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High- vs. Low-Dose Tranexamic Acid for Cardiac Surgery
Quick Takes
- In patients undergoing cardiac surgery with cardiopulmonary bypass, use of a high-dose tranexamic acid infusion resulted in a modest but statistically significant decrease in need for red blood cell transfusions compared to a low-dose infusion.
- High-dose tranexamic acid infusion was not associated with a higher rate of adverse events including 30-day mortality, seizure, kidney dysfunction, and thrombotic events compared to a low-dose infusion.
Study Questions:
Is there a difference between low- and high-dose tranexamic acid on need for red blood cell transfusions and adverse events among patients undergoing cardiac surgery?
Methods:
Patients undergoing elective cardiopulmonary bypass (CPB) at four academic centers in China were randomized to receive either a high- or low-dose tranexamic acid dosing regimen. The high-dose group received an intravenous bolus of 30 mg/kg followed by a maintenance infusion of 16 mg/kg/hr throughout the surgery with a pump prime dose of 2 mg/kg. The low-dose group received a 10 mg/kg bolus dose and a 2 mg/kg/hr maintenance infusion with a 1 mg/kg pump prime dose. Participants, medical staff, and investigators were blinded to the treatment allocation. The primary endpoint was the need for any allogeneic red blood cell transfusion from the start of the surgery through hospital discharge. Thresholds for transfusion were set at a hemoglobin of 7 g/dL during CPB and 8 g/dL after CPB. The primary safety endpoint was a composite of postoperative seizure, stage 2 or 3 kidney dysfunction, thrombotic events, and all-cause mortality at 30 days. Additional endpoints included volume of red cell transfusion, postoperative bleeding volume, need for reoperation, duration of mechanical ventilation, and intensive care and hospital length of stay.
Results:
Of 3,079 patients randomized to treatment groups, 3,031 completed the trial (1,525 received high-dose tranexamic acid and 1,506 received a low-dose regimen). There were no significant differences in baseline characteristics between the groups including demographic and surgical characteristics. Red cell transfusion was required in 333 (21.8%) patients in the high-dose group compared to 391 (26.0%) in the low-dose group (relative risk, 0.84 [1-sided 97.55% CI, -∞ to 0.96, p = 0.004]). The composite of safety endpoints occurred in 265 (17.6%) patients in the high-dose group vs. 249 (16.8%) patients in the low-dose group (risk difference, 0.8%; 1-sided 97.55% CI, -∞ to 3.9%; p = 0.003 for noninferiority). There were no differences between groups among any of the safety composite components, including clinical seizures (1% high-dose vs. 0.4% low-dose, p = 0.05).
Conclusions:
Among patients undergoing cardiac surgery with CPB, a high-dose infusion of tranexamic acid was associated with a small but statistically significant reduction in the need for allogeneic red blood cell transfusion when compared to a low-dose infusion. The high-dose regimen was noninferior to the low-dose regimen with respect to a composite safety endpoint.
Perspective:
The findings of this trial provide additional support for tranexamic acid infusions administered during cardiac surgery by showing similar rates of adverse events between high- and low-dose infusions. The high-dose infusion was also more efficacious with regard to reducing the need for red blood cell transfusions. In a previous randomized controlled trial, the ATACAS trial, higher rates of seizures in patients receiving tranexamic acid 100 mg/kg as a single bolus led to a study dose amendment to 50 mg/kg during the enrollment period. Although the mean total dose of tranexamic acid in the high-dose group of this trial (mean 103.1 mg/kg) was similar to the initial dose used in ATACAS, the use of a continuous infusion likely resulted in different peak plasma tranexamic acid concentrations, which may have contributed to differences in adverse event rates between the trials.
Clinical Topics: Anticoagulation Management, Cardiac Surgery, Invasive Cardiovascular Angiography and Intervention, Prevention, Cardiac Surgery and Arrhythmias
Keywords: Acute Kidney Injury, Anticoagulants, Blood Transfusion, Cardiac Surgical Procedures, Cardiopulmonary Bypass, Critical Care, Erythrocyte Transfusion, Hemoglobins, Length of Stay, Patient Care Team, Patient Discharge, Reoperation, Respiration, Artificial, Risk, Secondary Prevention, Seizures, Thrombosis, Tranexamic Acid
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