Abstract

AIM: The efficacy of antifibrinolytics in subarachnoid hemorrhage remains unclear due to conflicting evidence from studies. MATERIALS & METHODS Online databases were queried to include randomized controlled trials and propensity matched observational studies. We used Review Manager for the statistical analysis, presenting results as odds ratios with 95% CI. RESULTS The 12 shortlisted studies included 3359 patients, of which 1550 (46%) were in the intervention (tranexamic acid) group and 1809 (54%) in the control group. Antifibrinolytic therapy significantly reduced the risk of rebleeding (OR: 0.55; 95% CI: 0.40-0.75; p = 0.0002) with no significant decrease in poor clinical outcome (OR: 1.02; 95% CI: 0.86-1.20; p = 0.85) and all-cause mortality (OR: 0.92; CI: 0.72-1.17; p = 0.50). CONCLUSION In patients with subarachnoid hemorrhage, antifibrinolytics reduce the risk of rebleeding without significantly affecting mortality or clinical outcomes.

Abstract

BACKGROUND Although some studies have shown that tranexamic acid is beneficial to patients with intracranial haemorrhage, the efficacy and safety of tranexamic acid for intracranial haemorrhage remain controversial. METHOD The PubMed, EMBASE, and Cochrane Library databases were systematically searched. The review followed PRISMA guidelines. Data were analyzed using the random-effects model. RESULTS Twenty-five randomized controlled trials were included. Tranexamic acid significantly inhibited hematoma growth in intracranial hemorrhage (ICH) and traumatic brain injury (TBI) patients. (ICH: mean difference -1.76, 95%CI -2.78 to -0.79, I2 = 0%, P < .001; TBI: MD -4.82, 95%CI -8.06 to -1.58, I2 = 0%, P = .004). For subarachnoid hemorrhage (SAH) patients, it significantly decreased the risk of hydrocephalus (OR 1.23, 95%CI 1.01 to 1.50, I2 = 0%, P = .04) and rebleeding (OR, 0.52, 95%CI 0.35 to 0.79, I2 = 56% P = .002). There was no significance in modified Rankin Scale, Glasgow Outcome Scale 3-5, mortality, deep vein thrombosis, pulmonary embolism, or ischemic stroke/transient ischemic. CONCLUSION Tranexamic acid can significantly reduce the risk of intracranial haemorrhage growth in patients with ICH and TBI. Tranexamic acid can reduce the incidence of complications (hydrocephalus, rebleeding) in patients with SAH, which can indirectly improve the quality of life of patients with intracranial haemorrhage.

Abstract

OBJECTIVE We aimed to synthesize evidence from published clinical trials on the efficacy and safety of tranexamic acid (TXA) administration in patients with aneurysmal subarachnoid hemorrhage (aSAH). METHODS We followed the standard methods of the Cochrane Handbook of Systematic Reviews for interventions and the PRISMA statement guidelines 2020 when conducting and reporting this study. A computer literature search of PubMed, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials was conducted from inception until 1 January 2022. We selected observational studies and clinical trials comparing TXA versus no TXA in aSAH patients. Data of all outcomes were pooled as the risk ratio (RR) with the corresponding 95% confidence intervals in the meta-analysis models. RESULTS Thirteen studies with a total of 2991 patients were included in the analysis. TXA could significantly cut the risk of rebleeding (RR 0.56, 95% CI 0.44 to 0.72) and mortality from rebleeding (RR 0.60, 95% CI 0.39 to 0.92, p = 0.02). However, TXA did not significantly improve the overall mortality, neurological outcome, delayed cerebral ischemia, or hydrocephalus (all p > 0.05). In terms of safety, no significant adverse events were reported. No statistical heterogeneity or publication bias was found in all outcomes. CONCLUSION In patients with aSAH, TXA significantly reduces the incidence of rebleeding and mortality from rebleeding. However, current evidence does not support any benefits in overall mortality, neurological outcome, delayed cerebral ischemia, or hydrocephalus.

