Tranexamic acid and mortality in patients with acute GI bleeding
Tranexamic acid is an antifibrinolytic agent that promotes clotting in patients who are actively bleeding or who are at high risk for bleeding. It has been shown in large, well-designed randomized trials to reduce clinically overt bleeding, blood transfusion requirements, or both in patients who have posttraumatic or postpartum hemorrhage and in patients undergoing coronary artery bypass graft surgery without incurring an increased risk for arterial or venous thromboembolism. A meta-analysis of small trials suggested that tranexamic acid may reduce mortality in patients with gastrointestinal (GI) bleeding.
The HALT-IT trial was a multicenter, multinational randomized placebo-controlled trial that enrolled patients with life-threatening upper or lower GI bleeding. Patients were allocated to receive either intravenous tranexamic acid 1 g as a loading dose followed by a maintenance dose of tranexamic acid 3 g infused over 24 hours or intravenous placebo (sodium chloride). The primary study outcome was death due to GI bleeding within 5 days of randomization after excluding patients who received neither dose of treatment and those for whom outcome data on death were unavailable.
Over a 6-year period, 12,009 patients were recruited and randomly allocated to receive tranexamic acid (n = 5994) or matching placebo (n = 6015). Death due to GI bleeding within 5 days of randomization occurred in 222 (4%) of 5956 patients in the tranexamic acid group and in 226 (4%) of 5981 patients in the placebo group (risk ratio [RR], 0.99; 95% CI, 0.82-1.18). The rates of arterial thromboembolic events (myocardial infarction or stroke) were similar in the tranexamic acid group and the placebo group (0.7% vs 0.8%; RR, 0.92; CI, 0.60-1.39). The rates of venous thromboembolic events (deep vein thrombosis or pulmonary embolism) were higher in the tranexamic acid group than in the placebo group (0.8% vs 0.4%; RR, 1.85; 95% CI, 1.15-2.98). There were no patient subgroups in which tranexamic acid appeared to confer a therapeutic advantage. Venous thromboembolic events appeared to occur predominantly in patients with suspected variceal bleeding or liver disease.
The authors concluded that tranexamic acid should not be used for the treatment of GI bleeding outside the context of a randomized trial. Other randomized trials are investigating tranexamic acid in additional clinical settings, including the POISE-3 trial, which is assessing if its use reduces perioperative bleeding in patients undergoing elective noncardiac surgery.