Tranexamic Acid in Cerebral Hemorrhage: A Meta-Analysis and Systematic Review
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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.
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.
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.
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).
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.
The authors gratefully acknowledge financial support from the China Scholarship Council.
Compliance with Ethical Standards
No sources of funding were used to conduct this study or prepare this manuscript.
Conflict of interest
Wenyu Hu, Yanguo Xin, Xin Chen, Zhuyin Song, Zhiyi He, and Yinan Zhao have no potential conflicts of interest that might be relevant to the contents of this manuscript.
- 3.Mendelow AD, Gregson BA, Fernandes HM, Murray GD, Teasdale GM, Hope DT, et al. Early surgery versus initial conservative treatment in patients with spontaneous supratentorial intracerebral haematomas in the International Surgical Trial in Intracerebral Haemorrhage (STICH): a randomised trial. Lancet. 2005;365(9457):387–97.CrossRefGoogle Scholar
- 8.Roberts I, Shakur H, Ker K, Coats T, Roberts I. Antifibrinolytic drugs for acute traumatic injury. Cochrane Database Syst Rev. 2012;12:CD004896.Google Scholar
- 11.CRASH-2 trial collaborators, Shakur H, Roberts I, Bautista R, Caballero J, et al. Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): a randomised, placebo-controlled trial. Lancet. 2010;376(9734):23–32.CrossRefGoogle Scholar
- 24.Perel P, Al-Shahi Salman R, Kawahara T, Morris Z, Prieto-Merino D, Roberts I, et al. CRASH-2 (Clinical Randomisation of an Antifibrinolytic in Significant Haemorrhage) intracranial bleeding study: the effect of tranexamic acid in traumatic brain injury—a nested randomised, placebo-controlled trial. Health Technol Assess. 2012;16(13):iii–vii, 1–54.CrossRefGoogle Scholar
- 26.Arumugam A, Rahman NAA, Theophilus SC, Shariffudin A, Abdullah JM. Tranexamic acid as antifibrinolytic agent in non traumatic intracerebral hemorrhages. Malays J Med Sci. 2015;22:62–71.Google Scholar
- 30.Gayet-Ageron A, Prieto-Merino D, Ker K, Shakur H, Ageron F-X, Roberts I, et al. Effect of treatment delay on the effectiveness and safety of antifibrinolytics in acute severe haemorrhage: a meta-analysis of individual patient-level data from 40 138 bleeding patients. Lancet. 2018;391(10116):125–32.CrossRefGoogle Scholar
- 31.Baharoglu MI, Germans MR, Rinkel GJ, Algra A, Vermeulen M, van Gijn J, et al. Antifibrinolytic therapy for aneurysmal subarachnoid haemorrhage. Cochrane Database Syst Rev. 2013;8:CD001245.Google Scholar