Shi J, et al. JAMA. 2022;doi:10.1001/jama.2022.10725.

Shi J, et al. JAMA. 2022;doi:10.1001/jama.2022.10725.

Among patients undergoing elective CABG, infusion of high-dose tranexamic acid modestly reduced the need for red blood cell transfusion and was noninferior to low-dose infusion regarding safety, findings show.

The results of the OPTIMAL trial were published in JAMA.

“This trial extends previous findings by showing that in patients undergoing cardiac surgery, high and low doses of continuously infused tranexamic acid were associated with similar adverse event rates, but the high dose was more efficacious than the low dose with regard to reducing need for red blood cell transfusion, and high-dose tranexamic acid had a superior antifibrinolytic effect as indicated by postoperative plasma D-dimer levels,” Jia Shi, MD, of the department of anesthesiology in the State Key Laboratory of Cardiovascular Disease at Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College in Beijing, and colleagues wrote. “The current study is the only large-scale randomized trial, to our knowledge, to examine the dose-dependent clinical and adverse effects of continuous infusion of tranexamic acid in cardiac surgery patients.”

To evaluate the efficacy and safety of high-dose compared with low-dose tranexamic acid in patients undergoing elective CABG, Shi and colleagues conducted the multicenter, double-blind, randomized OPTIMAL trial.

The researchers enrolled 3,079 patients at four hospitals in China (mean age, 53 years; 38% women) who were randomly assigned to a high-dose tranexamic acid regimen (30 mg/kg bolus; 16 mg/kg/hour maintenance dose; and a 2 mg/kg prime) or a low-dose regimen (10 mg/kg bolus; 2 mg/kg/hour maintenance dose; and a 1 mg/kg prime).

The primary efficacy endpoint was rate of allogeneic red blood cell transfusion after start of operation. The primary safety endpoint was a composite of 30-day postoperative mortality, seizure, kidney dysfunction and thrombotic events, such as MI, ischemic stroke, deep vein thrombosis and pulmonary embolism.

Among participants undergoing CABG who completed the trial (98.4%), red blood cell transfusion occurred in 21.8% of the high-dose group and 26% of the low-dose group with a risk difference of 4.1% in the high-dose cohort (1-sided 97.55% CI, negative infinity to 1.1%; RR = 0.84; 1-sided 97.55% CI, negative infinity to 0.96; P = .004).

Moreover, the composite primary safety endpoint occurred in 17.6% of the high-dose cohort and 16.8% of the low-dose cohort, with a risk difference of 0.8% indicating the noninferiority of high-dose tranexamic acid compared with low-dose during CABG (1-sided 97.55% CI, negative infinity to 3.9%; P for noninferiority = .003).

Researchers reported no significant difference between high- and low-dose groups for median length of mechanical ventilation, ICU length of stay or postoperative hospital length of stay nor the secondary outcomes of 30-day risk for MI and incidences of kidney dysfunction, ischemic stroke, PE, DVT and seizures.

“The trial is limited to the Chinese population,” the researchers wrote. “Caution should be used in applying these findings to other ethnic populations.”

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