June 20, 2020
Effects of a high-dose 24-h infusion of tranexamic acid on death and thromboembolic events in patients with acute gastrointestinal bleeding
What was the research question?
Does a high-dose 24-hour infusion of tranexamic acid reduce death and thromboembolic events in patients with acute gastrointestinal bleeding when compared to a placebo?
How did they do it?
An international, randomized, double-blind, placebo-controlled study conducted in 164 hospitals in 15 countries.
Adult patients with upper or lower gastrointestinal bleeding with risk of death.
Patients were randomized to receive either a loading dose of 1 g tranexamic acid in 100 mL infusion bag of 0·9% sodium chloride over 10 minutes, followed by a maintenance dose of 3 g tranexamic acid added to 1 L of any isotonic intravenous solution and infused at 125 mg/h for 24 h (5956 patients), or placebo with sodium chloride 0·9% (5981 patients).
The study's primary outcome was death from bleeding within 5 days of randomization, with secondary outcomes including death from bleeding within 24 hours and 28 days of randomization, all-cause and cause-specific mortality at 28 days, rebleeding within 24 hours, 5 days, and 28 days of randomization, surgery or radiological intervention, blood product transfusion, thromboembolic events, seizures, other complications, and days in an intensive care unit.
What did they find?
Death due to bleeding within 5 days of randomization occurred in 222 (3·7%) of 5956 patients in the tranexamic acid group and in 226 (3·8%) of 5981 patients in the placebo group (RR 0·99, 95% CI 0·82–1·18).
Arterial thromboembolic events (myocardial infarction or stroke) were similar in the tranexamic acid group and placebo group (42 [0·7%] of 5952 vs 46 [0·8%] of 5977; RR 0·92; 0·60 to 1·39).
Venous thromboembolic events (deep vein thrombosis or pulmonary embolism) were higher in tranexamic acid group than in the placebo group (48 [0·8%] of 5952 vs 26 [0·4%] of 5977; RR 1·85; 95% CI 1·15 to 2·98).
Seizures occurred in 38 patients on tranexamic acid and 22 on placebo (0·6% vs 0·4%; 1·73, 1·03–2·93).
Death due to bleeding within 24 hours and 28 days of randomization, as well as all-cause mortality within 28 days, were similar in both groups.
The proportion of patients with rebleeding, surgery, radiological intervention, and blood product transfusion was also similar in both groups.
What are the limitations?
The inability to evaluate the efficacy of tranexamic acid for particular patient subgroups and the exclusion of individuals with high-risk stigmata.
What does it mean?
The study suggests that a high-dose 24-hour infusion of tranexamic acid does not reduce death within 5 days of randomization in patients with acute gastrointestinal bleeding.
It cannot, however, rule out minor therapy effects. Individual patient data meta-analyses should be performed to determine the efficacy and safety of tranexamic acid based on the site and source of bleeding.