Pharmacodynamic Drug-Drug Interactions and Bleeding Outcomes in Patients with Atrial Fibrillation Using Non-Vitamin K Antagonist Oral Anticoagulants: a Nationwide Cohort Study.

IF 3.1 3区医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS

Cardiovascular Drugs and Therapy Pub Date : 2025-02-01 Epub Date: 2023-11-06 DOI:10.1007/s10557-023-07521-5

Maxim Grymonprez, Andreas Capiau, Stephane Steurbaut, Koen Boussery, Els Mehuys, Annemie Somers, Mirko Petrovic, Tine L De Backer, Lies Lahousse

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引用次数: 0

Abstract

Purpose: Pharmacodynamic drug-drug interactions (PD DDIs) may influence the safety of non-vitamin K antagonist oral anticoagulants (NOACs), but the extent to which PD DDIs increase bleeding risks, remains unclear. Therefore, the impact of PD DDIs on bleeding outcomes in NOAC-treated patients with atrial fibrillation (AF) was investigated.

Methods: Using Belgian nationwide data, NOAC-treated AF patients were included between 2013-2019. Concomitant use of PD interacting drugs when initiating NOAC treatment was identified.

Results: Among 193,072 patients, PD DDIs were identified in 114,122 (59.1%) subjects. After multivariable adjustment, concomitant use of PD interacting drugs was associated with significantly higher risks of major or clinically-relevant non-major bleeding (adjusted hazard ratio (aHR) 1.19, 95% confidence interval (CI) (1.13-1.24)), gastrointestinal (aHR 1.12, 95%CI (1.03-1.22)), urogenital (aHR 1.21, 95%CI (1.09-1.35)) and other bleeding (aHR 1.28, 95%CI (1.20-1.36)), compared to NOAC-treated AF patients without PD interacting drug use. Increased bleeding risks were most pronounced with P2Y₁₂ inhibitors (aHR 1.62, 95%CI (1.48-1.77)) and corticosteroids (aHR 1.53, 95%CI (1.42-1.66)), followed by selective serotonin or serotonin and norepinephrine reuptake inhibitors (SSRI/SNRI, aHR 1.26, 95%CI (1.17-1.35)), low-dose aspirin (aHR 1.14, 95%CI (1.08-1.20)) and non-steroidal anti-inflammatory drugs (NSAID, aHR 1.10, 95%CI (1.01-1.21)). Significantly higher intracranial bleeding risks in NOAC users were observed with SSRI/SNRIs (aHR 1.50, 95%CI (1.25-1.81)) and corticosteroids (aHR 1.49, 95%CI (1.21-1.84)).

Conclusion: Concomitant use of PD interacting drugs, especially P2Y₁₂ inhibitors and corticosteroids, was associated with higher major, gastrointestinal, urogenital, and other bleeding risks in NOAC-treated AF patients. Remarkably, higher intracranial bleeding risks were observed with SSRI/SNRIs and corticosteroids.

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使用非维生素K拮抗剂口服抗凝剂治疗心房颤动患者的药效学药物相互作用和出血结果：一项全国性队列研究。

目的：药效学药物相互作用（PD-DDI）可能影响非维生素K拮抗剂口服抗凝剂（NOAC）的安全性，但PD-DDI增加出血风险的程度尚不清楚。因此，研究了PD-DDI对NOAC治疗的心房颤动（AF）患者出血结果的影响。方法：使用比利时全国数据，纳入2013-2019年间接受NOAC治疗的AF患者。发现在开始NOAC治疗时同时使用PD相互作用药物。结果：在193072名患者中，114122名（59.1%）受试者中发现了PD DDI。多变量调整后，同时使用PD相互作用药物与重大或临床相关的非重大出血（调整后的危险比（aHR）1.19，95%置信区间（CI）（1.13-1.24））、胃肠道（aHR 1.12，95%CI（1.03-1.22），与没有PD相互作用药物使用的NOAC治疗的AF患者相比。P2Y12抑制剂（aHR 1.62，95%CI（1.48-1.77））和皮质类固醇（aHR 1.53，95%CI（1.42-1.66））的出血风险增加最为明显，其次是选择性5-羟色胺或5-羟色胺和去甲肾上腺素再摄取抑制剂（SSRI/SNRI，aHR 1.26，95%CI（1.17-1.35）），低剂量阿司匹林（aHR 1.14，95%CI（1.08-1.20，尤其是P2Y12抑制剂和皮质类固醇，与NOAC治疗的AF患者更高的主要、胃肠道、泌尿生殖道和其他出血风险相关。值得注意的是，使用SSRI/SNRI和皮质类固醇的颅内出血风险更高。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cardiovascular Drugs and Therapy 医学-心血管系统

CiteScore

8.30

自引率

0.00%

发文量

110

审稿时长

4.5 months

期刊介绍： Designed to objectively cover the process of bench to bedside development of cardiovascular drug, device and cell therapy, and to bring you the information you need most in a timely and useful format, Cardiovascular Drugs and Therapy takes a fresh and energetic look at advances in this dynamic field. Homing in on the most exciting work being done on new therapeutic agents, Cardiovascular Drugs and Therapy focusses on developments in atherosclerosis, hyperlipidemia, diabetes, ischemic syndromes and arrhythmias. The Journal is an authoritative source of current and relevant information that is indispensable for basic and clinical investigators aiming for novel, breakthrough research as well as for cardiologists seeking to best serve their patients. Providing you with a single, concise reference tool acknowledged to be among the finest in the world, Cardiovascular Drugs and Therapy is listed in Web of Science and PubMed/Medline among other abstracting and indexing services. The regular articles and frequent special topical issues equip you with an up-to-date source defined by the need for accurate information on an ever-evolving field. Cardiovascular Drugs and Therapy is a careful and accurate guide through the maze of new products and therapies which furnishes you with the details on cardiovascular pharmacology that you will refer to time and time again.