Effect of High- vs Low-Dose Tranexamic Acid Infusion on Need for Red Blood Cell Transfusion and Adverse Events in Patients Undergoing Cardiac Surgery

Author:

Shi Jia1,Zhou Chenghui1,Pan Wei2,Sun Hansong3,Liu Sheng3,Feng Wei3,Wang Weijian4,Cheng Zhaoyun5,Wang Yang6,Zheng Zhe37,Wang Liqing8,Song Yunhu8,Yu Chuntao8,Wang Xin8,Wang Xianqiang8,Fan Hongguang8,Yang Yan8,Xu Fei8,Gao Ge8,Zhang Yan8,Li Haojie8,Li Wei8,Li Jing8,Yan Fuxia8,Yuan Su8,Zhao Yan8,Zhang Yue8,Ji Bingyang8,Zhang Heng8,Liu Jiamin8,Ma Yan8,Du Juan8,Chen Zujun8,Shi Li8,Fan Yuxiu8,Lin Hongqi8,Wang Taofu8,Lu Ting8,Dai Zheng8,Xie Chunmei8,

Affiliation:

1. Department of Anesthesiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

2. Department of Anesthesiology, Baylor College of Medicine and Texas Heart Institute, Houston

3. Department of Cardiovascular Surgery, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

4. Department of Anesthesiology, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China

5. Department of Cardiovascular Surgery, Henan Province People’s Hospital, Fuwai Central China Cardiovascular Hospital, Henan Cardiovascular Hospital and Zhengzhou University, Zhengzhou, China

6. Department of Medical Research and Biometrics Center, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

7. National Health Commission Key Laboratory of Cardiovascular Regenerative Medicine, Fuwai Central China Hospital, Central China Branch of National Center for Cardiovascular Diseases, Zhengzhou, China

8. for the OPTIMAL Study Group

Abstract

ImportanceTranexamic acid is recommended for reducing blood loss and transfusion in cardiac surgery. However, it remains unknown whether a high dose of tranexamic acid provides better blood-sparing effect than a low dose without increasing the risk of thrombotic complications or seizures in cardiac surgery.ObjectiveTo compare the efficacy and adverse events of high-dose vs low-dose tranexamic acid in patients undergoing cardiac surgery with cardiopulmonary bypass.Design, Setting, and ParticipantsMulticenter, double-blind, randomized clinical trial among adult patients undergoing cardiac surgery with cardiopulmonary bypass. The study enrolled 3079 patients at 4 hospitals in China from December 26, 2018, to April 21, 2021; final follow-up was on May 21, 2021.InterventionsParticipants received either a high-dose tranexamic acid regimen comprising a 30-mg/kg bolus, a 16-mg/kg/h maintenance dose, and a 2-mg/kg prime (n = 1525) or a low-dose regimen comprising a 10-mg/kg bolus, a 2-mg/kg/h maintenance dose, and a 1-mg/kg prime (n = 1506).Main Outcomes and MeasuresThe primary efficacy end point was the rate of allogeneic red blood cell transfusion after start of operation (superiority hypothesis), and the primary safety end point was a composite of the 30-day postoperative rate of mortality, seizure, kidney dysfunction (stage 2 or 3 Kidney Disease: Improving Global Outcomes [KDIGO] criteria), and thrombotic events (myocardial infarction, ischemic stroke, deep vein thrombosis, and pulmonary embolism) (noninferiority hypothesis with a margin of 5%). There were 15 secondary end points, including the individual components of the primary safety end point.ResultsAmong 3079 patients who were randomized to treatment groups (mean age, 52.8 years; 38.1% women), 3031 (98.4%) completed the trial. Allogeneic red blood cell transfusion occurred in 333 of 1525 patients (21.8%) in the high-dose group and 391 of 1506 patients (26.0%) in the low-dose group (risk difference [RD], −4.1% [1-sided 97.55% CI, −∞ to −1.1%]; relative risk, 0.84 [1-sided 97.55% CI, −∞ to 0.96; P = .004]). The composite of postoperative seizure, thrombotic events, kidney dysfunction, and death occurred in 265 patients in the high-dose group (17.6%) and 249 patients in the low-dose group (16.8%) (RD, 0.8%; 1-sided 97.55% CI, −∞ to 3.9%; P = .003 for noninferiority). Fourteen of the 15 prespecified secondary end points were not significantly different between groups, including seizure, which occurred in 15 patients (1.0%) in the high-dose group and 6 patients (0.4%) in the low-dose group (RD, 0.6%; 95% CI, −0.0% to 1.2%; P = .05).Conclusions and RelevanceAmong patients who underwent cardiac surgery with cardiopulmonary bypass, high-dose compared with low-dose tranexamic acid infusion resulted in a modest statistically significant reduction in the proportion of patients who received allogeneic red blood cell transfusion and met criteria for noninferiority with respect to a composite primary safety end point consisting of 30-day mortality, seizure, kidney dysfunction, and thrombotic events.Trial RegistrationClinicalTrials.gov Identifier: NCT03782350

Publisher

American Medical Association (AMA)

Subject

General Medicine

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