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系統識別號 U0026-2108201412581000
論文名稱(中文) 非瓣膜性心房顫動病患使用新型口服抗凝血劑之安全性評估 – 單一醫學中心使用經驗
論文名稱(英文) Assessment on Safety of New Oral Anticoagulants for Nonvalvular Atrial Fibrillation – A Single Medical Center Experience
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) 賴穎萱
研究生(英文) Ying-Hsuan Lai
學號 s66011015
學位類別 碩士
語文別 中文
論文頁數 117頁
口試委員 指導教授-高雅慧
指導教授-鄭靜蘭
口試委員-黃千惠
口試委員-林立人
口試委員-李政翰
中文關鍵字 台灣  新型口服抗凝血劑  安全性  dabigatran  rivaroxaban 
英文關鍵字 dabigatran  rivaroxaban  safety  real-world  Taiwan 
學科別分類
中文摘要 研究背景
國內新核准的兩個新型口服抗凝血劑(new oral anticoagulants, NOACs) dabigatran及rivaroxaban,被建議用在罹患非瓣膜性心房顫動的病患,預防中風或全身性栓塞的發生,尤其是那些無法耐受warfarin的患者。目前台灣族群使用NOACs之安全性的相關研究仍不多。
研究目的
本研究目的為評估dabigatran、rivaroxaban及warfarin於台灣非瓣膜性心房顫動病人的安全性。包括重大出血(顱內出血、呼吸道出血、腸胃出血與泌尿道出血)、次要出血(其他非重大出血的出血事件),以及其他任何病歷記載的不良反應事件發生率。
研究方法
本研究為回溯性世代研究,納入有心房顫動診斷,且於2013年3月至2014年2月間開立dabigatran或rivaroxaban者,以及於2011年5月至2014年4月使用warfarin者,並且排除過去曾有瓣膜疾病或過去病史記錄不完全的病患。我們以病歷回顧的方式記錄出血、栓塞與其他不良反應事件,主要研究終點為出血發生率(包含重大出血及次要出血)與不良反應事件發生率。
研究結果
本研究共納入437位非瓣膜性心房顫動患者,其中rivaroxaban組(R組)為128人,dabigatran組(D組)為150人,warfarin組(W組)為159人。三組平均CHADS2 score分數分別為:R組2.54±1.18,D組2.30±1.18,W組2.39±1.35,沒有顯著差異。HAS-BLED score分別為:R組3.2±1.19,D組3.03±1.10,W組3.42±1.34,其中D組與W組達統計學上差異(p=0.011)。主要研究終點『總出血發生率』:R組(27.57 %/year) 與D組(28.25 %/year) 的發生率較W組(33.74 %/year)略低一些,但未達統計學上顯著差異(R vs. W:p=0.098,D vs. W:p=0.181)。另外,NOACs的其他不良反應事件比warfarin多。Dabigatran病患最常發生的副作用為腸胃不適(粗發生率:7.33%)。
結論
本研究提供台灣非瓣膜性心房顫動病患在臨床上使用dabigatran與rivaroxaban的出血事件發生率。台灣族群使用dabigatran與rivaroxaban的總出血發生率較warfarin低,但未達統計學上顯著差異。雖然本研究觀察到NOACs的安全性與warfarin沒有顯著差異,但由於觀察時間短、樣本數少,因此我們現在仍無法下結論,期待未來有更長觀察時間以及更多收案人數的研究。
英文摘要 Although new oral anticoagulants (NOACs), dabigatran and rivaroxaban, are recommended for prevention of thromboembolism in patients with atrial fibrillation especially those who cannot tolerate warfarin, safety information in Taiwan population is limited. Meanwhile, relative bleeding risk between NOACs remains unknown due to lack of head-to-head comparison. To investigate the bleeding risk of dabigatran and rivaroxaban and to compare safety between NOACs and warfarin, we conducted a retrospective cohort study in patients who had nonvalvular atrial fibrillation. In total, we included 437 patients. The crude rate of total bleeding was 27.57 per 100 person-years in rivaroxaban group, 28.25 per 100 person-years in dabigatran group and 37.74 per 100 person-years in warfarin group. No significant differences were found between two study drugs and warfarin, although the incidences of total bleeding of NOACs were lower than warfarin. However, there seemed to be more adverse events in NOACs than in warfarin. Because of small sample size and short follow-up duration, we cannot conclude the safety differences between NOACs and warfarin. Further studies in Taiwan population are warranted.
論文目次 中文摘要...........I
Extended Abstract.........III
誌謝............VI
目錄...........VIII
表目錄............XI
圖目錄...........XIII
縮寫與全名對照表........XIV
第 1 部分、 非瓣膜性心房顫動病患使用新型口服抗凝血劑之安全性評估 – 單 一醫學中心使用經驗 ............1
第 1 章、 研究背景...........1
第 2 章、 文獻回顧...........2
第 1 節、 心房顫動之流行病學 ..........2
第 2 節、 心房顫動與栓塞 ..........3
第 3 節、 Warfarin 的療效與安全性 .........6
第 4 節、 新型口服抗凝血劑介紹 ........7
第 5 節、 現今治療指引建議 ..........13
第 6 節、 與 NOAC 之療效和安全性相關的文獻.....15
第 3 章、 研究目的...........33
第 4 章、 研究方法...........34
第 1 節、 研究設計 ............34
第 2 節、 研究名詞、研究變項與操作定義 ......38
第 3 節、 研究流程 ............40
第 4 節、 統計分析 ............43
第 5 章、 研究結果...........45
第 1 節、 研究對象納入與排除 ........45
第 2 節、 研究對象基本資料分析 ........49
第 3 節、 主要研究事件 (Primary outcome) ......58
第 4 節、 次要研究事件 (Secondary outcome) ......64
第 5 節、 次群組分析 (Subgroup analysis) ......70
第 6 章、 討論.............74
第 1 節、 研究對象基本資料結果分析 ........74
第 2 節、 NOACs 於台灣族群的安全性與療效 ......76
第 3 節、 NOACs 於中度腎功能不全病人的出血風險 ....87
第 4 節、 過去使用 warfarin 經驗與出血風險.......88
第 5 節、 研究優勢與限制 ..........90
第 7 章、 結論與建議 ............93
第 8 章、 未來研究方向 ..........94
第 2 部分、 臨床藥事服務:門診病患使用新型口服抗凝血劑之順從性調查 96
第 1 章、 服務緣起...........96
第 2 章、 服務目的與方法 ..........98
第 1 節、 目的.............98
第 2 節、 方法.............98
第 3 章、 結果.............101
第 1 節、 服務對象基本資料 ..........101
第 2 節、 服藥順從性分析 ..........102
第 4 章、 衛教感想與建議 ..........104
參考文獻..........106
附件...........113
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