研究背景
急性冠狀動脈症候群（Acute coronary syndrome, ACS）合併心房顫動（Artrial fibrillation, AF）及慢性腎臟病（Chronic kidney disease, CKD）之患者同時面臨高栓塞與高出血風險，抗血栓策略之選擇極具挑戰性。現行指引建議急性期後採用雙重治療（Dual therapy, DT：口服抗凝血劑合併單一抗血小板藥物）作為此類患者之優先抗血栓策略，然而真實世界觀察性研究顯示，雙重抗血小板治療（Dual antiplatelet therapy,DAPT）仍是臨床實務中最常見的處方型態，指引依從性明顯不足。現有大型隨機對照試驗系統性排除重度 CKD 患者，且均以三重療法（Triple therapy, TT）為對照，缺乏 DT 對比DAPT 之直接真實世界證據。本研究旨在利用兩個獨立資料庫，評估 DT相較於 DAPT 在 ACS 合併 AF 及 CKD 族群中之療效與安全性。
研究方法
本研究採回溯性世代研究設計，同時利用台灣全民健保資料庫（National Health Insurance Database , NHID）與 TriNetX 美國協作網絡兩個獨立資料庫。納入發生 ACS 並接受經皮冠狀動脈介入術（Percutaneous coronary intervention, PCI） ，同時具有 AF及 CKD 病史診斷之患者，NHID 以傾向分數調整法（Propensity score adjustment）進行組間平衡； TriNetX 以 1:1 傾向分數配對。主要療效終點為主要心血管不良事件（心肌梗塞、中風及全因性死亡之複合事件），主要安全性終點為重大出血事件。此外，本研究計算淨臨床效益以綜合評估兩種策略之整體效益權衡，並執行多項敏感性分析及 eGFR 分層次族群分析。
研究結果
NHID 分析最終納入 DAPT 組 610 名及 DT 組 153 名；TriNetX 分析經 1:1 傾向分數配對後各納入 379 名。 NHID 分析中， DT 組之 MACE 發生率低於 DAPT 組（24.8vs 28.3 per 100 person-years），傾向分數調整後方向支持 DT 之療效優勢（HR 0.872，95% CI 0.679–1.119），惟因 DT 組樣本數有限未達統計顯著；出血方面，兩組間沒有統計上的顯著差異（HR 1.209，95% CI 0.883–1.655） 。TriNetX 分析結果，配對後 DT組之 MACE 風險顯著低於 DAPT 組（HR 0.659，95% CI 0.558–0.777），AMI（HR 0.578 ，）及全因性死亡（HR 0.760） 亦同； 安全性終點方面，兩個資料庫之重大出血、GI 出血及 ICH 均未達統計顯著。NCB 分析方面，NHID 及 TriNetX 主要分析皆呈正向淨效益，然 NHID PSM 敏感性分析控制 ESRD 比例後，以複合出血終點計算之NCB 轉為負值， 若以顱內出血單獨計算則維持正值， 提示 NCB 結果取決於出血終點定義及族群特性。
結論
在 ACS 合併 AF 且合併 CKD 患者中，本研究於兩個獨立真實世界資料庫中均觀察到 DT 相較於 DAPT 具有較佳缺血事件保護之一致方向，且於現有樣本數下未觀察到重大出血風險顯著增加 ，整體淨臨床效益趨勢優於 DAPT。NCB 分析結果因分析方法不同而有所差異 ，主要分析支持 DT 具有正向淨效益， PSM 敏感性分析則提示腸胃道出血差距可能影響整體效益平衡，臨床決策應個別化評估患者之缺血與出血風險，並重視可調整之腸胃道出血危險因子。 本研究補充大型隨機對照試驗於 CKD 族群（包含 ESRD 患者）證據不足之缺口，可作為 ACS 合併 AF 且合併 CKD 患者抗血栓治療策略之臨床參考。

Patients with ACS, AF, and CKD represent a particularly challenging population because they are simultaneously at high risk for thromboembolic and bleeding events. Although current guidelines recommend DT following the acute phase of ACS, DAPT remains frequently prescribed in routine clinical practice. Moreover, patients with advanced CKD have been excluded from major randomized controlled trials, resulting in limited evidence to guide antithrombotic treatment decisions in this high-risk population.
To address this evidence gap, this retrospective cohort study utilized two independent real-world databases with distinct geographic and healthcare settings:the NHID and the TriNetX US Collaborative Network. Eligible patients were diagnosed with ACS had undergone PCI,with history of AF, and CKD and. Patients receiving DT were compared with those receiving DAPT. The primary efficacy outcome was MACE, defined as a composite of myocardial infarction, stroke, and all-cause mortality. The primary safety outcome was major bleeding.
The NHID cohort included 610 patients receiving DAPT and 153 patients receiving DT. Although the DT group demonstrated a lower incidence rate of MACE than the DAPT group , the adjusted hazard ratio favored DT without reaching statistical significance (HR 0.872, 95% CI 0.679–1.119), likely reflecting the relatively small sample size and limited statistical power of the DT group. And no statistically significant differences in major bleeding outcomes were observed between the two treatment groups. In contrast, the TriNetX cohort, which included 379 matched pairs after propensity score matching, showed that DT was associated with significantly lower risks of MACE (HR 0.659, 95% CI 0.558–0.777), acute myocardial infarction , and all-cause mortality compared with DAPT. Major bleeding, gastrointestinal bleeding, and intracranial hemorrhage were not significantly different between treatment groups. Despite differences in patient characteristics, healthcare systems, and analytical approaches, both databases consistently demonstrated a favorable direction of effect for DT with respect to ischemic outcomes without evidence of a significant increase in major bleeding.
Net clinical benefit analyses generally supported DT over DAPT, although sensitivity analyses suggested that gastrointestinal bleeding may influence the overall benefit–risk balance under certain analytical approaches. These findings highlight the importance of individualized antithrombotic therapy based on both ischemic and bleeding risks.
Overall, this study provides real-world evidence supporting DT as a favorable antithrombotic strategy for patients with ACS, AF, and CKD, including those with ESRD, and helps address the evidence gap left by randomized clinical trials.

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