Key Points:
- Tranexamic acid, given to patients undergoing noncardiac surgery, was associated with fewer bleeding events at 30 days.
- Participants of the POISE-3, a multinational, double-blinded randomized control study, were randomized to receive IV tranexamic acid or placebo during surgery.
- Study investigators conclude that the drug, already in widespread use for cardiac surgery, could have major economical and public health impact if used in the noncardiac space.
A single dose of tranexamic acid (TXA) given at the beginning and end of surgery has been shown to significantly decrease bleeding. The promising results of the generic drug, which promotes blood clotting, were revealed at the American College of Cardiology’s 71st Annual Scientific Sessions during a late-breaking clinical trial session.
Perioperative bleeding is a common complication in patients undergoing noncardiac surgery, and at a time when blood is in short supply, surgery still accounts for 40% of all blood transfusions. TXA, which has already been shown to prevent clinically significant bleeding in heart surgery and trauma, was yet to have been tested in those undergoing noncardiac surgery. There lay the premise, therefore, for the Perioperative Ischemic Evaluation 3 (POISE-3) study. The multinational, randomized control trial enrolled 9,535 participants. Those included were at least 45 years of age and scheduled for noncardiac surgery with at least one risk factor for post-surgical bleeding and/or vascular complication (age >70 years, atherosclerosis, or undergoing major surgery, and impaired kidney function). Patients undergoing intracranial surgery and those with advanced kidney disease (GFR<30) were excluded from enrollment.
The average age at enrollment was 70, and participants were mostly male (56%). Patients were randomly assigned one dose of intravenous TXA or placebo at the beginning of surgery, and a second dose at the end. Participants, physicians, and all those directly involved in the study were blinded to treatment administered.
The primary efficacy outcome, a composite of life threatening, major, and critical organ bleeding, was assessed. At 30 days, those in the TXA group had significantly fewer events than those in the placebo arm (9.1 vs 11.7%, HR 0.76 [95% CI 0.67-0.87, p<0.0001]). This treatment effect was observed across all prespecified subgroups: orthopaedic vs. nonorthopaedic surgery; low vs. normal baseline hemoglobin; baseline NT-proBNP values; and baseline kidney function. There was no difference in the composite vascular outcome, including minor cardiovascular events, stroke, and peripheral venous thromboembolism, but the treatment did not meet its prespecified margin for safety, which was noted as a limitation of the study.
The authors concluded that standard use of TXA in noncardiac surgery could avoid over 8 million bleeding events resulting in transfusion per year. During his presentation, Dr. PJ Devereaux (MacMaster University, Hamilton, Canada) stated “widespread use of the drug would be economical, as it would benefit not only patients with risk factors for bleeding, but those who may bleed from unexpected surgical mishaps”. Dr. Michael Mack (Baylor Scotte and White Plano, TX) agreed, stating that the drug is already widely used in the field of cardiac surgery, but had reservations as to the ability of the study to promote generalized uptake in its use.
The results were simultaneously published in the New England Journal of Medicine.