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系統識別號 U0026-1808201411241500
論文名稱(中文) 抗血栓劑於合併心房顫動與急性冠心症的病患之療效與安全性評估
論文名稱(英文) Effectiveness and Safety of Antithrombotic Regimens in Patients with Atrial Fibrillation and Acute Coronary Syndrome
校院名稱 成功大學
系所名稱(中) 臨床藥學與藥物科技研究所
系所名稱(英) Institute of Clinical Pharmacy and Pharmaceutical sciences
學年度 102
學期 2
出版年 103
研究生(中文) 賴怡珊
研究生(英文) Yi-Shan Lai
學號 S66011023
學位類別 碩士
語文別 中文
論文頁數 99頁
口試委員 指導教授-高雅慧
指導教授-鄭靜蘭
口試委員-林文亮
口試委員-劉秉彥
口試委員-林立人
中文關鍵字 心房顫動  急性冠心症  抗血栓劑  療效  安全性 
英文關鍵字 atrial fibrillation  acute coronary syndrome  antithrombosis  warfarin  effectiveness  safety 
學科別分類
中文摘要 研究背景
心房顫動與急性冠心症皆需要使用抗血栓劑來預防栓塞,但約有5.3-7.6%急性冠心症患者亦合併有心房顫動,此類病患不只有較高的栓塞風險,亦有較高的死亡率,然而目前仍未有針對此類病患提出適當且一致性的抗血栓劑治療建議。

研究目的
本研究的目的是針對合併心房顫動及急性冠心症患者,進行抗血栓劑治療組合的療效與安全性評估。

研究方法
利用全民健保資料庫進行回溯性世代研究,收入2001-2008年首次診斷急性冠心症(ICD-9診斷碼410和411)且過去一年內有心房顫動患者(ICD-9診斷碼427.31),其抗血栓劑藥品的暴露共分成三種治療組合:「單用warfarin」、「雙重抗血小板」及「warfarin +抗血小板」,評估各治療組合的療效(含死亡、缺血性中風與心肌梗塞)與安全性(含腸胃道出血及顱內出血),我們會追蹤病患至發生研究事件或滿一年為止,並利用各研究事件發生後的嚴重度計算每個事件的相對比重,來衡量各治療組合與「單用warfarin」相比其淨臨床效益。

研究結果
共收入了3,210位合併心房顫動與急性冠心症的患者,總平均年齡72歲,且有高達96%的人CHA2DS2-VASc分數大於等於兩分,近七成的人HAS-BLED分數大於等於三分。在總療效方面(死亡、缺血性中風或心肌梗塞),與「單用warfarin」相比,「雙重抗血小板」會增加不良事件的風險,HR (95%CI)為1.54 (1.12-2.14),而「warfarin +抗血小板」則未達統計差異,HR (95%CI)為1.22 (0.83-1.78)。在總出血事件方面(顱內出血或腸胃道出血),「雙重抗血小板」未與「單用warfarin」組有統計差異,HR (95%CI)為0.84 (0.52-1.37),而「warfarin +抗血小板」則有較高的出血風險,HR (95%CI)為1.60 (1.00-2.57)。計算各組的淨臨床效益後,「單用warfarin」相較於其他治療組合具有較佳的淨臨床效益。

結論
對於合併心房顫動與急性冠心症患者,「單用warfarin」即具有其淨臨床效益,在warfarin的基礎上再加上抗血小板劑其療效與「單用warfarin」相當,但會增加出血的風險。
英文摘要 Acute coronary syndrome (ACS) patients concomitant with atrial fibrillation (AF) had higher risk for thrombosis and mortality than those without. However, the evidence of appropriate antithrombotic regimens was limited and incosisitance. We conducted a retrospective cohort study by using Taiwan National Health Insurance Database to evaluate the effectiveness and safety of three antithrombotic regimens in patients with ACS and AF. The results showed that the combination of anticoagulant and antiplatelet had equivalent effectiveness to single warfarin but may increase the bleeding risk. Compared to single warfarin, dual antiplatelet was safer for intracerebral hemorrhage but enhancing the thrombosis events. The net clinical benefit presented single warfarin was the best choice, especially for patients with high thrombosis risk. However, for those patients with higher intracerebral hemorrhage risk or contraindication for warfarin, dual antiplatelet may be another choice.
論文目次 中文摘要I
英文延伸摘要III
誌謝VII
目錄VIII
表目錄XI
圖目錄XII
縮寫與名詞對照表XIII
第1部分、抗血栓劑各種治療組合於合併心房顫動與急性冠心症之病患的療效與安全性評估1
第1章 研究背景1
第2章 文獻回顧2
第1節 心房顫動疾病簡介2
2.1.1 流行病學2
2.1.2 心房顫動導致栓塞之致病機轉2
2.1.3 心房顫動者發生中風的危險因子3
2.1.4 現今治療指引建議4
2.1.5 各種抗血栓劑治療組合的比較7
2.1.6 亞洲族群使用warfarin的特殊性9
第2節 急性冠心症疾病簡介11
2.2.1 流行病學11
2.2.2 急性冠心症致病機轉12
2.2.3 急性冠心症者的預後及風險評估12
2.2.4 抗血栓劑的選擇14
2.2.5 各種抗血栓劑治療組合的比較14
第3節 合併心房顫動及急性冠心症疾病簡介17
2.3.1 流行病學17
2.3.2 現今治療建議 17
2.3.3 抗血栓劑治療組合療效比較17
2.3.4 抗血栓劑治療組合出血風險比較19
2.3.5 統合分析20
第3章 研究目的29
第4章 研究方法30
第1節 研究設計30
4.1.1 研究類型30
4.1.2 研究材料與工具30
4.1.3 研究族群31
4.1.4 抗血栓劑治療組合定義31
4.1.5 研究事件32
4.1.6 變數因子(栓塞、出血風險、過去用藥及手術史)33
第2節 研究變相及操作定義說明35
第3節 統計分析41
4.3.1 描述性統計41
4.3.2 推論性統計41
4.3.3 敏感性分析41
4.3.4 淨臨床效益評估42
第5章 研究結果44
第1節 研究族群基本特性分布44
第2節 主要研究事件46
第3節 次要研究事件46
第4節 敏感性分析47
第5節 淨臨床效益47
第6節 風險因子分析48
第6章 研究討論67
第1節 研究族群基本特性與抗血栓劑使用情形67
第2節 抗凝血、抗血小板或合併使用68
第3節 抗血栓劑治療組合與缺血性中風的相關性69
6.3.1 與國外文獻比較69
6.3.2 亞洲族群使用warfarin的特殊性69
第4節 抗血栓劑治療組合與心肌梗塞的相關性70
第5節 抗血栓劑治療組合與出血事件的相關性71
第6節 療效與安全性評估71
第7節 研究限制72
第7章 結論與建議74
第8章 未來研究方向75
第2部分、藥事服務:成大醫院住院藥局退藥原因分析76
第1章 服務背景76
第2章 研究方法77
第3章 研究結果79
第4章 改善退藥數量方法討論85
第5章 結論與建議90
參考文獻91
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