The Function of Tranexamic Acid to Prevent Hematoma Expansion After Intracerebral Hemorrhage: A Systematic Review and Meta-Analysis From Randomized Controlled Trials
Frontiers in neurology. 2021;12:710568
Objectives: The clinical results caused by spontaneous intracerebral hemorrhage (ICH) are disastrous to most patient. As tranexamic acid (TXA) has been proved to decrease the influence of ICH, we conducted this research to explore the function of TXA for the prognosis of ICH compared with placebo. Methods: We searched MEDLINE, Embase, Cochrane Library, and Clinicaltrials.gov for randomized controlled trials (RCTs) that were performed to evaluate TXA vs. placebo for ICH up to February 2021. The data were assessed by Review Manager 5.3 software. The risk ratio (RR) and mean difference were analyzed using dichotomous outcomes and continuous outcomes, respectively, with a fixed effect model. Results: We collected 2,479 patients from four RCTs. Then, we took the change of hematoma volume, modified Rankin Scale (mRS), and adverse events as evaluation standard of the treatment for ICH. Through statistical analysis, we found that there is no obvious hematoma expansion effect after the application of TXA (RR = 1.05), and we proceeded the quantitative analysis of percentage change in hematoma volume from baseline, indicating that TXA could inhibit the expansion of hematoma volume (RR = -2.02) compared with placebo. However, according to the outcomes of mRS (0-1, RR = 1.04; 0-2, RR = 0.96), TXA cannot improve neurological functional prognosis. As for the security outcomes-mortality (RR = 1.02), thromboembolic events (RR = 0.99), neurological deterioration (RR = 0.92), infection (RR = 0.86), and craniotomy (RR = 0.41), there seems exist no statistical difference between TXA and placebo. Conclusions: TXA has an advantage in the aspect of preventing hematoma expansion compared with placebo for ICH, but cannot illustrate the efficacy of TXA in improving neurological functional prognosis, which still needs more researches with large sample sizes. Moreover, for safety, we did not find obvious statistical difference between TXA and placebo.
Tranexamic Acid in Intracerebral Hemorrhage: A Meta-Analysis
The International journal of neuroscience. 2021;:1-12
Background ：Tranexamic acid（TA） is an antifibrinolytic agent, which has shown an effect on reducing blood loss in many diseases. Tranexamic acid might be beneficial for intracerebral hemorrhage（ICH）. However, whether TA can treatment of intracerebral hemorrhage is still controversial.Objective: Evidence-based medicine was used to evaluate the efficacy and safety of tranexamic acid in patients with intracerebral hemorrhage.Methods: Pubmed (MEDLINE), Embase, and Cochrane Library were searched from January 2001 to October 2020 for randomized controlled trials (RCTs),cohort studies, and retrospective case series .The Jadad scale and RevMan software version 5.3 were used for literature quality assessment and meta-analysis.Results: In total, 4 randomized controlled trials and 1 retrospective case series with 2808 participants were included in the meta-analysis. Compared with control intervention in intracerebral hemorrhage, tranexamic acid could significantly reduce growth of hemorrhagic mass (odds ratio (OR) =0.81; 95% confidence interval（CI）=0.68 to 0.99; p = 0.04) and Modified Rankin Scale score(MRS) at 90 days at 0-3 (OR =1.20; 95% CI =1.00 to 1.43; p = 0.05), mortality by day 90 (OR= 1.03; 95% CI= 0.85-1.25; p = 0.77) and major thromboembolic events (OR= 1.14; 95% CI= 0.73-1.77; p = 0.58) .Conclusions:Treatment with tranexamic acid could reduce hematoma expansion in intracerebral hemorrhage,and the treatment was safe with no increase in thromboembolic complications. But showed no notable impact on good functional outcomes and mortality.
