Lee Seungjoo, Kim Moinay, Kwon Sae Min, Kwon Min-Yong, Kim Chang-Hyun, Son Nak-Hoon, Kim Jae Hyun
Department of Neurosurgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Department of Neurosurgery, Keimyung University School of Medicine, 1035, Dalgubeol-daero, Dalseo-gu, Daegu, Republic of Korea.
CNS Drugs. 2025 May 2. doi: 10.1007/s40263-025-01185-5.
Tranexamic acid (TXA) is widely used to manage acute brain injuries, including subarachnoid hemorrhage, intracerebral hemorrhage, and traumatic brain injury. Despite its common usage, there is limited evidence on its safety in these conditions. We aimed to evaluate the impact of TXA on mortality and thromboembolic events in patients with acute brain injury.
A systematic search of MEDLINE/PubMed, Embase, and the Cochrane Central Register of Controlled Trials was conducted from inception to May 2024. We included randomized controlled trials (RCTs) comparing TXA with placebo in patients aged 15 years or older with confirmed acute brain injury. Two reviewers independently assessed study quality using the revised Cochrane Risk of Bias tool and extracted data on patient demographics, intervention details, and outcomes, including mortality, thromboembolic events, and seizures. Meta-analyses were performed using random effects models.
Twenty-five RCTs with 16,677 participants (8584 TXA, 8093 control) were included. The relative risk (RR) for overall mortality was 0.96 (95% confidence interval (CI) 0.91-1.03, p = 0.2433), indicating a nonsignificant difference between the groups, with no substantial heterogeneity (I = 0% [0-45%]). Additionally, no significant differences were observed in 30-, 90-, or 180-day mortality. The RR for total thromboembolic events was 1.11 (95% CI 0.97-1.28, p = 0.1236), indicating a nonsignificant difference between the groups, with low heterogeneity (I = 15% [0-51%]). Similarly, no significant differences were observed in the incidences of deep vein thrombosis or pulmonary embolism, ischemic stroke or transient ischemic attack, acute coronary syndrome or myocardial infarction, or seizures. However, the administration of TXA for more than 1 day was associated with a significant increase in thromboembolic events (RR 1.22, 95% CI 1.03-1.44). Administering TXA beyond 8 h of injury was also associated with a significant increase in thromboembolic events (RR 1.16, 95% CI 1.02-1.33).
TXA administration does not significantly affect overall mortality or increase the risk of thromboembolic events in patients with acute brain injuries. However, prolonged use or delayed administration may be associated with an increased risk of thromboembolic events. These findings highlight the need for careful consideration of the duration and timing of TXA administration in clinical practice.
氨甲环酸（TXA）被广泛用于治疗急性脑损伤，包括蛛网膜下腔出血、脑出血和创伤性脑损伤。尽管其使用普遍，但在这些情况下其安全性的证据有限。我们旨在评估TXA对急性脑损伤患者死亡率和血栓栓塞事件的影响。
从创刊至2024年5月，对MEDLINE/PubMed、Embase和Cochrane对照试验中央注册库进行了系统检索。我们纳入了在15岁及以上确诊为急性脑损伤的患者中比较TXA与安慰剂的随机对照试验（RCT）。两名研究者使用修订后的Cochrane偏倚风险工具独立评估研究质量，并提取有关患者人口统计学、干预细节和结局的数据，包括死亡率、血栓栓塞事件和癫痫发作。使用随机效应模型进行荟萃分析。
纳入了25项RCT，共16677名参与者（8584名使用TXA，8093名作为对照）。总体死亡率的相对风险（RR）为0.96（95%置信区间（CI）0.91 - 1.03，p = 0.2433），表明两组之间无显著差异，且无实质性异质性（I² = 0% [0 - 45%]）。此外，在30天、90天或180天死亡率方面未观察到显著差异。总血栓栓塞事件的RR为1.11（95% CI 0.97 - 1.28，p = 0.1236），表明两组之间无显著差异，异质性较低（I² = 15% [0 - 51%]）。同样，在深静脉血栓形成或肺栓塞、缺血性中风或短暂性脑缺血发作、急性冠状动脉综合征或心肌梗死或癫痫发作的发生率方面未观察到显著差异。然而，TXA使用超过1天与血栓栓塞事件显著增加相关（RR 1.22，95% CI 1.03 - 1.44）。在损伤8小时后给予TXA也与血栓栓塞事件显著增加相关（RR 1.16，95% CI 1.02 - 1.33）。
给予TXA对急性脑损伤患者的总体死亡率没有显著影响，也不会增加血栓栓塞事件的风险。然而，长期使用或延迟给药可能与血栓栓塞事件风险增加相关。这些发现凸显了在临床实践中仔细考虑TXA给药持续时间和时机的必要性。
