非維他命K拮抗劑藥物對心房顫動合併腎功能正常者與慢性腎臟病第1-3期成人患者預後的影響：一項多中心傾向評分配對分析

中文摘要研究背景慢性腎臟病（Chronic Kidney Disease, CKD）是一種進行性疾病，其定義為腎絲球過濾率（glomerular filtration rate, GFR）低於60 mL/min/1.73 m²、存在腎臟損傷指標（如蛋白尿或血尿），或兩者兼具，且持續至少三個月。本研究利用TriNetX美國協作網絡（TriNetX US Collaborative Network）資料庫，納入腎功能正常者及慢性腎臟病第1至3期成年患者。心房顫動患者需接受抗凝血治療以預防腦中風。Warfarin為維生素K拮抗劑，可間接抑制凝血因子II、VII、IX及X，主要經肝臟代謝；相較之下，非維生素K拮抗口服抗凝血劑（Non-vitamin K antagonist oral anticoagulants, NOACs）可直接抑制凝血因子IIa或Xa，具有作用機轉較具選擇性及起效快速的優點，但其代謝同時涉及腎臟與肝臟。本研究利用真實世界資料，比較腎功能正常者以及CKD第1至3期患者使用NOACs與Warfarin之臨床預後差異，主要目的為評估何種抗凝治療可提供較佳的預後效益。研究設計本研究利用TriNetX資料庫辨識腎功能正常者與慢性腎臟病(Chronic Kidney Disease, CKD)第1期至第3期的成年患者。我們使用了TriNetX 美國網絡(US Network)於2015年6月1日至 2023年6月30日期間的資料。納入條件為年齡18歲以上，且於急診就診或住院期間首次被診斷為心房顫動(Atrial Fibrillation, AF)之患者，診斷依據為國際疾病分類第十版(ICD-10)代碼。研究對象依所使用的抗凝血藥物分為兩組：非維生素 K 拮抗劑口服抗凝血藥物(Non-Vitamin K Antagonist Oral Anticoagulants, NOACs)使用組，以及華法林(Warfarin)使用組。本研究的主要結果為10年內發生的改良型主要心血管不良事件(modified Major Adverse Cardiovascular Events, modified MACE)之風險，其組成包括全因死亡(All-cause mortality)、心肌梗塞(Myocardial infarction, MI)及缺血性腦中風(Ischemic stroke)。次要結果則評估重大出血事件，包括顱內出血(Intracranial hemorrhage)及腸胃道出血(GI bleeding)。研究結果研究結果顯示，與Warfarin使用者相比， NOACs使用者在主要研究結果：修正主要心血管不良事件(modified Major Adverse Cardiovascular Events, modified MACEs)方面具有較低的風險(HR=0.903，95% CI：0.875–0.932，P＜0.0001)。修正主要心血管不良事件的三個子集團中：全因死亡率和缺血性腦中風也都於NOACs使用者比起Warfarin使用者有較低的風險。心肌梗塞部分則是NOACs使用者比起Warfarin使用者風險差異不大。在次要研究終點方面NOACs使用者發生重大出血事件(Major bleeding)的風險亦顯著低於Warfarin使用者(HR=0.722，95% CI：0.695–0.750，P＜0.0001)。重大出血事件的兩個子集團：顱內出血和腸胃道出血也都於NOACs使用者比起Warfarin使用者有較低的風險。此外，在陰性對照結果(Negative control outcomes)分析中NOACs使用者與Warfarin使用者於流行性感冒和肺炎組、泌尿道感染、退化性關節炎組別中皆呈無相關性。結論與建議在腎功能正常者與慢性腎臟病第1至第3期患者合併心房顫動患者中，相較於使Warfarin的患者，使用NOACs的患者在大多數修正主要心血管不良事件(modified MACEs)及各類重大出血事件方面均呈現較低風險，顯示NOACs在療效與安全性上可能優於Warfarin，具有較佳的臨床治療效益，亦可減少重大出血、顱內出血以及腸胃道出血等不良事件的發生。

英文摘要BackgroundChronic kidney disease (CKD) is a progressive disorder defined by a glomerular filtration rate (GFR) <60 mL/min/1.73 m², markers of kidney damage, or both, persisting for at least three months. Using the TriNetX US Collaborative Network, we identified adults with normal renal function people and CKD stages 1–3 patients. Patients with atrial fibrillation require anticoagulation to prevent stroke. Warfarin, a vitamin K antagonist, indirectly inhibits coagulation factors II, VII, IX, and X and is mainly metabolized by the liver. In contrast, non-vitamin K antagonist oral anticoagulants (NOACs) directly inhibit factor IIa or Xa, providing more targeted anticoagulation with rapid onset, although they undergo both renal and hepatic metabolism. This study compared NOACs and warfarin in patients with CKD stages 1–3 to evaluate differences in clinical outcomes using real-world data. The primary objective was to determine which therapy offers better prognostic benefit, while the secondary outcome assessed major bleeding, including intracranial and gastrointestinal hemorrhage.DesignWe utilized the TriNetX database to identify adult as normal renal function people and the patients with chronic kidney disease (CKD) stages 1-3. Data from the TriNetX US Network was queried for the period between June 1, 2015, and June 30, 2023. We included patients aged 18 years or older who had an initial atrial fibrillation (AF) diagnosis recorded during an emergency visit or hospitalization, based on ICD-10 codes. Patients were divided into two groups: NOACs users and warfarin users. The primary outcomes of this study were the 10-year risk of modified major adverse cardiovascular events (MACE), encompassing all-cause mortality, myocardial infarction (MI), and ischemic stroke.Results NOACs users were associated with a lower risk for modified major adverse cardiac events (MACEs) as the primary outcome compared to warfarin users (HR:0.903, CI:0.875-0.932, P value<0.0001). NOACs users were also associated with a lower risk for major bleeding as the secondary outcome compared to warfarin users (HR:0.722, CI:0.695-0.750, P value<0.0001). Subgroup analysis revealed among all-cause mortality (HR:0.864, CI:0.829-0.900, P value<0.0001), ischemic stroke (HR:0.902, CI:0.848-0.959, P value=0.0009), intracranial hemorrhage (HR:0.623, CI:0.553-0.702, P value<0.0001), GI bleeding (HR:0.888, CI:0.833-0.946, P value=0.0003) had lower risk compared to warfarin users. In the negative control outcome, CKD stage 4 or end stage renal disease(ESRD) (HR:0.879, CI:0.837-0.922, P value<0.0001) and acute kidney injury (HR:0.897, CI:0.863-0.932, P value<0.0001) showed a lower risk among NOACs users compared to warfarin users.Conclusion and Recommendations NOACs users, compared to warfarin users, had a lower risk in most modified MACEs and all major bleeding events in normal renal function people and the patients of chronic kidney disease(CKD) stage 1-3 with atrial fibrillation(AF).