In adults with severe acute GI bleeding, tranexamic acid did not reduce death due to bleeding at 5 days
Based on findings from a randomized trial, tranexamic acid is unlikely to confer additional benefit beyond the current standard of care in all patients with severe upper or lower GI bleeding, an ACP Journal Club commentary said.
The HALT-IT (Hemorrhage Alleviation With Tranexamic Acid-Intestinal System) randomized trial assessed whether tranexamic acid reduces mortality compared with placebo in adults with severe acute GI bleeding. The trial included 12,009 adults (mean age, 58 years; 64% men) who had clinically significant acute upper or lower GI bleeding in 164 hospitals in 15 countries. Participants received either tranexamic acid (1-g loading dose infused over 10 min, then 3-g maintenance dose infused at 125 mg/h for 24 h) or placebo (0.9% sodium chloride). Death due to bleeding within five days of randomization was not different between groups, occurring in 222 (4%) of 5,956 patients in the tranexamic acid group and in 226 (4%) of 5,981 patients in the placebo group (risk ratio, 0.99; 95% CI, 0.82 to 1.18).
The study was published June 20 by The Lancet. The following commentary, by ACP Member Laura C. Horton, MD, and Joseph D. Feuerstein, MD, appeared in the ACP Journal Club section of the Oct. 20 Annals of Internal Medicine.
The benefit of tranexamic acid in non-GI severe bleeding may be most pronounced when the drug is given immediately after bleeding onset, which may be difficult to ascertain in GI bleeding. A previous meta-analysis of tranexamic acid vs. placebo in patients with upper GI bleeding found the drug reduced mortality but not rebleeding/continued bleeding, surgery, or transfusion requirements. It did not show a mortality benefit compared with antiulcer drugs. The external validity of the included trials was limited as most were done between 1973 and 2001 when standard of care did not generally include endoscopic therapy. Attrition bias was also an important concern. Tranexamic acid benefit has not been shown in lower GI bleeding.
The well-designed HALT-IT trial found no mortality benefit with tranexamic acid vs. placebo in a [heterogeneous] population of patients with upper or lower GI bleeding. The trial's strengths included low dropout rate and improved external validity compared with previous studies. Its limitations included poorly defined inclusion criteria (e.g., risk for bleeding to death not well defined) and risk for type I (“false positive”) error (14 adverse events evaluated without adjustment for multiple analyses). Tranexamic acid increased venous thrombotic events and seizures compared with placebo; however, the clinical importance of these results is unclear in the setting of life-threatening bleeding. Lack of a mortality benefit in HALT-IT may reflect changes in the standard of care, which now includes antiulcer drugs and, often, endoscopic therapy.
Based on the HALT-IT findings, tranexamic acid is unlikely to confer additional benefit beyond the current standard of care in all patients with severe upper or lower GI bleeding. In select cases, such as patients with ongoing, severe GI bleeding that is refractory to antiulcer drugs and endoscopic therapy, a trial of tranexamic acid may be considered following a risk–benefit assessment.