Efficacy TXA will be superior to placebo for the composite bleeding outcome at 30 days
Safety: TXA will be noninferior to placebo for the composite cardiovascular outcome at 30 days
Methods
RCT
International, multicenter
9,535 subjects
Protocol: 1gm TXA bolus at beginning of surgery and 1gm TXA bolus at end of surgery
Outcomes
Composite bleeding outcome: life-threatening bleeding, major bleeding, or bleeding into a critical organ at 30 days.
Composite safety outcome: myocardial injury after noncardiac surgery, non-hemorrhagic stroke, peripheral arterial thrombosis, or symptomatic proximal venous thromboembolism at 30 days
Noninferiority margin
The upper limit of the 95% CI interval in the TXA group needs to show less than a 12.5% increase in incidence of the safety outcome
Results
TXA was superior to placebo for the composite bleeding outcome (TXA 9.1% vs. placebo 11.7%; hazard ratio, 0.76, 95% confidence interval [CI] 0.67 to 0.87; absolute difference -2.6 percentage points; 95% CI, -3.8 to -1.4; two-sided P<0.001 for superiority)
TXA was not found to be non-inferior to placebo for the composite safety outcome (TXA 14.2% vs. placebo 13.9%; hazard ratio, 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 = 0.04 for noninferiority)
Strengths
Large study
193,000 patients screened
9,535 patients randomized
Minimal # of patients lost to follow-up
22 countries with 114 sites
Appropriate analysis of the efficacy and safety outcomes
Superiority (efficacy) vs. non-inferiority (safety)
Weaknesses
Stopped trial slightly early
Low enrollment during COVID-19
Generalizability
Surgeries with lower bleeding risks
Key Point: TXA decreases the risk of bleeding during noncardiac surgery, but may increase the risk of cardiovascular complications