加拿大汉密尔顿综合医院P.J. Devereaux团队研究了在接受非心脏手术的患者中使用氨甲环酸对出血结局的影响。2022年4月2日出版的《新英格兰医学杂志》发表了这项成果。

围手术期出血在接受非心脏手术的患者中很常见。氨甲环酸是一种抗纤维蛋白溶解药物，可以安全地减少此类出血。

研究组进行了一项涉及接受非心脏手术患者的试验。将患者随机分配，分别在手术开始和结束时接受氨甲环酸（1 g静脉推注）或安慰剂（本文报道），并使用部分析因设计，采用预防低血压或高血压的策略（本文未报道）。主要疗效结局为30天时危及生命的出血、大出血或严重器官出血（综合出血结局）。

主要安全性结局为30天时非心脏手术后心肌损伤、非出血性卒中、外周动脉血栓形成或症状性近端静脉血栓栓塞（综合心血管结局）。为了确定氨甲环酸在综合心血管结局方面不劣于安慰剂，危险比的单侧97.5%置信区间的上限必须低于1.125，单侧P值必须小于0.025。

共有9535名患者接受了随机分组。氨甲环酸组4757名患者中有433名（9.1%）发生综合出血结局事件，安慰剂组4778名患者中有561名（11.7%），危险比为0.76，组间差异显著。氨甲环酸组4581名患者中有649名（14.2%）发生综合心血管结局事件，安慰剂组4601名患者中有639名（13.9%），危险比为1.02。

研究结果表明，在接受非心脏手术的患者中，氨甲环酸组的综合出血发生率显著低于安慰剂组。虽然组间综合心血管结局的差异很小，但氨甲环酸的非劣效性尚未确定。

附：英文原文

Title: Tranexamic Acid in Patients Undergoing Noncardiac Surgery | NEJM

Author: P.J. Devereaux, M.D., Ph.D.,, Maura Marcucci, M.D.,, Thomas W. Painter, M.B., Ch.B.,, David Conen, M.D., M.P.H.,, Vladimir Lomivorotov, M.D.,, Daniel I. Sessler, M.D.,, Matthew T.V. Chan, M.B., B.S., Ph.D.,, Flavia K. Borges, M.D., Ph.D.,, María J. Martínez-Zapata, M.D., Ph.D.,, Chew-Yin Wang, M.B., Ch.B.,, Denis Xavier, M.D.,, Sandra N. Ofori, F.W.A.C.P.,, Michael K. Wang, M.D.,, Sergey Efremov, M.D., Ph.D.,, Giovanni Landoni, M.D.,, Ydo V. Kleinlugtenbelt, M.D., Ph.D.,, Wojciech Szczeklik, M.D., Ph.D.,, Denis Schmartz, M.D.,, Amit X. Garg, M.D., Ph.D.,, Timothy G. Short, M.B., Ch.B., M.D.,, Maria Wittmann, M.D.,, Christian S. Meyhoff, M.D., Ph.D.,, Mohammed Amir, F.R.C.S.Ed.,, David Torres, M.D.,, Ameen Patel, M.D., M.A.C.P.,, Emmanuelle Duceppe, M.D., Ph.D.,, Kurt Ruetzler, M.D., Ph.D.,, Joel L. Parlow, M.D.,, Vikas Tandon, M.D.,, Edith Fleischmann, M.D.,, Carisi A. Polanczyk, M.D., Sc.D.,, Andre Lamy, M.D.,, Sergey V. Astrakov, M.D., Ph.D.,, Mangala Rao, M.D.,, William K.K. Wu, Ph.D.,, Keyur Bhatt, M.S.,, Miriam de Nadal, M.D., Ph.D.,, Valery V. Likhvantsev, M.D.,, Pilar Paniagua, M.D., Ph.D.,, Hector J. Aguado, M.D., Ph.D.,, Richard P. Whitlock, M.D., Ph.D.,, Michael H. McGillion, R.N., Ph.D.,, Michael Prystajecky, M.D.,, Jessica Vincent, M.Sc.,, John Eikelboom, M.B., B.S.,, Ingrid Copland,, Kumar Balasubramanian, M.Sc.,, Alparslan Turan, M.D.,, Shrikant I. Bangdiwala, Ph.D.,, David Stillo, M.A.Sc.,, Peter L. Gross, M.D.,, Teresa Cafaro, M.D.,, Pascal Alfonsi, M.D., Ph.D.,, Pavel S. Roshanov, M.D.,, Emilie P. Belley-Cté, M.D., Ph.D.,, Jessica Spence, M.D., Ph.D.,, Toby Richards, M.D.,, Tomas VanHelder, M.D., Ph.D.,, William McIntyre, M.D., Ph.D.,, Gordon Guyatt, M.D.,, Salim Yusuf, M.D., D.Phil.,, and Kate Leslie, M.D.

Issue&Volume: 2022-04-02

Abstract:

Background

Perioperative bleeding is common in patients undergoing noncardiac surgery. Tranexamic acid is an antifibrinolytic drug that may safely decrease such bleeding.

Methods

We conducted a trial involving patients undergoing noncardiac surgery. Patients were randomly assigned to receive tranexamic acid (1-g intravenous bolus) or placebo at the start and end of surgery (reported here) and, with the use of a partial factorial design, a hypotension-avoidance or hypertension-avoidance strategy (not reported here). The primary efficacy outcome was life-threatening bleeding, major bleeding, or bleeding into a critical organ (composite bleeding outcome) at 30 days. The primary safety outcome was myocardial injury after noncardiac surgery, nonhemorrhagic stroke, peripheral arterial thrombosis, or symptomatic proximal venous thromboembolism (composite cardiovascular outcome) at 30 days. To establish the noninferiority of tranexamic acid to placebo for the composite cardiovascular outcome, the upper boundary of the one-sided 97.5% confidence interval for the hazard ratio had to be below 1.125, and the one-sided P value had to be less than 0.025.

Results

A total of 9535 patients underwent randomization. A composite bleeding outcome event occurred in 433 of 4757 patients (9.1%) in the tranexamic acid group and in 561 of 4778 patients (11.7%) in the placebo group (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). A composite cardiovascular outcome event occurred in 649 of 4581 patients (14.2%) in the tranexamic acid group and in 639 of 4601 patients (13.9%) in the placebo group (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).

Conclusions

Among patients undergoing noncardiac surgery, the incidence of the composite bleeding outcome was significantly lower with tranexamic acid than with placebo. Although the between-group difference in the composite cardiovascular outcome was small, the noninferiority of tranexamic acid was not established.

DOI: 10.1056/NEJMoa2201171

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2201171