lumpur; Department of Neurology (H.-Q.G., X.N., J.L., L.L.), Beijing Tiantan Hospital, Capital Medical University; China National Clinical Research Centre for Neurological Diseases (H.-Q.G., X.N., J.L., L.L.), Beijing; and Department of Neurology (H.H.M.), Monash Medical Centre, School of Clinical Sciences, Monash University, Melbourne, Australia.
Neurology. 2024 Dec 24;103(12):e210104. doi: 10.1212/WNL.0000000000210104. Epub 2024 Nov 25.
The antifibrinolytic agent tranexamic acid has been tested in intracerebral hemorrhage trials with overall neutral results. Ongoing contrast extravasation on CT angiography (spot sign) can identify individuals with ongoing bleeding who may benefit from anti-fibrinolytic therapy. We aimed to investigate the effect of tranexamic acid on hematoma growth in patients with spot signs treated within 4.5 hours of onset.
We conducted a systematic review and individual patient meta-analysis, which we report according to the Preferred Reporting Items for Systematic Review and Meta-analyses of Individual Participant Data guidelines. PubMed and Embase were searched from inception to May 29, 2023, using the terms ((stroke) AND (randomised OR randomized) AND (tranexamic acid) AND (haemorrhage OR hemorrhage)). We included randomized trials comparing tranexamic acid with placebo in participants with primary intracerebral hemorrhage who had a spot sign and who had follow-up imaging within the required timeframe. Individual patient data were provided by each study and were integrated by the coordinating center. Data were pooled using a random-effects model. The primary endpoint was hematoma growth within 24 hours, defined as ≥33% relative or ≥6 mL absolute hematoma expansion compared with baseline, analyzed using mixed-effects-modified Poisson regression with robust standard errors, adjusted for baseline hematoma volume. Safety outcomes were mortality and major thromboembolic events within 90 days.
Of 197 studies identified, 3 were eligible, contributing 162 participants for the primary analysis (60 female and 102 male). Hematoma growth occurred in 36 of 74 (49%) participants treated with tranexamic acid, compared with 48 of 88 (55%) participants treated with placebo (adjusted risk ratio 0.86, 95% CI 0.84-0.89, < 0.001). Adjusted median absolute hematoma growth was 1.60 mL (95% CI 0.77-2.43) lower with tranexamic acid vs placebo. No differences in functional outcome or safety were observed.
Tranexamic acid modestly reduced hematoma growth in patients with CT angiography spot signs treated within 4.5 hours of onset. Given the trials in the meta-analysis were individually neutral, these results require further validation before clinical application.
抗纤维蛋白溶解剂氨甲环酸在脑出血试验中进行了测试，结果总体上为中性。CT 血管造影（斑点征）上持续的对比外渗可以识别出持续出血的个体，他们可能受益于抗纤维蛋白溶解治疗。我们旨在研究在发病后 4.5 小时内接受治疗的有斑点征的患者中氨甲环酸对血肿增长的影响。
我们进行了系统评价和个体患者荟萃分析，我们根据个体参与者数据系统评价和荟萃分析的首选报告项目报告。从 2023 年 5 月 29 日起，在 PubMed 和 Embase 上使用以下术语进行了搜索：（（中风）和（随机或随机化）和（氨甲环酸）和（出血或出血））。我们纳入了比较原发性脑出血患者中氨甲环酸与安慰剂的随机试验，这些患者有斑点征，且在规定的时间范围内进行了随访成像。每个研究都提供了个体患者数据，并由协调中心进行整合。使用随机效应模型进行数据汇总。主要终点是 24 小时内的血肿增长，定义为与基线相比相对增长≥33%或绝对增长≥6 mL，使用混合效应修正泊松回归进行分析，采用稳健标准误差，根据基线血肿量进行调整。安全性结局是 90 天内的死亡率和主要血栓栓塞事件。
在确定的 197 项研究中，有 3 项符合条件，为主要分析提供了 162 名参与者（60 名女性和 102 名男性）。氨甲环酸治疗的 74 名参与者中有 36 名（49%）发生血肿增长，而安慰剂治疗的 88 名参与者中有 48 名（55%）发生（调整风险比 0.86，95%置信区间 0.84-0.89，<0.001）。与安慰剂相比，氨甲环酸治疗的调整后平均绝对血肿增长低 1.60 毫升（95%置信区间 0.77-2.43）。未观察到功能结局或安全性的差异。
在发病后 4.5 小时内接受治疗的有 CT 血管造影斑点征的患者中，氨甲环酸适度减少了血肿增长。鉴于荟萃分析中的试验单独为中性，在临床应用之前，这些结果需要进一步验证。
