合并稳定性冠状动脉疾病对非瓣膜性房颤患者单一抗凝治疗的潜在影响: 一项倾向性评分匹配研究

doi:10.5246/jcps.2025.11.074

中国药学(英文版) ›› 2025, Vol. 34 ›› Issue (11): 989-1002.DOI: 10.5246/jcps.2025.11.074

合并稳定性冠状动脉疾病对非瓣膜性房颤患者单一抗凝治疗的潜在影响: 一项倾向性评分匹配研究

陈铭瑜¹^,²^,^#, 黄有琪¹^,³^,^#, 邓金珠⁴, 林宇齐⁴, 高红瑾¹^,^*(), 陈敏¹^,^*()

^1. 福建医科大学省立临床医学院福建省立医院福州大学附属省立医院药学部, 福建福州 350001
^2. 福建医科大学附属第一医院药学部, 福建福州 350005
^3. 龙岩市药品检验检测中心, 福建龙岩 364000
^4. 福建医科大学药学院, 福建福州 350004

收稿日期:2025-07-18 修回日期:2025-08-20 接受日期:2025-09-11 出版日期:2025-12-02 发布日期:2025-12-02
通讯作者: 高红瑾, 陈敏

Impact of stable coronary artery disease on anticoagulation monotherapy in patients with nonvalvular atrial fibrillation: a propensity score-matched analysis

Mingyu Chen¹^,²^,^#, Youqi Huang¹^,³^,^#, Jinzhu Deng⁴, Yuqi Lin⁴, Hongjin Gao¹^,^*(), Min Chen¹^,^*()

¹ Department of Pharmacy, Shengli Clinical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital, Fuzhou 350001, Fujian, China
² Department of Pharmacy, the First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, Fujian, China
³ Longyan Pharmaceutical Inspection and Testing Center, Longyan 364000, Fujian, China
⁴ School of Pharmacy, Fujian Medical University, Fuzhou 350004, Fujian, China

Received:2025-07-18 Revised:2025-08-20 Accepted:2025-09-11 Online:2025-12-02 Published:2025-12-02
Contact: Hongjin Gao, Min Chen
About author:
^# Mingyu Chen and Youqi Huang contributed equally to this work.
Supported by:
The Guiding Projects issued by the Fujian Provincial Department of Science and Technology, China (Grant No. 2023Y0045); the Department of Finance, Fujian Province (Grant No. 006009210417); and the Fujian Medical University Student Innovation Training Program (Grant No. C2024177); Joint Funds for the Innovation of Science and Technology, Fujian Province (Grant No. 2024Y9009).

摘要/Abstract

摘要：

本研究旨在探讨房颤合并稳定性冠状动脉疾病(SCAD)对抗凝单药治疗的潜在影响。研究回顾性分析福建省立医院2021年11月至2023年6月服用利伐沙班进行单一抗凝治疗的住院非瓣膜性房颤患者(NVAF)。使用倾向性评分匹配(PSM)调整基线, 研究未合并SCAD患者(non-SCAD)与SCAD患者的稳态谷血药浓度、凝血指标、一年内发生的疗效终点事件(卒中、全身性栓塞、心肌梗死)以及安全终点事件(合并大出血和临床相关非大出血的复合结局(CRB), 轻微出血事件以及总出血事件)。使用限制性三次样条模型(RCS)和Cox比例风险模型进一步评估凝血酶原时间-国际标准化比值(PT-INR)与总出血事件发生风险之间的联系。研究回顾性收集了260例患者的ABCB1基因型, 合并用药以及其他基线情况, 通过PSM分析, 最终纳入了159例患者。结果显示, non-SCAD患者与SCAD患者的疗效终点事件及CRB无显著差异, 但SCAD患者具有更高的轻微出血事件(adjusted HR: 2.08, 95% CI: 1.07−4.04; P = 0.030)以及总出血事件发生风险(adjusted HR: 1.96, 95% CI: 1.05−3.64; P = 0.034)。存在心肌梗死史的SCAD患者相较于non-SCAD患者发生CRB (adjusted HR: 5.50, 95% CI: 1.00−30.14; P = 0.0497)及总出血事件(adjusted HR: 2.61, 95% CI: 1.09−6.27; P = 0.032)的风险更高。此外, SCAD患者还具有更大比例的较高PT-INR水平, 与总出血事件的发生风险呈非线性正相关。

