Study Design Summary: Multicenter, international placebo controlled trial of roughly 12,000 patients who were given TXA, primary outcome of death due to bleeding at 5 days.
Notes: They used a slightly higher maintenance dose of (3g vs the usual 1g over 8 hours) in patients who were deemed to have a significant risk of death from wither upper or lower GIB. Groups were well balanced in respect to average age, location of bleed (upper vs lower), blood pressure, signs of shock and comorbidities.
Primary outcome was death due to bleeding at 5 days, but they also collected data on death due to bleeding at 24 hours and 28 days as well as rebreeding at 24 hours, 5 days and 28 days. The TXA and placebo groups were identical in all aspects of these outcomes.
The rate of thromboembolic events was roughly similar to previous studies, arterial thromboembolic events such as MI or stroke were the same between TXA and placebo group in this study. The TXA group had slightly higher venous thromboembolic events in this study but it was not statistically significant. This trend was demonstrated in some previous studies but never reached statistical significance in any of them. The numbers were slightly higher in this TXA group and the authors offer this explanation, “Recent research shows that acutely ill patients with cirrhosis have a mixed fibrinolytic phenotype.17 Some have increased fibrinolysis, but others have profound hypo fibrinolysis. The prevalence of hypofibrinolysis appears to be greatest in the most critically ill patients. Using the same clot lysis assay, reduced fibrinolysis has been shown to be associated with a small increased risk of venous thrombosis.18 In our trial, the increased risk of venous thromboembolic events with tranexamic acid appeared to be more marked in patients with liver disease, although this was an exploratory subgroup analysis and there was no strong evidence for heterogeneity.”
“The dose of tranexamic acid used in this trial was higher and the duration of treatment was longer (4 g over 24 h) than in randomised trials of tranexamic acid in trauma (2 g over 8 h) or postpartum haemorrhage (1 g bolus with a repeat 1 g dose if bleeding continued), which did not record any increase in adverse events with tranexamic acid. Patients with gastrointestinal bleeding often rebleed after initial haemostasis, particularly within the first 24 h. Because tranexamic acid has a short halflife, we used a longer treatment duration to cover this highrisk period. Furthermore, previous trials in gastrointestinal bleeding that appeared to show a large mortality reduction with tranexamic acid used a high dose and a longer duration of treatment than trials in trauma and postpartum hemorrhage.”
Previous studies have shown that TXA is more effective if given within the first 3 hours since injury. The authors do a nice job of addressing this physiology question as to why this study did not show benefit to TXA administration, “the timing of onset is easy to determine, most patients present early, and there are well documented changes in fibrinolysis that provide a biological rationale for tranexamic acid treatment.15,16 However, in gastro intestinal bleeding it is difficult to determine the time of bleeding onset, presentation is often delayed (over 80% of patients presented more than 3 h after bleeding onset), and the contribution of increased fibrinolysis to bleeding is less clear.”
This was a well done study with sound logic as to why they chose a higher dose TXA. They didn’t spin their results to make it a positive study and offer sound logic as to why TXA is likely both ineffective in reducing GIB mortality and why VTE is slightly higher in TXA group. I believe the results are reliable and the you can rest your hat on these results.
Study Conclusion: TXA does not reduce the risk of death due to bleeding in GI bleed patients and should not be used outside of randomized controlled trials.
Fusion Beat Bottom Line Impression: The study demonstrates no decreased mortality to patients given TXA for GIB, and risk of VTE was slightly higher in TXA group but not statistically signifiant.
A Fusion Beat 