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POISE-3: Tranexamic Acid Can Reduce Bleeding Risk Without Increasing CV Risk in Noncardiac Surgery

Conference | <b>American College of Cardiology</b>

Data from POISE-3 presented at ACC.22 detail the effects of tranexamic acid on reducing the risk of major bleeding in patients undergoing noncardiac surgery.

Data from the POISE-3 trial suggest tranexamic acid could lower risk of serious bleeding without increasing risk of adverse cardiovascular events after noncardiac surgery.

Presented at the American College of Cardiology’s 71st Annual Scientific Session and simultaneously published in the New England Journal of Medicine, results of the study demonstrate use of tranexamic acid was associated with significant reduction in serious bleeding events and need for blood transfusion while a statistical analysis determined there was a more than 95% probability of safety compared to placebo therapy for comparisons of adverse events.

“We saw an unequivocal benefit of treatment [with TXA] on preventing bleeding and blood transfusions, with no increased risk of complications,” said lead investigator P.J. Devereaux, MD, PhD, director of the Division of Perioperative Care at McMaster University in Hamilton, Canada, in a statement. “Given the number of people worldwide who undergo noncardiac surgery every year and the frequency of postsurgical bleeding complications, this has the potential to help a lot of patients, and I hope it will lead to a substantial change in practice.”

With mechanistic studies demonstrating the potential for tranexamic acid, an antifibrinolytic, to reduce Perioperative bleeding risk, the Perioperative Ischemic Evaluation–3 (POISE-3) was designed as an international, randomized, controlled trial to assess the effects of tranexamic acid on risk of bleeding and for cardiovascular events among patients undergoing noncardiac surgery. With recruitment of patients occurring from June 2018-July 2021 in 114 hospitals across 22 countries, the trial enrolled patients aged 45 years or older who were undergoing noncardiac surgery and were at risk for bleeding and cardiovascular complications according to criteria previously associated with perioperative bleeding and cardiovascular complications.

Of note, criteria for being considered at risk were known ASCVD, undergoing major surgery, an age of 70 years or more, and a serum creatinine level above 175 μmol/l. Investigators pointed out patients were excluded if they were undergoing cardiac or intracranial neurosurgery, if a physician planned to administer systemic tranexamic acid during surgery, if the patient had a creatinine clearance of less than 30 ml per minute, or if they were receiving long-term dialysis.

Patients were randomized to receive 1g intravenous bolus of tranexamic acid or placebo at the start and end of surgery and, with the use of a partial factorial design, a hypotension-avoidance or hypertension-avoidance strategy. Investigators pointed out the results of the hypotension-avoidance or hypertension-avoidance strategy were not reported in the ACC.22 presentation or the NEJM article.

The primary efficacy outcome of interest for the study was a composite bleeding outcome of life-threatening bleeding, major bleeding, or bleeding into a critical organ at 30 days. The primary safety outcome of interest was a composite cardiovascular outcome of myocardial injury after noncardiac surgery, nonhemorrhagic stroke, peripheral arterial thrombosis, or symptomatic proximal venous thromboembolism at 30 days. In the interest of establishing noninferiority of tranexamic acid to placebo for the safety outcome, investigators determined the upper boundary of the one-sided 97.5% confidence interval for the hazard ratio had to be below 1.125, and the one-sided P-value had to be less than 0.025.

A total of 9535 patients underwent randomization in the study, with 4757 randomized to tranexamic acid and 4778 randomized to placebo therapy. The mean age of patients was 70 years, 56% were male, and 97% received both doses of assigned therapy. Investigators also noted 30-day follow-up was completed by more than 99% of participants.

Upon analysis, a composite bleed outcome event was identified among 9.1% (n=433) in the tranexamic group and 11.7% (n=561) in the placebo group (HR, 0.76 [95% CI, 0.67 to 0.87]; absolute difference, -2.6 percentage points [95% CI, -3.8 to -1.4]; two-sided P <.001 for superiority). When assessing safety, a composite safety outcome event was identified among 14.2% (n=649) in the tranexamic acid group and among 13.9% (n=639) in the placebo group (HR, 1.02 [95% CI, 0.92 to 1.14]; upper boundary of the one-sided 97.5% CI, 1.14; absolute difference, 0.3 percentage points [95% CI, −1.1 to 1.7]; one-sided P=.04 for noninferiority).

“We have a clear, robust result showing that we can safely reduce postsurgical bleeding by giving just two doses of a readily available drug immediately before and after noncardiac surgery,” Devereaux said. “Moreover, it’s a drug that we have a lot of experience with and in different settings, and it’s inexpensive.”

This study, “Tranexamic Acid in Patients Undergoing Noncardiac Surgery,” was presented at ACC.22 and simultaneously published in the New England Journal of Medicine.