关键词: 冠状动脉疾病, 房颤, 抗凝剂, 出血

Abstract:

This study aimed to investigate the influence of stable coronary artery disease (SCAD) on anticoagulation monotherapy. A total of 260 patients with nonvalvular atrial fibrillation who were admitted to Fujian Provincial Hospital between November 2021 and June 2023 were enrolled. The study compared the trough plasma concentrations of rivaroxaban, coagulation parameters, efficacy endpoints (stroke, systemic embolism, and myocardial infarction [MI]), and safety outcomes (including major bleeding, clinically relevant nonmajor bleeding [CRB], minor bleeding, and overall bleeding) between SCAD and non-SCAD patients after propensity score matching (PSM). Additionally, the association between prothrombin time-international normalized ratio (PT-INR) and total bleeding risk was analyzed using restricted cubic spline models and Cox proportional hazards regression. Baseline characteristics, including ABCB1 genotypes, concomitant medications, and other clinical variables, were retrospectively collected. Following PSM, 159 patients were included in the final analysis. The results indicated no significant differences in efficacy outcomes or CRB between SCAD and non-SCAD patients. However, SCAD patients exhibited a significantly higher risk of minor bleeding (adjusted HR: 2.08, 95% CI: 1.07–4.04; P = 0.030) and total bleeding (HR: 1.96, 95% CI: 1.05–3.64; P = 0.034). Moreover, among SCAD patients with a history of MI, the risk of CRB (HR: 5.50, 95% CI: 1.00–30.14; P = 0.0497) and total bleeding (HR: 2.61, 95% CI: 1.09–6.27; P = 0.032) was notably increased. Furthermore, in SCAD patients, PT-INR demonstrated a nonlinear positive correlation with total bleeding risk.

Key words: Coronary artery disease, Atrial fibrillation, Anticoagulants, Hemorrhage

Supporting: /attached/file/20251130/20251130160049_815.pdf

陈铭瑜, 黄有琪, 邓金珠, 林宇齐, 高红瑾, 陈敏. 合并稳定性冠状动脉疾病对非瓣膜性房颤患者单一抗凝治疗的潜在影响: 一项倾向性评分匹配研究[J]. 中国药学(英文版), 2025, 34(11): 989-1002.

Mingyu Chen, Youqi Huang, Jinzhu Deng, Yuqi Lin, Hongjin Gao, Min Chen. Impact of stable coronary artery disease on anticoagulation monotherapy in patients with nonvalvular atrial fibrillation: a propensity score-matched analysis[J]. Journal of Chinese Pharmaceutical Sciences, 2025, 34(11): 989-1002.

图/表 7

Figure 1. Study flowchart of patient selection.

Table 1. Baseline characteristics stratified by stable CAD before and after PSM.

Table 2. Efficacy and safety endpoint events in patients with NVAF after PSM.

Figure 2. Kaplan-Meier event curves for minor bleeding (a) and total bleeding (b) at the 1-year follow-up. Note: SCAD stable coronary artery disease.

Figure 3. Results of subgroup analysis for CRB (a) and total bleeding (b) after PSM. Note: SCAD: stable coronary artery disease; MI: myocardial infarction; CRB: composite of major bleeding and clinically relevant non-major bleeding; HR: hazard ratio; CI: confidence interval; TIA: transient ischemic attack; PT: prothrombin time; PT-INR: PT-international normalized ratio.

Figure 4. RCS for the association between PT-INR and the risk of rivaroxaban-related total bleeding in patients with or without SCAD. Note: RCS: restricted cubic spline; SCAD: stable coronary artery disease; PT: prothrombin time; PT-INR: PT-international normalized ratio.

Table 3. Associations between PT-INR and total bleeding events in patients with NVAF and SCAD.

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合并稳定性冠状动脉疾病对非瓣膜性房颤患者单一抗凝治疗的潜在影响: 一项倾向性评分匹配研究

Impact of stable coronary artery disease on anticoagulation monotherapy in patients with nonvalvular atrial fibrillation: a propensity score-matched analysis

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