利伐沙班致非瓣膜性心房颤动合并冠心病患者相关出血事件的影响因素分析

陈铭瑜; 陈敏; 邓金珠; 戴强; 高红瑾

doi:10.6039/j.issn.1001-0408.2024.18.14

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利伐沙班致非瓣膜性心房颤动合并冠心病患者相关出血事件的影响因素分析

药物与临床 | 更新时间：2024-09-25

- 利伐沙班致非瓣膜性心房颤动合并冠心病患者相关出血事件的影响因素分析
- Analysis of influential factors for rivaroxaban-induced bleeding events in patients with non-valvular atrial fibrillation complicated with coronary heart disease
- 中国药房 2024年35卷第18期页码：2272-2277
- 作者机构：
  
  1.福建医科大学省立临床医学院/福州大学附属省立医院药学部，福州　350001
  2.福建医科大学药学院，福州　350122
- 作者简介：
  
  硕士研究生。研究方向：临床药学。E-mail：798446881@qq.com
  副主任药师，硕士生导师。研究方向：临床药学、心血管药理学。E-mail：gaohongjin777@fjmu.edu.cn
- 基金信息：
  
  福建省社会发展引导性（重点）项目(2023Y0045);福建医科大学大学生创新训练项目(C2024177)
- DOI：10.6039/j.issn.1001-0408.2024.18.14
  中图分类号： R973+.2
- 纸质出版日期：2024-09-30，
  
  收稿日期：2024-03-12，
  
  修回日期：2024-07-03，
- 稿件说明：
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陈铭瑜,陈敏,邓金珠等.利伐沙班致非瓣膜性心房颤动合并冠心病患者相关出血事件的影响因素分析 ^Δ[J].中国药房,2024,35(18):2272-2277.

CHEN Mingyu,CHEN Min,DENG Jinzhu,et al.Analysis of influential factors for rivaroxaban-induced bleeding events in patients with non-valvular atrial fibrillation complicated with coronary heart disease[J].ZHONGGUO YAOFANG,2024,35(18):2272-2277.
陈铭瑜,陈敏,邓金珠等.利伐沙班致非瓣膜性心房颤动合并冠心病患者相关出血事件的影响因素分析 ^Δ[J].中国药房,2024,35(18):2272-2277. DOI： 10.6039/j.issn.1001-0408.2024.18.14.

CHEN Mingyu,CHEN Min,DENG Jinzhu,et al.Analysis of influential factors for rivaroxaban-induced bleeding events in patients with non-valvular atrial fibrillation complicated with coronary heart disease[J].ZHONGGUO YAOFANG,2024,35(18):2272-2277. DOI： 10.6039/j.issn.1001-0408.2024.18.14.

摘要

目的

分析利伐沙班致非瓣膜性心房颤动（NVAF）合并冠心病患者相关出血事件的影响因素。

方法

回顾性收集福州大学附属省立医院心血管内科2021年11月－2023年5月使用利伐沙班进行抗凝治疗的NVAF合并冠心病住院患者64例，分析其人口统计学信息、实验室检查指标等一般临床资料及利伐沙班稳态血药浓度谷值，计算剂量调整谷浓度，并记录患者出院后6个月内相关出血事件的发生情况。采用单因素分析和二元Logistic回归分析确定利伐沙班相关出血事件的独立危险因素。构建预测出血概率的二元Logistic回归方程，采用受试者操作特征（ROC）曲线的曲线下面积（AUC）分析该回归方程的预测价值。

结果

64例患者中，共19例患者发生24例次出血事件，大多为轻度出血（19例次，79.2%），以胃肠道出血为主（17例次，70.8%），大多经对症处理、调整抗凝方案等处理后好转或痊愈。单因素分析结果显示，出血组既往有贫血史的患者比例、血小板计数、尿素氮

含量、利伐沙班稳态血药浓度谷值、利伐沙班剂量调整谷浓度和凝血指标[国际标准化比值、凝血酶原时间（PT）、活化部分凝血活酶时间

]

