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Tranexamic Acid in Cerebral Hemorrhage: A Meta-Analysis and Systematic Review

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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.

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Acknowledgements

The authors gratefully acknowledge financial support from the China Scholarship Council.

Author information

Authors and Affiliations

  1. Department of Cardiology, The First Affiliated Hospital of China Medical University, Shenyang, 110001, Liaoning, China

    Wenyu Hu & Yanguo Xin

  2. Department of Cardiology, Fuling Central Hospital, Chongqing, 408000, China

    Xin Chen

  3. Department of Neurology, The People’s Hospital of Liaoning Province, Shenyang, 110016, Liaoning, China

    Zhuyin Song

  4. Department of Neurology, The First Affiliated Hospital of China Medical University, Shenyang, 110001, Liaoning, China

    Zhiyi He & Yinan Zhao

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  1. Wenyu Hu
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Corresponding author

Correspondence to Yinan Zhao.

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Funding

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.

Electronic supplementary material

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Supplementary material 1 (DOC 38 kb)

40263_2019_608_MOESM2_ESM.tif

Supplementary Fig. 1 Forest plots of Odds Ratio in tranexamic acid group and placebo treatment group for mortality at different following-up time points. Horizontal lines are 95% confidence intervals (TIFF 20486 kb)

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Supplementary Fig. 2 Forest plots of Odds Ratio in tranexamic acid group and placebo treatment group for mortality within 8 hours and within 96 hours administration. Horizontal lines are 95% confidence intervals (TIFF 10374 kb)

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Supplementary Fig. 3 Forest plots of Odds Ratio in tranexamic acid group and placebo treatment group for poor functional outcomes within 8 hours and within 96 hours administration. Horizontal lines are 95% confidence intervals (TIFF 8613 kb)

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Supplementary Fig. 4 Forest plots of Odds Ratio in tranexamic acid group and placebo treatment group for HE in different cerebral hemorrhage types. Horizontal lines are 95% confidence intervals (PNG 34 kb)

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Supplementary Fig. 5 Forest plots of Odds Ratio in tranexamic acid group and placebo treatment group for HE within 30 minutes interval and more than 30 minutes interval administration of tranexamic acid and placebo. Horizontal lines are 95% confidence intervals (TIFF 8650 kb)

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Supplementary Fig. 6 Forest plots of Odds Ratio in tranexamic acid group and placebo treatment group for change in hematoma volume from baseline. Horizontal lines are 95% confidence intervals (TIFF 8472 kb)

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Supplementary Fig. 7 Forest plots of Odds Ratio in tranexamic acid group and placebo treatment group for mortality including studies after 2000. Horizontal lines are 95% confidence intervals (TIFF 4879 kb)

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Supplementary Fig. 8 Forest plots of Odds Ratio in tranexamic acid group and placebo treatment group for adverse events. Horizontal lines are 95% confidence intervals (TIFF 22732 kb)

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Supplementary Fig. 9 Fixed-effects univariate meta-regression between age and the mean difference in tranexamic acid impact between groups. Each circle represents a study and the size of the circle reflects the influence of that study on the model (inversely proportionate to the SE of that study). The regression prediction is represented by the solid line (Coef=0.02, 95%CI=-0.02 to 0.05, p=0.259) (TIFF 8395 kb)

40263_2019_608_MOESM11_ESM.tif

Supplementary Fig. 10 Fixed-effects univariate meta-regression between dignosis and the mean difference in tranexamic acid impact between groups. Each circle represents a study and the size of the circle reflects the influence of that study on the model (inversely proportionate to the SE of that study). The regression prediction is represented by the solid line (Coef=0.19, 95%CI=-0.29 to 0.68, p=0.390) (TIFF 8395 kb)

40263_2019_608_MOESM12_ESM.tif

Supplementary Fig. 11 Fixed-effects univariate meta-regression between sex and the mean difference in tranexamic acid impact between groups. Each circle represents a study and the size of the circle reflects the influence of that study on the model (inversely proportionate to the SE of that study). The regression prediction is represented by the solid line (Coef=0.93, 95%CI=-1.56 to 3.42, p=0.406) (TIFF 8401 kb)

40263_2019_608_MOESM13_ESM.tif

Supplementary Fig. 12 Fixed-effects univariate meta-regression between examination method and the mean difference in tranexamic acid impact between groups. Each circle represents a study and the size of the circle reflects the influence of that study on the model (inversely proportionate to the SE of that study). The regression prediction is represented by the solid line (Coef=0.25, 95%CI=-0.84 to 1.34, p=0.616) (TIFF 8395 kb)

40263_2019_608_MOESM14_ESM.tif

Supplementary Fig. 13 Fixed-effects univariate meta-regression between sample size and the mean difference in tranexamic acid impact between groups. Each circle represents a study and the size of the circle reflects the influence of that study on the model (inversely proportionate to the SE of that study). The regression prediction is represented by the solid line (Coef=0.0001, 95%CI=-0.0003 to 0.0005, p=0.548) (TIFF 8395 kb)

40263_2019_608_MOESM15_ESM.tif

Supplementary Fig. 14 Fixed-effects univariate meta-regression between publication year and the mean difference in tranexamic acid impact between groups. Each circle represents a study and the size of the circle reflects the influence of that study on the model (inversely proportionate to the SE of that study). The regression prediction is represented by the solid line (Coef=0.04, 95%CI=-0.20 to 0.29, p=0.691) (TIFF 8395 kb)

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Hu, W., Xin, Y., Chen, X. et al. Tranexamic Acid in Cerebral Hemorrhage: A Meta-Analysis and Systematic Review. CNS Drugs 33, 327–336 (2019). https://doi.org/10.1007/s40263-019-00608-4

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  • DOI: https://doi.org/10.1007/s40263-019-00608-4

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