Is There a Role for Tranexamic Acid in Upper GI Bleeding? A Systematic Review and Meta-Analysis
Surgery research and practice. 2021;2021:8876991
INTRODUCTION Upper gastrointestinal (GI) bleeding is associated with increased morbidity and mortality. Tranexamic acid (TXA) is an antifibrinolytic agent which is licensed in the management of haemorrhage associated with trauma. It has been suggested that tranexamic acid may be able to play a role in upper GI bleeding. However, there is currently no recommendation to support this. AIM: The aim of this study was to synthesise available evidence of the effect of TXA on upper GI bleeding. METHODS AND MATERIALS A systematic review was conducted. PubMed, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) were searched for relevant studies. A random effects meta-analysis was performed to determine the risk ratio of primary and secondary outcomes pertaining to the use of TXA in upper GI bleeding. RESULTS A total of 8 studies were included in this systematic review. The total number of patients in all studies was 12994 including 4550 females (35%) and 8444 males (65%). The mean age of participants in 6 of the studies was 59.3; however the mean age for either intervention or placebo group was not reported in two of the studies. All studies reported on the effect of TXA on mortality, and the risk ratio was 0.95; however, with the 95% CI ranging from 0.80 to 1.13, this was not statistically significant. 6 of the studies reported on rebleeding rate, the risk ratio was 0.64, and with a 95% CI ranging from 0.47 to 0.86, this was statistically significant. 3 of the studies reported on the risk of adverse thromboembolic events, and the risk ratio was 0.93; however, the 95% CI extended from 0.62 to 1.39 and so was not statistically significant. 7 of the studies reported on the need for surgery, and the risk ratio was 0.59 and was statistically significant with a 95% CI ranging from 0.38 to 0.94. CONCLUSION In conclusion, the use of TXA in upper GI bleeding appears to have a beneficial effect in terms of decreasing the risk of re-bleeding and decreasing the need for surgery. However, we could not find a statistically significant effect on need for blood transfusions, risk of thromboembolic events, or effect on mortality. Future randomised controlled trials may elucidate these outcomes.
Patients with upper gastrointestinal (GI) bleeding (8 studies, n= 12,994).
Meta-analysis to synthesise available evidence of the effect of tranexamic acid (TXA) on upper GI bleeding.
All studies reported on the effect of TXA on mortality, and the risk ratio was 0.95; however, this was not statistically significant. 6 of the studies reported on rebleeding rate, the risk ratio was 0.64, and this was statistically significant. 3 of the studies reported on the risk of adverse thromboembolic events, and the risk ratio was 0.93; however, was not statistically significant. 7 of the studies reported on the need for surgery, and the risk ratio was 0.59 and was statistically significant.
Efficacy and safety of tranexamic acid in acute upper gastrointestinal bleeding: meta-analysis of randomised controlled trials
Scandinavian journal of gastroenterology. 2020;:1-8
BACKGROUND Studies evaluating the role of tranexamic acid in acute upper GI bleeding (UGIB) have reported conflicting results. In this systematic review, we have evaluated the efficacy and safety of tranexamic acid in UGIB. METHODS We searched several databases from inception to June 6, 2020 to identify randomised controlled trials (RCTs) that compared tranexamic acid and placebo in UGIB. Our outcomes of interest were mortality, rebleeding, all thromboembolic events, venous thromboembolic events, need for transfusion, endoscopic intervention and surgery. Pooled risk ratios (RR) with 95% confidence intervals (CI) were calculated using fixed effect model. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework to assess the certainty of evidence. RESULTS We included 12 RCTs comprising 14,100 patients. We found no significant difference in mortality, pooled RR (95% CI) 0.87 (0.74-1.01), rebleeding, pooled RR (95% CI) 0.90 (0.79-1.02), need for surgery, pooled RR (95% CI) 0.86 (0.73-1.02), need for transfusion, pooled RR (95% CI) 1.00 (0.99-1.01) or thromboembolic events, RR (95% CI) 1.16 (0.87-1.56) between treatments. We found an increased risk of venous thromboembolic events with tranexamic acid, pooled RR (95% CI) 1.94 (1.23-3.05). Certainty of evidence based on the GRADE framework for the different outcomes ranged from low to very low. CONCLUSIONS Tranexamic acid does not improve outcomes in UGIB and may increase the risk of venous thromboembolic events.
Patients with acute upper gastrointestinal bleeding bleeding (12 studies, n= 14,100).
Tranexamic acid (n= 7101).
Placebo (n= 6999).
