Tranexamic acid POISEd for wider use in noncardiac surgery

Using the antifibrinolytic tranexamic acid (TXA) during noncardiac surgery significantly reduces bleeding without significant increases in vascular complications in patients at risk for these complications, according to the POISE-3* trial presented at ACC 2022.

“We saw an unequivocal benefit of treatment [with TXA] on preventing bleeding and blood transfusions, with no increased risk of complications,” said lead author Professor Philip J Devereaux of McMaster University in Hamilton, Canada.

While perioperative bleeding is common in noncardiac surgery, majority of patients undergoing such surgery do not receive TXA, noted Devereaux. At a time when there is global shortage of blood product, surgery accounts for at least 40 percent of all blood transfusions, he pointed out.

“If we could safely prevent post-surgical bleeding and reduce the need for blood transfusions, it would be a huge contribution to global health,” Devereaux said. “Given that 300 million surgeries occur annually worldwide, [the] use of TXA could avoid upwards of 8 million bleeding events resulting in transfusion on [an] annual basis.”

Clear benefit

In the international trial with a partial 2X2 factorial design, 9,535 patients (mean age 70 years, 56 percent male) who were scheduled for noncardiac surgery and who had elevated risk of post-surgical bleeding and vascular events were randomized to receive an intravenous bolus of TXA (1 g) or placebo at surgery start and another dose at the end of surgery. [N Engl J Med 2022;doi:10.1056/NEJMoa2201171]

The primary composite efficacy outcome — comprising life-threatening bleeding, major bleeding, or bleeding into a critical organ — was significantly reduced in patients who received TXA compared with those on placebo (9.1 percent vs 11.7 percent; absolute difference, −2.6 percentage points; hazard ratio [HR], 0.76; p<0.001 for superiority).

Individual components of the composite bleeding outcome were also lower.

Moreover, TXA was associated with significantly lower rates of ISTH** major bleeding (6.6 percent vs 8.7 percent; p=0.0001) and reduced need for blood transfusion (in terms of ≥1 units of packed red blood cells) (9.4 percent vs 12.0 percent; p<0.0001).

There was no significant increase in the composite cardiovascular outcome***, which occurred in 14.2 percent of the patients given TXA compared with 13.9 percent in the placebo group (HR, 1.02; absolute difference, 0.3 percentage points; one-sided p=0.04 for noninferiority).

Although noninferiority was not established, the probability of increased vascular risk was low, stated Devereaux, who noted the absolute difference was 0.3 percentage points between the two groups.

“Healthcare providers and patients will have to weigh a clear beneficial reduction in the incidence of composite bleeding outcome events against the low probability of a small increase in the incidence of composite cardiovascular outcome events,” Devereaux advised.

In addition, the benefit of TXA was seen regardless of whether it was orthopaedic and nonorthopaedic surgery — across vascular, spinal, thoracic, urology, or gynaecology surgeries.

“Because the drug is so cheap, we can apply it to a broad population, even at an economic level, it looks like it is a winner to give to almost all patients having major noncardiac surgery,” Devereaux pointed out, noting that TXA is mainly confined to orthopaedic surgery in current practice.

“The POISE-3 trial indicates the potential for large public health and clinical benefits if TXA becomes standard practice in noncardiac surgery,” he stated.

*POISE-3: Perioperative Ischemic Evaluation–3

**ISTH: International Society on Thrombosis and Haemostasis

***myocardial injury after noncardiac surgery (MINS), nonhemorrhagic stroke, peripheral arterial thrombosis, and symptomatic proximal venous thromboembolism (VTE)