Wenyu Hu1, Yanguo Xin1, Xin Chen2, Zhuyin Song3, Zhiyi He4, Yinan Zhao5. 1. Department of Cardiology, The First Affiliated Hospital of China Medical University, Shenyang, 110001, Liaoning, China. 2. Department of Cardiology, Fuling Central Hospital, Chongqing, 408000, China. 3. Department of Neurology, The People's Hospital of Liaoning Province, Shenyang, 110016, Liaoning, China. 4. Department of Neurology, The First Affiliated Hospital of China Medical University, Shenyang, 110001, Liaoning, China. 5. Department of Neurology, The First Affiliated Hospital of China Medical University, Shenyang, 110001, Liaoning, China. zhaoyinan1616@yahoo.co.jp.
Abstract
BACKGROUND: Tranexamic acid functions as an antifibrinolytic medication and is widely used to treat or prevent excessive blood loss in menorrhagia and during the perioperative period. The efficacy of tranexamic acid in reducing mortaligy and disability, and the occurrence of complications during treatment of cerebral hemorrhage remains controversial. OBJECTIVE: The objective of this systematic literature review and meta-analysis was to evaluate the efficacy and safety of tranexamic acid in patients with cerebral hemorrhage, aiming to improve the evidence-based medical knowledge of treatment options for such patients. METHODS: A systematic literature search was performed in English through 31 August 2018, with two reviewers independently extracting data and assessing risk of bias. We extracted efficacy and safety outcomes and performed a meta-analysis. Statistical tests were performed to check for heterogeneity and publication bias. RESULTS: In total, 14 randomized controlled trials with 4703 participants were included in the meta-analysis. Tranexamic acid did not improve mortality by day 90 (odds ratio (OR) 0.99; 95% confidence interval (CI) 0.84-1.18; p = 0.95) or day 180 (OR 1.01; 95% CI 0.51-2.01; p = 0.98) or overall death endpoints of different follow-up times (OR 0.82; 95% CI 0.62-1.08; p = 0.15), which was supported by sensitivity analysis of studies published during or after 2000 (OR 0.92; 95% CI 0.77-1.09; p = 0.33). A lower incidence of hematoma expansion (OR 0.54; 95% CI 0.37-0.80; p = 0.002) and less change in volume from baseline (mean difference (MD) - 1.98; 95% CI - 3.00 to - 0.97; p = 0.0001) were observed, but no change was seen in poor functional outcomes (OR 0.95; 95% CI 0.79-1.14; p = 0.55) in the tranexamic acid group. The risk of hydrocephalus (OR 1.21; 95% CI 0.90-1.62; p = 0.21), ischemic stroke (OR 1.43; 95% CI 0.87-2.34; p = 0.16), deep vein thrombosis (OR 1.25; 95% CI 0.75-2.08; p = 0.40), and pulmonary embolism (OR 0.97; 95% CI 0.59-1.58; p = 0.89) was similar, whereas the risk of combined ischemic events increased in the tranexamic acid group (OR 1.47; 95% CI 1.07-2.01; p = 0.02). CONCLUSIONS: Treatment with tranexamic acid could reduce rebleeding and hematoma expansion in cerebral hemorrhage without an increase in single ischemic adverse events, but it could increase the risk of combined ischemic events; however, the lack of improvement in mortality and the poor functional outcomes limit the value of clinical application. These findings indicate that the most pertinent issue is the risk-to-benefit ratio with tranexamic acid treatment in cerebral hemorrhage.
BACKGROUND:Tranexamic acid functions as an antifibrinolytic medication and is widely used to treat or prevent excessive blood loss in menorrhagia and during the perioperative period. The efficacy of tranexamic acid in reducing mortaligy and disability, and the occurrence of complications during treatment of cerebral hemorrhage remains controversial. OBJECTIVE: The objective of this systematic literature review and meta-analysis was to evaluate the efficacy and safety of tranexamic acid in patients with cerebral hemorrhage, aiming to improve the evidence-based medical knowledge of treatment options for such patients. METHODS: A systematic literature search was performed in English through 31 August 2018, with two reviewers independently extracting data and assessing risk of bias. We extracted efficacy and safety outcomes and performed a meta-analysis. Statistical tests were performed to check for heterogeneity and publication bias. RESULTS: In total, 14 randomized controlled trials with 4703 participants were included in the meta-analysis. Tranexamic acid did not improve mortality by day 90 (odds ratio (OR) 0.99; 95% confidence interval (CI) 0.84-1.18; p = 0.95) or day 180 (OR 1.01; 95% CI 0.51-2.01; p = 0.98) or overall death endpoints of different follow-up times (OR 0.82; 95% CI 0.62-1.08; p = 0.15), which was supported by sensitivity analysis of studies published during or after 2000 (OR 0.92; 95% CI 0.77-1.09; p = 0.33). A lower incidence of hematoma expansion (OR 0.54; 95% CI 0.37-0.80; p = 0.002) and less change in volume from baseline (mean difference (MD) - 1.98; 95% CI - 3.00 to - 0.97; p = 0.0001) were observed, but no change was seen in poor functional outcomes (OR 0.95; 95% CI 0.79-1.14; p = 0.55) in the tranexamic acid group. The risk of hydrocephalus (OR 1.21; 95% CI 0.90-1.62; p = 0.21), ischemic stroke (OR 1.43; 95% CI 0.87-2.34; p = 0.16), deep vein thrombosis (OR 1.25; 95% CI 0.75-2.08; p = 0.40), and pulmonary embolism (OR 0.97; 95% CI 0.59-1.58; p = 0.89) was similar, whereas the risk of combined ischemic events increased in the tranexamic acid group (OR 1.47; 95% CI 1.07-2.01; p = 0.02). CONCLUSIONS: Treatment with tranexamic acid could reduce rebleeding and hematoma expansion in cerebral hemorrhage without an increase in single ischemic adverse events, but it could increase the risk of combined ischemic events; however, the lack of improvement in mortality and the poor functional outcomes limit the value of clinical application. These findings indicate that the most pertinent issue is the risk-to-benefit ratio with tranexamic acid treatment in cerebral hemorrhage.