苯二氮平類藥物暴露量與深層靜脈血栓形成風險之劑量反應關係探討

苯二氮平類藥物(Benzodiazepines, BZDs)因具有鎮靜安眠與抗焦慮等藥理特性，長期以來廣泛應用於臨床，為安眠藥使用種類之大宗。然而，近年來有愈來愈多研究指出，鎮靜安眠藥的使用可能降低個體的活動力，進而提高靜脈血栓栓塞症(Venous Thromboembolism, VTE)之風險。本研究旨在進一步探討BZDs與深層靜脈血栓 (Deep Vein Thrombosis, DVT)形成之間的潛在劑量-反應關係。本研究採用病例對照研究設計，利用臺灣全民健康保險研究資料庫，自2002年至2018年間篩選首次診斷為DVT的個案作為病例組，並依年齡、性別及投保地區進行 1:4 配對，選取未診斷DVT的對照個案。為控制潛在干擾因素，進一步納入共病症與其他用藥史進行多變量邏輯斯迴歸分析。同時進行分層分析，以探討不同年齡、性別與用藥時間的群體中，BZDs與 DVT 之間的關聯性是否一致。分析結果顯示，曾使用 BZDs的個案其罹患DVT的風險顯著高於未使用者，調整後勝算比(adjusted Odds Ratio, aOR)為 1.66 (95%信賴區間: 1.54–1.79，p < .001)。進一步探討劑量效應時發現，BZDs的每日定義劑量(Defined Daily Dose, DDD)與 DVT風險呈正相關。與未使用BZDs者相比，每日平均使用劑量為 <0.5 DDD、0.5–0.9 DDD 和 ?1 DDD/per-day 的個案，其發生DVT的風險分別為 1.65 倍、2.09 倍與 2.16 倍，存在具統計顯著性的正相關劑量依賴關係(p for trend = 0.001)。臨床醫師在開立BZDs處方時，應審慎考量患者的個別風險因子，並評估長期使用對靜脈血栓形成風險的潛在影響，以降低不必要的醫療風險與併發症。

This population-based case-control study investigated the dose-response relationship between benzodiazepines (BZDs) and the risk of deep vein thrombosis (DVT) using data from Taiwan’s National Health Insurance Research Database, which contains records of two million patients. The study included individuals aged 20 years and older who were newly diagnosed with DVT between 2002 and 2018. A 1:4 matching by age, sex, and county was applied to select non-DVT subjects from 2000 to 2018, resulting in 12,546 DVT cases and 50,184 matched controls. Multivariable logistic regression analysis was used to assess the association between BZDs use and the risk of DVT, adjusting for potential confounding factors. In addition, stratified analyses were conducted based on age, sex, and follow-up duration to examine possible variations in the dose-response effect. The findings showed that BZDs prescription was associated with a higher risk of DVT, with an adjusted odds ratio (aOR) of 1.66 (95% CI, 1.54–1.79; p < .001). The risk of DVT increased with higher defined daily doses (DDD) /pre-day of BZDs. Compared with non-users, patients with an average daily dose of <0.5, 0.5–0.9, and ?1 DDD/per-day had 1.65-, 2.09-, and 2.16-fold higher risks, respectively. The results indicate a clear dose-response relationship between BZDs use and the occurrence of DVT in this Asian population. These findings highlight the importance of evaluating the risks and benefits when prescribing BZDs, especially for individuals with existing risk factors for thrombotic events.