Abstract

BACKGROUND Rebleeding is an important cause of death and disability in people with aneurysmal subarachnoid haemorrhage. Rebleeding is probably related to the dissolution of the blood clot at the site of the aneurysm rupture by natural fibrinolytic activity. This review is an update of previously published Cochrane Reviews. OBJECTIVES To assess the effects of antifibrinolytic treatment in people with aneurysmal subarachnoid haemorrhage. SEARCH METHODS We searched the Cochrane Stroke Group Trials Register (May 2022), CENTRAL (in the Cochrane Library 2021, Issue 1), MEDLINE (December 2012 to May 2022), and Embase (December 2012 to May 2022). In an effort to identify further published, unpublished, and ongoing studies, we searched reference lists and trial registers, performed forward tracking of relevant references, and contacted drug companies (the latter in previous versions of this review). SELECTION CRITERIA Randomised trials comparing oral or intravenous antifibrinolytic drugs (tranexamic acid, epsilon amino-caproic acid, or an equivalent) with control in people with subarachnoid haemorrhage of suspected or proven aneurysmal cause. DATA COLLECTION AND ANALYSIS Two review authors (MRG & WJD) independently selected trials for inclusion, and extracted the data for the current update. In total, three review authors (MIB & MRG in the previous update; MRG & WJD in the current update) assessed risk of bias. For the primary outcome, we dichotomised the outcome scales into good and poor outcome, with poor outcome defined as death, vegetative state, or (moderate) severe disability, assessed with either the Glasgow Outcome Scale or the Modified Rankin Scale. We assessed death from any cause, rates of rebleeding, delayed cerebral ischaemia, and hydrocephalus per treatment group. We expressed effects as risk ratios (RR) with 95% confidence intervals (CI). We used random-effects models for all analyses. We assessed the quality of the evidence with GRADE. MAIN RESULTS We included one new trial in this update, for a total of 11 included trials involving 2717 participants. The risk of bias was low in six studies. Five studies were open label, and we rated them at high risk of performance bias. We also rated one of these studies at high risk for attrition and reporting bias.  Five trials reported on poor outcome (death, vegetative state, or (moderate) severe disability), with a pooled risk ratio (RR) of 1.03 (95% confidence interval (CI) 0.94 to 1.13; P = 0.53; 5 trials, 2359 participants; high-quality evidence), which showed no difference between groups. All trials reported on death from all causes, which showed no difference between groups, with a pooled RR of 1.02 (95% CI 0.90 to 1.16; P = 0.77; 11 trials, 2717 participants; high-quality evidence). In trials that combined short-term antifibrinolytic treatment (< 72 hours) with preventative measures for delayed cerebral ischaemia, the RR for poor outcome was 0.98 (95% CI 0.81 to 1.18; P = 0.83; 2 trials, 1318 participants; high-quality evidence).  Antifibrinolytic treatment reduced the risk of rebleeding, reported at the end of follow-up (RR 0.65, 95% CI 0.47 to 0.91; P = 0.01; 11 trials, 2717 participants; absolute risk reduction 7%, 95% CI 3 to 12%; moderate-quality evidence), but there was heterogeneity (I² = 59%) between the trials. The pooled RR for delayed cerebral ischaemia was 1.27 (95% CI 1.00 to 1.62; P = 0.05; 7 trials, 2484 participants; moderate-quality evidence). However, this effect was less extreme after the implementation of ischaemia preventative measures and < 72 hours of treatment (RR 1.10, 95% CI 0.83 to 1.46; P = 0.49; 2 trials, 1318 participants; high-quality evidence). Antifibrinolytic treatment showed no effect on the reported rate of hydrocephalus (RR 1.09, 95% CI 0.99 to 1.20; P = 0.09; 6 trials, 1992 participants; high-quality evidence). AUTHORS' CONCLUSIONS The current evidence does not support the routine use of antifibrinolytic drugs in the treatment of people with aneurysmal subarachnoid haemorrhage. More specifically, early administration with concomitant treatment strategies to prevent delayed cerebral ischaemia does not improve clinical outcome. There is sufficient evidence from multiple randomised controlled trials to incorporate this conclusion in treatment guidelines.

Abstract

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.

Abstract

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.

Abstract

BACKGROUND The effects of tranexamic acid on spontaneous intracerebral hemorrhage in reducing hematoma expansion and mortality as well as its role in thromboembolic complications and in the improvement of functional outcomes remain substantially uncertain. OBJECTIVE The objective of this systematic review was to evaluate the efficacy and safety of tranexamic acid in patients with spontaneous intracerebral hemorrhage. METHODS Several databases were searched from inception up to 20 June, 2021. We included randomized controlled trials that compared tranexamic acid with placebo or no treatment for the management of intracerebral hemorrhage. The primary outcomes were hematoma expansion and 90-day mortality. The secondary outcomes were hemorrhagic volume change, thromboembolic complications, and functional outcomes. RESULTS Overall, six trials with 2800 patients were included in this meta-analysis. Tranexamic acid was associated with a reduced risk of hematoma expansion (relative risk 0.87, 95% confidence interval [CI] 0.77-0.99, p = 0.03, I(2) = 0%, six trials with 2800 participants) and a lessening of hematoma volume change (mean difference - 1.28, 95% CI - 2.44 to - 0.12; p = 0.03; I(2) = 0%, four trials with 2626 participants), without a corresponding higher rate of major thromboembolic complications (relative risk 1.20, 95% CI 0.85-1.69; p = 0.80; I(2) = 0%, five trials with 2759 participants). The present analysis also demonstrated that tranexamic acid had no effect on reducing 90-day mortality (relative risk 1.02, 95% CI 0.88-1.19; p = 0.80; I(2) = 0%, five trials with 2770 participants). CONCLUSIONS In adults with spontaneous intracerebral hemorrhage, tranexamic acid reduced the risk of intracerebral hemorrhage growth compared with the control. The effects on 90-day mortality remained inconclusive. Further studies should report death within 24 h and death due to bleeding whenever possible.

Abstract

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.

Abstract

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.

Abstract

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.