根据肾功能分层的冠状动脉造影或经皮冠状动脉介入治疗患者中减量比伐卢定的疗效与安全性（REDUCE BOLUS）：一项单盲、分层随机、非劣效性试验

Efficacy and Safety of the Reduced Bivalirudin in Patients Undergoing Coronary Angiography or Percutaneous Coronary Intervention Stratified by Renal Function (REDUCE BOLUS): A Single-Blind, Stratified Randomized, Non-inferiority Trial.

作者信息

Hu Qiang, Han Ya-Ling, Zhou Tie-Nan, Wang Xiao-Zeng, Zhang Quan-Yu

机构信息

Department of Cardiology, General Hospital of Northern Theater Command, Shenyang, China.

Department of Cardiology, Xijing Hospital, Air Force Medical University, Xi'an, China.

出版信息

Front Cardiovasc Med. 2022 Apr 25;9:864048. doi: 10.3389/fcvm.2022.864048. eCollection 2022.

BACKGROUND

In clinical practice, some cases indicated that the loading dose of bivalirudin increased the bleeding risk, particularly in patients with renal insufficiency. Therefore, this study aimed to assess the efficacy and safety of the low-dose (80%) bolus injection of bivalirudin in patients undergoing cardiac catheterization stratified by renal function.

METHODS

A total of 204 individuals in the REDUCE BOLUS trial were stratified 1:1 to the estimated glomerular filtration rate (eGFR) ≥ 60 ml/min cohort or eGFR < 60 ml/min cohort, then randomized 1:1 to the reduced bolus bivalirudin group (i.e., the experimental group) or normal bolus bivalirudin group (i.e., the control group), respectively. The primary end point was to compare the differences of the area under the curve of activated clotting time (ACT) between the two groups. The secondary end points were the postoperative net adverse clinical events (NACEs) before discharge, defined as the all-cause mortality, recurrent myocardial infarction, ischemia-driven target vessel revascularization, stroke, and bleeding events.

RESULTS

Between January 3, 2020, and March 26, 2021, 204 patients undergoing coronary angiography were randomly assigned, including 102 (i.e., 51 in the control group and 51 in the experimental group) with normal eGFR and 102 (i.e., 51 control and 51 experimental) with abnormal eGFR. No difference was observed in the curve of ACT between the control group and the experimental group (0.55 ± 0.09 vs. 0.56 ± 0.08, = 0.542 and 0.55 ± 0.06 vs. 0.57 ± 0.05, = 0.075, respectively, for normal eGFR cohort and abnormal eGFR cohort). The one-sided 97.5% lower confidence bound for the difference in the area under the ACT curve was -0.017 and 0.0015 in eGFR ≥ 60 ml/min and eGFR<60 ml/min cohort, respectively, both above the preset non-inferiority criterion of -0.07, establishing the non-inferiority. There was no incidence of NACE and stent thrombosis before discharge in each group.

CONCLUSION

In patients undergoing cardiac catheterization, the efficacy and safety of the reduced bolus of bivalirudin were non-inferior to the normal one, even in patients without chronic kidney disease.

CLINICAL TRIAL REGISTRATION

[www.ClinicalTrials.gov], identifier [NCT03588611].

背景

在临床实践中，一些病例表明比伐卢定的负荷剂量会增加出血风险，尤其是在肾功能不全的患者中。因此，本研究旨在评估按肾功能分层的接受心脏导管插入术患者中低剂量（80%）推注比伐卢定的疗效和安全性。

方法

REDUCE BOLUS试验中的204名个体按1:1比例分层至估计肾小球滤过率（eGFR）≥60 ml/min队列或eGFR<60 ml/min队列，然后分别按1:1比例随机分配至减量推注比伐卢定组（即试验组）或常规推注比伐卢定组（即对照组）。主要终点是比较两组活化凝血时间（ACT）曲线下面积的差异。次要终点是出院前术后净不良临床事件（NACEs），定义为全因死亡率、复发性心肌梗死、缺血驱动的靶血管血运重建、中风和出血事件。

结果

在2020年1月3日至2021年3月26日期间，204名接受冠状动脉造影的患者被随机分配，其中eGFR正常的有102名（即对照组51名，试验组51名），eGFR异常的有102名（即对照组51名，试验组51名）。对照组和试验组之间在ACT曲线上未观察到差异（eGFR正常队列中分别为0.55±0.09对0.56±0.08，P = 0.542；eGFR异常队列中分别为0.55±0.06对0.57±0.05，P = 0.075）。ACT曲线下面积差异的单侧97.5%置信下限在eGFR≥60 ml/min和eGFR<60 ml/min队列中分别为-0.017和0.0015，均高于预设的非劣效性标准-0.07，确立了非劣效性。每组出院前均无NACE和支架血栓形成事件发生。