Safety and Efficacy of Tranexamic Acid in Aneurysmal Subarachnoid Hemorrhage: A Meta-Analysis of Randomized Controlled Trials
Frontiers in neurology. 2021;12:710495
BACKGROUND In recent decades, tranexamic acid (TXA) antifibrinolytic therapy before aneurysm clipping or embolization has been widely reported, but its safety and efficacy remain controversial. This meta-analysis evaluated the efficacy and safety of TXA therapy in aneurysmal subarachnoid hemorrhage (aSAH) patients, aiming to improve the evidence-based medical knowledge of treatment options for such patients. METHODS Pubmed, Web of Science, and Cochrane Library databases were searched up to 1 March 2021 for randomized controlled trials (RCTs). We extracted safety and efficacy outcomes and performed a meta-analysis using the Review Manager software. We performed two group analyses of TXA duration and daily dose. RESULTS Ten RCT studies, enrolling a total of 2,810 participants (1,410 with and 1,400 without TXA therapy), matched the selection criteria. In the TXA duration group: TXA did not reduce overall mortality during the follow-up period [RR 1.00 (95% CI 0.81-1.22)]. The overall rebleeding rate in the TXA group was 0.53 times that of the control group, which was statistically significant [RR 0.53 (95% CI 0.39-0.71)]. However, an RR of 0.43 was not statistically significant in the subgroup analysis of short-term therapy [RR 0.43 (95% CI 0.13-1.39)]. The overall incidence of hydrocephalus was significantly higher in the TXA group than in the control group [RR 1.13 (95% CI 1.02-1.24)]. However, the trend was not statistically significant in the subgroup analysis [short-term: RR 1.10 (95% CI 0.99-1.23); long-term: RR 1.22 (95% CI 0.99-1.50)]. Treatment with TXA did not cause significant delayed cerebral ischemia [RR 1.18 (95% CI 0.89-1.56)], and its subgroup analysis showed an opposite and insignificant effect [short-term: RR 0.99 (95% CI 0.79-1.25); long-term: RR 1.38 (95% CI 0.86-2.21)]. Results in the daily dose group were consistent with those in the TXA duration group. CONCLUSIONS Tranexamic acid does not reduce overall mortality in patients with aSAH, nor does it increase the incidence of delayed cerebral ischemia. Tranexamic acid in treating aSAH can reduce the incidence of rebleeding. However, there is no statisticalsignificance in the ultra-early short-term and low daily dose TXA therapy, which may be due to the lack of relevant studies, and more RCT experiments are needed for further study. SYSTEMATIC REVIEW REGISTRATION https://www.crd.york.ac.uk/PROSPERO/display_record.asp? PROSPERO, identifier: 244079.
Aneurysmal subarachnoid haemorrhage patients (10 studies, n= 2,810).
Tranexamic acid (TXA), (n= 1,410).
Conventional treatment without TXA (n= 1,400).
The overall re-bleeding rate in the TXA group was 0.53 times that of the control group. The overall incidence of hydrocephalus was significantly higher in the TXA group than in the control group. Treatment with TXA did not cause significant delayed cerebral ischemia.
Tranexamic Acid for Acute Spontaneous Intracerebral Hemorrhage: A Meta-Analysis of Randomized Controlled Trials
Frontiers in neurology. 2021;12:761185
Background: The role of tranexamic acid (TXA) in preventing hematoma expansion (HE) in patients with acute spontaneous intracerebral hemorrhage (ICH) remains unclear. We aim to investigate the efficacy and safety of TXA in acute spontaneous ICH with a particular focus on subgroups. Methods: Randomized controlled trials (RCTs) were retrieved from CENTRAL, Clinicaltrials.gov, EMBASE, PubMed, and WHO ICTRP. The primary outcome measurement was HE. The secondary outcome measurements included 3-month poor functional outcome (PFO), 3-month mortality, and major thromboembolic events (MTE). We conducted subgroup analysis according to the CT markers of HE (standard-risk population and high-risk population) and the time from onset to randomization (>4.5 and ≤4.5 h). Results: We identified seven studies (representing five RCTs) involving 2,650 participants. Compared with placebo, TXA may reduce HE on subsequent imaging (odd ratio [OR] 0.825; 95% confidence interval [CI] 0.692-0.984; p = 0.033; I(2) = 0%; GRADE moderate certainty). TXA and placebo arms did not differ in the rates of 3-month PFO, 3-month mortality, and MTE. Subgroup analysis indicated that TXA reduced the risk of HE in the high-risk population with CT markers of HE (OR 0.646; 95% CI 0.503-0.829; p = 0.001; I(2) = 0 %) and in patients who were treated within 4.5 h of symptom onset (OR 0.823; 95% CI 0.690-0.980; p = 0.029; I(2) = 0%), but this protective effect was not observed in the standard-risk population and patients who were treated over 4.5 h of symptom onset. Conclusions: Tranexamic acid (TXA) may decrease the risk of HE in patients with acute spontaneous ICH. Importantly, the decreased risk was observed in patients who were treatable within 4.5 h and with a high risk of HE, but not in those who were treatable over 4.5 h and in standard-risk population. However, PFO or mortality at 3 months did not significantly differ between patients who received TXA and those who received placebo. TXA is safe for acute spontaneous ICH without increasing MTE.