No significant difference in mortality, rebleeding, need for surgery, need for transfusion, or thromboembolic events, between treatments was found. However, there was an increased risk of venous thromboembolic events with tranexamic acid.
Tranexamic acid for gastrointestinal bleeding: A systematic review with meta-analysis of randomized clinical trials
The American journal of emergency medicine. 2020
BACKGROUND Acute gastrointestinal bleeding is a common life-threatening emergent condition. Immediate tranexamic acid is useful for reducing hemorrhage following operation and bleeding trauma, but evidence on the effects of tranexamic acid in patients with gastrointestinal bleeding is limited or highly heterogeneous. It is still unclear about using tranexamic acid in the emergent condition of gastrointestinal bleeding. This study, therefore, aimed to determine whether or not tranexamic acid should be used in gastrointestinal bleeding management through systematic review and meta-analysis. METHODS We searched three biomedical databases for relevant randomized controlled trials on this topic. Two authors independently selected studies and extracted data for bias assessment and meta-analysis of bleeding, further intervention, mortality, transfusion, and intensive care unit admission. Available data were pooled using a random-effects model, and the results were presented as risk ratios (RRs) with 95% confidence intervals (CIs). Heterogeneity and small study effects were also assessed. RESULTS Thirteen randomized controlled trials (n = 2271) were included in the present synthesis. Our meta-analysis revealed that tranexamic acid significantly reduced the rates of continued bleeding (RR = 0.60; 95%CI, 0.43-0.84), urgent endoscopic intervention (RR = 0.35; 95%CI, 0.24-0.50), and mortality (RR = 0.60; 95%CI, 0.45-0.80) compared with the placebo. CONCLUSION According to the available evidence, the present synthesis confirms that tranexamic acid is an effective medication for patients with upper gastrointestinal bleeding. Early administration of tranexamic acid may be worth to be recommended for treating upper gastrointestinal bleeding in the emergency department. However, the effects of tranexamic acid on lower gastrointestinal bleeding warrant further clarification.
Tranexamic acid in the management of upper gastrointestinal bleeding: an evidence-based case report
Acta Medica Indonesiana. 2015;47((2)):172-5.
AIM: to review the effectiveness of tranexamic acid therapy which has been proposed to reduce bleeding and in turn lower mortality rate. METHODS following literature searching based on our clinical question on Cochrane Library, PubMed, Clinical Key, EBSCO, Science Direct and Proquest, one systematic review that includes seven randomized controlled trials is obtained. The article meets validity and relevance criteria. RESULTS the systematic review found that there is no any clear evidence between intervention and control groups in term of mortality. CONCLUSION the use of tranexamic acid to reduce mortality in patients with upper gastrointestinal bleeding is not recommended.
Tranexamic acid for upper gastrointestinal bleeding
Cochrane Database of Systematic Reviews. 2014;11:CD006640.
Background Tranexamic acid reduces haemorrhage through its antifibrinolytic effects. In a previous version of the present review, we found that tranexamic acid may reduce mortality. This review includes updated searches and new trials.Objectives To assess the effects of tranexamic acid versus no intervention, placebo or other antiulcer drugs for upper gastrointestinal bleeding.Search methods We updated the review by performing electronic database searches (Cochrane Central Register of Controlled Trials (CENTRAL),MEDLINE, EMBASE, Science Citation Index) and manual searches in July 2014.Selection criteriaRandomised controlled trials, irrespective of language or publication status.Data collection and analysis We used the standard methodological procedures of the The Cochrane Collaboration. All-cause mortality, bleeding and adverse events were the primary outcome measures. We performed fixed-effect and random-effects model meta-analyses and presented results as risk ratios (RRs) with 95% confidence intervals (CIs) and used I2 as a measure of between-trial heterogeneity. We analysed tranexamic acid versus placebo or no intervention and tranexamic acid versus antiulcer drugs separately. To analyse sources of heterogeneity and robustness of the overall results, we performed subgroup, sensitivity and sequential analyses.Main results We included eight randomised controlled trials on tranexamic acid for upper gastrointestinal bleeding. Additionally, we identified one large ongoing pragmatic randomised controlled trial from which data are not yet available. Control groups were randomly assigned to placebo (seven trials) or no intervention (one trial). Two trials also included a control group randomly assigned to antiulcer drugs(lansoprazole or cimetidine). The included studies were published from 1973 to 2011. The number of participants randomly assigned ranged from 47 to 216 (median 204). All trials reported