中文摘要
研究背景及目的:
目前心房顫動的指引建議,所有心房顫動的病人應接受長期抗凝血劑治療且國際正常化比率( INR )應控制在2到3中間,除非年齡少於六十五歲且無任何中風之危險因子或對使用香豆素( warfarin)有禁忌。對於非瓣膜性心房顫動,使用抗凝血劑且INR至少2以上,能減少缺血性中風的發生比率、中風的嚴重度及死亡率。
對於亞洲族群,高風險非瓣膜性心房顫動使用香豆素且國際正常化比率( INR )控制在2到3中間,會比西方族群有更高的出血風險,所以有些亞洲族群的臨床試驗,顯示較低強度的抗凝血劑( INR < 2.5)比傳統強度的抗凝血劑治療( INR 2-3),不但有有效的中風預防且出血的安全性較高。甚至對於接受金屬瓣膜置換術後的台灣族群,將國際正常化比率( INR )控制於2以下,發現並沒有增加血栓事件的風險。因此許多醫生認為採取INR 1.5至2.5中間,來治療心房顫動的病患。如此按經驗法則來處理非瓣膜性心房顫動,對於台灣族群是否有效,目前沒有充分的研究証據。
為了進一步評估對於台灣族群高風險非瓣膜性心房顫動,真實世界使用抗血栓治療的情形及適當性,及是否使用較低強度的抗凝血劑和傳統強度的抗凝血劑治療有相同有效性。我們進行此回溯性研究,第一、我們想對於高風險非瓣膜性心房顫動,比較不同抗血栓治療,最後的臨床結果。第二、比較使用香豆素( warfarin )的高風險非瓣膜性心房顫動患者,將INR控制至少2和INR小於2,兩者間長期後果。吾人假設: 低強度的香豆素治療( INR < 2)和傳統強度香豆素治療( INR ≧ 2),對於預防中風有同樣效度,但低強度的香豆素治療能減少重大出血的風險。.
研究方法
我們回朔性收集於2001到2006年,在振興醫院心臟科連續815位非瓣膜性高風險心房顫動病患,依接受不同抗血栓治療,共分為三組,分別為香豆素(warfarin)治療組,抗血小板治療組及完全未接受抗血栓治療組 ,去比較三種不同治療方式的臨床後果,同時進一步比較低強度的香豆素治療( INR < 2)和傳統強度香豆素治療( INR ≧ 2)之效度及安全度.
結果:
我們一共收集815位有高風險之非瓣膜性心房顫動之病患,平均追蹤2.5年,其中有226位(28%)接受香豆素治療,512位(63%)接受抗血小板藥物治療,77位(9%)完全沒有接受任何抗血栓藥物治療,我們發現接受香豆素治療的所有事件發生(心臟血管死亡,缺血性中風,其他血栓性栓塞及重大出血)是每100人年有3.6,抗血小板藥物治療的所有事件發生是每100人年有6.0, 完全沒有接受任何抗血栓藥物治療的所有事件發生是每100人年有10.1 (p值=0.013),三組發生嚴重出血率相似 (p值=0.196). 在不同強度之香豆素治療( INR≧2及INR < 2),兩組間所有組合的缺血性中風無明顯差別,但接受傳統香豆素治療強度(INR≧2)比低強度(INR < 2)出現較多的出血事件.
結論:
於高風險非瓣膜性心房顫動之台灣病患,我們發現香豆素治療比抗血小板藥物及完全沒有接受任何抗血栓藥物治療,更能減少不好的臨床後果。,但低強度(INR < 2) 香豆素治療和傳統香豆素治療強度(INR≧2)有同樣效度去減少缺血性中風發生,但能減少主要出血的風險。另外香豆素之低使用率,代表仍有許多努力空間去改善對高風險非瓣膜性心房顫動之治療.

English Abstract
Backgrounds: Current practice guidelines for the management of patients with atrial fibrillation (AF) recommend that all patients with AF should receive long-term anticoagulant therapy with warfarin with a target international normalized ratio (INR) of 2.0 to 3.0 unless they are younger than 65 years old and have none of the risk factors for stroke, or unless there is a major contraindication to the use of warfarin. Warfarin therapy with a target international normalized ratio (INR) of 2.0 or greater in preventing stroke for high-risk patients with nonvalvular atrial fibrillation (AF) is very effective but is associated with a substantial risk of bleeding, especially in Asian people. The primary objective of this study is to determine whether warfarin treatment to achieve an INR of &lt; 2.0 (low-intensity) was as effective as an INR of > 2.0 (conventional-intensity) while resulting in less bleeding in Taiwanese patients.
Methods
We conducted a retrospective study in patients with AF and a high risk of stroke. The clinical outcomes of patients receiving different antithrombitic therapies were compared. The efficacy and safety of two different intensities of warfarin therapy with a target INR of &lt; 2.0 or a target INR of > 2.0 were also compared.
Results
A total of 815 consecutive patients were enrolled in the study and followed for a median of 2.5 years. Among them, 226 (28%) patients received warfarin therapy, 512 (63%) patients received antiplatelet therapy, and 77 (9%) patients were not taking any antithrombotic therapy. The overall event rates were 3.6 per 100 person-year with warfarin, 6.0 per 100 person-year with antiplatelet therapy, and 10.1 per 100 person-year with no treatment (P=0.013), while the rates of major bleeding were similar among the three groups (P=0.196). Although there was no significant difference in the frequency of composite efficacy endpoint between the two different intensities of warfarin therapy, patients receiving conventional-intensity warfarin experienced significantly more bleeding episodes than those who receiving low-intensity warfarin.
Conclusions
In high-risk Taiwanese patients with AF, our study demonstrated the benefits of warfarin therapy in reducing adverse clinical outcomes. However, a low-intensity warfarin is as effective as conventional-intensity warfarin and does reduce the risk of major bleeding. The underutilization of warfarin in the study patients indicates that there remains substantial room to improve implementation of warfarin therapy to those patients.

目錄

English Abstract---------------------------------------------------------------------------- 1
Chinese Abstract---------------------------------------------------------------------------- 3
List of Abbreviation------------------------------------------------------------------------- 5
Introduction----------------------------------------------------------------------------------- 6
Materials and Methods--------------------------------------------------------------------- 16
Study Patients---------------------------------------------------------------------------- 16
Antithrombotic Therapy---------------------------------------------------------------- 17
Data Collection--------------------------------------------------------------------------- 17
Statistical Analysis---------------------------------------------------------------------- 18
Results----------------------------------------------------------------------------------------- 20
Discussion------------------------------------------------------------------------------------- 23
Conclusions----------------------------------------------------------------------------------- 27
Perspectives---------------------------------------------------------------------------------- 27
References------------------------------------------------------------------------------------ 29
Figures and Tables-------------------------------------------------------------------------- 39

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