Tranexamic acid for subarachnoid hemorrhage: A systematic review and meta-analysis
The American journal of emergency medicine. 2021;50:748-752
BACKGROUND The efficacy of tranexamic acid for subarachnoid hemorrhage remains controversial. Thus, we conduct this meta-analysis to explore the efficacy of tranexamic acid for subarachnoid hemorrhage. METHODS PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases were systematically searched. Randomized controlled trials (RCTs) assessing the effect of tranexamic acid on subarachnoid hemorrhage were included. Two investigators independently searched articles, extracted data, and assessed the quality of included studies. This meta-analysis was performed using the random-effect model. RESULTS Five RCTs and 2359 patients were included in the meta-analysis. Overall, compared with control intervention for subarachnoid hemorrhage, tranexamic acid was associated with significantly reduced risk of rebleeding (Odd ratio [OR] =0.62; 95% confidence interval [CI] =0.41 to 0.93; P = 0.02), but had no influence on mortality (OR = 0.94; 95% CI = 0.75 to 1.18; P = 0.61), poor outcome (OR = 0.95; 95% CI = 0.61 to 1.48; P = 0.82), hydrocephalus (OR = 1.17; 95% CI = 0.94 to 1.46; P = 0.17) or delayed cerebral ischemia (OR = 1.26; 95% CI = 0.78 to 2.04; P = 0.34). CONCLUSIONS Tranexamic acid may be effective to reduce the risk of rebleeding in patients with subarachnoid hemorrhage.
Efficacy and Safety of Tranexamic Acid in Aneurysmal Subarachnoid Hemorrhage: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Frontiers in surgery. 2021;8:790149
Tranexamic acid has been shown to reduce rebleeding after aneurysmal subarachnoid hemorrhage; however, whether it can reduce mortality and improve clinical outcomes is controversial. We performed a systematic review and meta-analysis to evaluate the efficacy and safety of the tranexamic acid in aneurysmal subarachnoid hemorrhage. We conducted a comprehensive literature search of PubMed, Embase, Web of Science, and Cochrane Library from inception to March 2021 for randomized controlled trials (RCTs) comparing tranexamic acid and placebo in adults with aneurysmal subarachnoid hemorrhage. The risk of bias was evaluated using the Cochrane Handbook, and the quality of evidence was evaluated using the GRADE approach. This meta-analysis included 13 RCTs, involving 2,888 patients. In patients with aneurysmal subarachnoid hemorrhage tranexamic acid had no significant effect on all-cause mortality (RR = 0.96; 95% CI = 0.84-1.10, p = 0.55, I (2) = 44%) or poor functional outcome (RR = 1.04; 95% CI = 0.95-1.15, p = 0.41) compared with the control group. However, risk of rebleeding was significantly lower (RR = 0.59; 95% CI = 0.43-0.80, p = 0.0007, I (2) = 53%). There were no significant differences in other adverse events between tranexamic acid and control treatments, including cerebral ischemia (RR = 1.17; 95% CI = 0.95-1.46, p = 0.15, I (2) = 53%). At present, routine use of tranexamic acid after subarachnoid hemorrhage cannot be recommended. For a patient with subarachnoid hemorrhage, it is essential to obliterate the aneurysm as early as possible. Additional higher-quality studies are needed to further assess the effect of tranexamic acid on patients with subarachnoid hemorrhage.