mortality. In total, 42 of 851 participants randomly assigned to tranexamic acid and 71 of 850 in the control group died (RR 0.60, 95% CI 0.42 to 0.87; P value 0.007; I2 = 0%). The analysis was not confirmed when all participants in the intervention group with missing outcome data were included as treatment failures, or when the analysis was limited to trials with low risk of attrition bias. Rebleeding was diagnosed for 117 of 826 participants in the tranexamic acid group and for 146 of 825 participants in the control group (RR 0.80, 95% CI 0.64 to 1.00; P value 0.07; I2 = 49%).We were able to evaluate the risk of serious adverse events on the basis of only four trials. Our analyses showed 'no evidence of a difference between tranexamic acid and control interventions regarding the risk of thromboembolic events.' Tranexamic acid appeared to reduce the risk of surgery ina fixed-effect meta-analysis (RR 0.73, 95% CI 0.56 to 0.95), but this result was no longer statistically significant in a random-effects meta-analysis (RR 0.61, 95% CI 0.35 to 1.04; P value 0.07). No difference was apparent between tranexamic acid and placebo in the assessment of transfusion (RR 1.02, 95% CI 0.94 to 1.11; I2 = 0%), and meta-analyses that compared tranexamic acid versus antiulcer drugs did not identify beneficial or detrimental effects of tranexamic acid for any of the outcomes assessed.Authors' conclusions This review found that tranexamic acid appears to have a beneficial effect on mortality, but a high dropout rate in some trials means that we cannot be sure of this until the findings of additional research are published. At the time of this update in 2014, one large study(8000 participants) is in progress, so this review will be much more informative in a few years. Further examination of tranexamic acid would require inclusion of high-quality randomised controlled trials. Timing of randomisation is essential to avoid attrition bias and to limit the number of withdrawals. Future trials may use a pragmatic design and should include all participants with suspected bleeding or with endoscopically verified bleeding, as well as a tranexamic pla
Systematic review: tranexamic acid for upper gastrointestinal bleeding
Alimentary Pharmacology & Therapeutics. 2008;27((9):):752-8.
BACKGROUND Tranexamic acid may reduce upper gastrointestinal bleeding and stabilize patients before endoscopic treatments. AIM: To review randomized trials on tranexamic acid for upper gastrointestinal bleeding. METHODS Manual and electronic searches of The Cochrane Library, MEDLINE, EMBASE and Science Citation Index were combined. Intention-to-treat random effect meta-analyses were performed and results presented as RRs with 95% confidence intervals. RESULTS Seven double-blind randomized trials on tranexamic acid vs. placebo were included. Of 1754 patients randomized, 21% were excluded. Only one trial included endoscopic treatments or proton pump inhibitors. Five per cent of patients on tranexamic acid and 8% of controls died (RR: 0.61, 95% CI: 0.42-0.89). No significant differences were found on bleeding, bleeding-related mortality, surgery or transfusion requirements. Adverse events were unclearly reported. Data from three of the included trials suggested that tranexamic acid did not significantly increase the risk of thromboembolic disease. CONCLUSIONS The present review suggests that tranexamic acid may reduce all-cause mortality. However, because of limitations in the internal and external validity of included trials, additional evidence is needed before treatment recommendations can be made.
Effects of fibrinolytic inhibitors on mortality from upper gastrointestinal haemorrhage
OBJECTIVE To see whether fibrinolytic inhibitors are of value when given to patients with upper gastrointestinal haemorrhage. DESIGN Meta-analysis of six randomised double blind placebo controlled trials. Two methods used for obtaining an overall estimate of effect, including a random effects model incorporating any heterogeneity of outcome in the estimate of the overall treatment effect. SETTING Inpatient care in hospitals in the United Kingdom, Sweden, and Australia. PATIENTS 1267 Patients admitted to hospital with primary diagnosis of acute upper gastrointestinal haemorrhage. Five of the six trials included a high proportion of elderly patients. Most patients were bleeding from peptic ulcers in the stomach and duodenum (43-88%) or gastric erosions (4-23%). A variable proportion had a degree of clinical shock at entry. INTERVENTIONS Tranexamic acid 3-6 g/day given intravenously for two or three days followed by 3-6 g/day by mouth for a further three to five days (four trials) or 4. 5-12 g/day by mouth for two to seven days (two trials). END POINTS Frequency of recurrent haemorrhage, need for surgery, and death. MAIN RESULTS Treatment with tranexamic acid was associated with a 20-30% reduction in the rate of rebleeding, a 30-40% reduction (95% confidence interval 10% to 60%) in mortality. CONCLUSIONS Treatment with tranexamic acid may be of value to patients considered to be at risk of dying after an upper gastrointestinal haemorrhage.