水平均显著多于或高于非出血组，而白蛋白水平显著低于非出血组（

＜0.05）。二元Logistics回归分析结果显示，高PT水平（比值比为1.473，95%置信区间为1.103～1.967，

＝0.009）和高利伐沙班剂量调整谷浓度（比值比为1.174，95%置信区间为1.018～1.355，

＝0.027）是利伐沙班相关出血事件的独立危险因素；出血事件预测概率（

）的二元Logistic回归方程为Logit

＝－6.975+0.387×PT水平+0.161×剂量调整谷浓度，其ROC曲线的AUC为0.825（95%置信区间为0.708～0.909，

＜0.001）。

结论

利伐沙班致NVAF合并冠心病患者相关出血事件的危险因素包括既往有贫血史、高血小板计数、高尿素氮含量、高利伐沙班稳态血药浓度谷值、高剂量调整谷浓度、高凝血指标水平以及低白蛋白水平，其中高PT水平和高剂量调整谷浓度是可用于预测利伐沙班相关出血事件发生风险的独立危险因素；所建回归方程具有较高的预测价值。

Abstract

OBJECTIVE

To analyze the influential factors for rivaroxaban-induced bleeding events in patients with non-valvular atrial fibrillation （NVAF） and coronary heart disease.

METHODS

A total of 64 hospitalized patients with NVAF complicated with coronary heart disease who were treated with rivaroxaban and admitted to the Fuzhou University Affiliated Provincial Hospital from November 2021 to May 2023 were included in this retrospective study. The demographic data， laboratory test indexes and other general clinical data， and steady-state trough concentration of rivaroxaban were collected， and the dose-adjusted trough concentration was calculated. The occurrence of bleeding events within 6 months after discharge was recorded. The univariate analysis and binary Logistic regression analysis were adopted to determine the independent risk factors of rivaroxaban-related bleeding events. The binary Logistic regression equation was constructed to predict the probability of bleeding events. The area under the receiver operator characteristic （ROC） curve （AUC） was used to analyze the predictive value of the regression equation.

RESULTS

Among 64 patients， 19 patients had 24 case-times bleeding events， most of which were mild bleeding （19 case-times，

79.2%）， and mainly gastrointestinal bleeding （17 case-times， 70.8%）. After symptomatic treatment and adjustment of the anticoagulant regimen， most of them were improved or cured. In the univariate analysis， the proportion of patients with a history of anemia， platelet count， urea nitrogen content， steady-state trough concentration of rivaroxaban， dose-adjusted trough concentration and coagulation indexes [international normalized ratio， prothrombin time （PT）， activated partial thromboplastin time

]

in bleeding group were significantly more or higher than those in non-bleeding group， while the albumin level was significantly lower than that in non-bleeding group （

＜0.05）. In binary Logistics regression analysis， high PT level （odds ratio＝1.473， 95% confidence interval＝1.103-1.967，

＝0.009） and high rivaroxaban dose-adjusted trough concentration （odds ratio＝1.174， 95% confidence interval＝1.018-1.355，

＝0.027） were independent risk factors for rivaroxaban-related bleeding events. The binary Logistic regression equation of bleeding event prediction probability （

） was Logit

＝－6.975+0.387×PT level+0.161×dose-adjusted trough concentration， and the AUC of the ROC curve was 0.825 （95% confidence interval was 0.708-0.909，

＜0.001）.

CONCLUSIONS

The risk factors of rivaroxaban-related bleeding events in patients with NVAF and coronary heart disease include previous anemia history， high platelet count， high urea nitrogen content， high rivaroxaban steady-state trough concentration， high dose-adjusted trough concentration， high coagulation indexes and low albumin level. High PT level and high dose-adjusted trough concentration are independent risk factors that can be used to predict the risk of rivaroxaban-induced bleeding events. The regression equation has good predictive value.

关键词

利伐沙班非瓣膜性心房颤动冠心病出血事件凝血酶原时间剂量调整谷浓度独立危险因素

Keywords

non-valvular atrial fibrillationcoronary heart diseasebleeding eventsprothrombin timedose-adjusted trough concentrationindependent risk factor

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