Efficacy and safety of tranexamic acid in aneurysmal subarachnoid hemorrhage: A meta-analysis of randomized controlled trials
The American journal of emergency medicine. 2021;50:646-653
INTRODUCTION Tranexamic acid, as a traditional hemostatic agent, is commonly used to treat or prevent excessive blood loss. However, the role of tranexamic acid in promoting good clinical outcomes and reducing mortality and risk of adverse events during the treatment of aneurysmal subarachnoid hemorrhage remains unclear. METHODS In strict accordance with the inclusion and exclusion criteria, Cochrane Library, Embase, Web of Science, and PubMed databases were assessed for randomized controlled trials (published between 1980 and 2021). Data were analyzed using STATA 16.0 and RevMan 5.3. In addition, the fixed-effects model (M-H method) and effect size (risk difference; RD) were used as a pooled measure to combine data. We also performed a post hoc sensitivity analysis and subgroup analysis to evaluate each outcome with low heterogeneity. RESULTS A meta-analysis revealed that although tranexamic acid was related to less rebleeding (RD = -0.06; 95% CI [-0.09, -0.03]; P = 0.0006), there is evidence that it has no an effect on good clinical outcomes or mortality (RD = -0.01; 95% CI [-0.05, 0.02]; P = 0.51; RD = 0.00; 95% CI [-0.03, 0.04]; P = 0.91). Tranexamic acid was associated with increased hydrocephalus (RD = 0.04; 95% CI [0.01, 0.08]; P = 0.02) and seizure (RD = 0.04; 95% CI [0.00, 0.08]; P = 0.05). The incidence of thromboembolic complications or delayed cerebral ischemia was not different in the two groups (RD = -0.01; 95% CI [-0.04, 0.03]; P = 0.62; RD = 0.00; 95% CI [-0.03, 0.03]; P = 0.96), and significant drug-related overall adverse events were identified (RD = 0.02; 95% CI [0.00, 0.04]; P = 0.03). CONCLUSIONS These findings indicate that the routine use of tranexamic acid is not suggested for patients with aneurysmal subarachnoid hemorrhage.
Tranexamic acid in non-traumatic intracranial bleeding: a systematic review and meta-analysis
Scientific reports. 2021;11(1):15275
Non-traumatic intracranial bleeding (NTIB), comprising subarachnoid hemorrhage (SAH) and intra-cranial bleeding (ICH) is a significant public health concern. Tranexamic acid (TXA) is a promising treatment with benefits yet to be fully demonstrated. We conducted a systematic review and meta-analysis on the impact of TXA on mortality in NTIB. We searched the PubMed, Cochrane Library, Google Scholar and ScienceDirect databases for studies reporting mortality data following the use of TXA in NTIB for comparisons with a control group. We computed random-effect meta-analysis on estimates of risk and sensitivity analyses. We computed meta-regression to examine the putative effects of the severity of NTIB, sociodemographic data (age, sex), and publication date. Among potentially 10,008 articles, we included 15 studies representing a total of 4883 patients: 2455 receiving TXA and 2428 controls; 1110 died (23%) during the follow-up. The meta-analysis demonstrated a potential of 22% decrease in mortality for patients treated by TXA (RR = 0.78, 95%CI 0.58-0.98, p = 0.002). Meta-regression did not demonstrate any influence of the severity of NTIB, age, sex, length of treatment or date of publication. Sensitivity analyses confirmed benefits of TXA on mortality. TXA appears to be a therapeutic option to reduce non-traumatic intracranial bleeding mortality, particularly in patients with SAH.
Influence of tranexamic acid on cerebral hemorrhage: A meta-analysis of randomized controlled trials
Clinical Neurology and Neurosurgery. 2018;(171):174-178.
Tranexamic acid might be beneficial for cerebral hemorrhage. However, the results remained controversial. We conducted a systematic review and meta-analysis to explore the influence of tranexamic acid on cerebral hemorrhage. PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases were systematically searched. Randomized controlled trials (RCTs) assessing the effect of tranexamic acid on cerebral hemorrhage were included. Two investigators independently searched articles, extracted data, and assessed the quality of included studies. This meta-analysis was performed using the random-effect model. Seven RCTs involving 1702 patients were included in the meta-analysis. Overall, compared with control intervention in cerebral hemorrhage, tranexamic acid could significantly reduce growth of hemorrhagic mass (RR=0.78; 95% CI=0.61-0.99; P=0.04) and unfavorable outcome (RR=0.75; 95% CI=0.61-0.93; P=0.008), but demonstrated no substantial influence on volume of hemorrhagic lesion (Std. MD=-0.10; 95% CI=-0.27 to 0.08; P=0.28), neurologic deterioration (RR=1.25; 95% CI=0.60-2.60; P=0.56), rebleeding (RR=0.62; 95% CI=0.35-1.09; P=0.10), surgery requirement (RR=0.78; 95% CI=0.40-1.51; P=0.46), and mortality (RR=0.86; 95% CI=0.69-1.05; P=0.14). Compared to control intervention in cerebral hemorrhage, tranexamic acid was found to significantly decrease growth of hemorrhagic mass and unfavorable outcome, but showed no notable impact on volume of hemorrhagic lesion, neurologic deterioration, rebleeding, surgery requirement and mortality.
Evidence for the use of tranexamic acid in subarachnoid and subdural hemorrhage: a systematic review
Seminars in Thrombosis and Hemostasis. 2017;43((7):):750-758