研究背景:
心房顫動疾病對全球人口的生活產生相當大的影響，隨著全球人口老齡化，這個問題對公共衛生和醫療系統的負擔日益增加。心房顫動病人常伴隨焦慮和抑鬱症狀，因此他們更容易出現自殺傾向和自殺風險，故評估心房顫動病人的自殺傾向和自殺風險非常重要。動物研究發現維生素K可以通過調節大腦中神經醯胺系統，可以促進神經細胞的新生，有助於預防焦慮與憂鬱症狀的發生。過去研究顯示相較於使用warfarin的心房顫動病人，使用非維生素K拮抗劑口服抗凝血藥物(NOACs)會顯著降低焦慮和憂鬱症狀風險。鑑於心理健康疾病與自殺風險之間的密切關聯，我們假設使用非維生素K拮抗劑口服抗凝血藥物(NOACs)或warfarin可能存在不同的自殺企圖和自殺風險。然而，口服抗凝血劑與自殺企圖和自殺之間的相關性尚未深入了解。我們模擬了一項目標試驗，以比較在心房顫動患者中新使用非維生素K拮抗劑口服抗凝血藥物(NOACs)和維生素K拮抗劑（warfarin）發生自殺企圖和自殺的風險差異。
研究目的:
本研究旨在比較新使用非维生素K拮抗劑口服抗凝血藥物(NOACs)和維生素K拮抗劑（warfarin）治療的心房顫動病人發生自殺傾向與自殺的風險差異。
研究方法:
本研究使用模擬臨床試驗架構(target trial emulation framework)進行全國性世代研究，資料來源為2009至2020年臺灣衛生福利部衛生福利資料科學中心加值資料，收錄2012至2020年年齡超過20歲且新使用口服抗凝血藥物治療的心房顫動病人，為了模擬目標試驗中的隨機分派，我們使用傾向分數進行細項分組加權以平衡兩組病人特徵。主要研究終點為自殺結果，包含自殺傾向和自殺。我們利用意向分析和符合計畫書分析評估因果關係，並應用特定因素風險模型(cause-specific hazards models)和次分佈瞬間風險模型(subdistribution hazards models)計算各研究結果風險比和95%信賴區間。
研究結果:
利用傾向分數進行細項分組加權後，加權人數分別為103,768位使用非維生素K拮抗劑口服抗凝血藥物和40,877位使用warfarin，非維生素K拮抗劑口服抗凝血藥物組別整體平均追蹤時間為2.75年，warfarin組別為4.31年，平均治療效應分析（ATE）中，使用非維生素K拮抗劑口服抗凝血藥物病人的自殺結果累積發生率為每1000人年4.16例，而使用warfarin病人的自殺結果累積發生率為每1000人年4.89例。與warfarin相比，使用非維生素K拮抗劑口服抗凝血藥物病人在自殺結果（風險比，0.85；95% CI，0.75至0.97）的風險顯著降低。在敏感性分析中，排除慢性腎臟疾病病史的病人後，其結果與主分析一致。在符合計畫書分析中，與warfarin相比，使用非維生素K拮抗劑口服抗凝血藥物病人在自殺結果的風險有較低的趨勢（風險比，0.79；95% CI，0.60至1.05）。在次分佈瞬間風險模型分析中，與warfarin相比，使用非維生素K拮抗劑口服抗凝血藥物病人在自殺結果的風險有較低的趨勢（風險比，0.89；95% CI，0.81至0.98）。
結論:
綜上所述，我們研究結果顯示，與warfarin相比，使用非維生素K拮抗劑口服抗凝血藥物病人在自殺結果的風險顯著降低。考慮到自殺對心房顫動患者的醫療照護所產生的嚴重負面影響，當醫師為病患選擇使用口服抗凝血藥物時，相較於warfarin，非維生素K拮抗劑口服抗凝血藥物可能是更好的治療選擇，以降低自殺傾向與自殺發生風險。

Background:
Vitamin K has been shown to reduce ceramides and pro-inflammatory processes in the hippocampus, which can have positive effects on alleviating anxious and depressive symptoms. Clinical studies have shown that warfarin is associated with a higher risk of anxious and depressive symptoms compared to non-vitamin K antagonist oral anticoagulants (NOACs). We have hypothesized that NOACs or warfarin may have different risks of suicidal attempts and suicide.
Method:
We aimed to evaluate non-vitamin K antagonist oral anticoagulants and warfarin for the risk of suicidal attempts and suicide among patients with atrial fibrillation. We emulated a target trial using Taiwan's National Health Insurance Database to include patients with AF aged over 20 years, newly receiving oral anticoagulants (i.e., NOACs and warfarin) during 2012-2020. We implemented the propensity score by fine stratification to improve exchangeability between the two treatment groups.
Results:
NOACs were associated with a lower hazard of suicidal outcomes (HR, 0.85; 95%CI, 0.75 to 0.97 for ATE) compared to warfarin. Several sensitivity analyses supported this finding. In on-treatment analysis, the effect estimates remained larger, with lower trends for the hazard of suicidal outcomes for NOACs (HR, 0.79; 95%CI, 0.60 to 1.05 for ATE) compared to warfarin.
Conclusion:
In conclusion, considering the negative impact of suicide on the healthcare of patients with AF, NOACs may be a preferable treatment option over warfarin in reducing the risk of suicidal outcomes for patients who require oral anticoagulant therapy.

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