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研究生： 曹可欣
Tsao, Ke-Hsin
論文名稱： 心衰竭病患使用Spironolactone與減少心房顫動發生之探討
Relationship between Atrial Fibrillation and Use of Spironolactone in Heart Failure Patients
指導教授： 林立人
Lin, Li-Jen
高雅慧
Yang, Yea-Huei Kao
學位類別： 碩士
Master
系所名稱： 醫學院 - 臨床藥學研究所
Institute of Clinical Pharmacy
論文出版年： 2009
畢業學年度： 97
語文別： 中文
論文頁數： 100
中文關鍵詞： 健保資料庫 、處方型態 、心房顫動 、心衰竭
外文關鍵詞： prescribing pattern, spironolactone, heart failure, atrial fibrillation
相關次數： 點閱：180  下載：3 
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    • 研究背景
    心衰竭病患發生心房顫動的危險性比無心衰竭病患高出4-6倍。一旦發生心房顫動，將增加2-7倍的中風發生率，在心衰竭病患更增加2-3倍的死亡率。有研究指出，心衰竭病患使用spironolactone併用傳統療法，可以減少心律不整之發生。本研究之目的除了探討在實際臨床使用中，使用spironolactone與心房顫動發生之相關性，亦將提供國內心臟衰竭治療之藥品處方型態，探討在臺灣心衰竭準則建議治療是否落實於實際臨床使用。

    研究方法
    利用2000年-2004年未抽樣之全民健康保險資料申報檔，針對2001年1月1日至2003年12月31日期間，取樣門診或住院診斷碼出現心衰竭診斷且年齡大於65歲(含)的病患。首先，分析納入日期90天內之藥品處方型態，之後進行一個嵌入在心衰竭世代研究的心房顫動病例-對照研究，兩組之間以年齡(± 5歲)、性別和納入時間為配對條件，每一個病例最多將配對到8個對照患者，使用條件式邏輯回歸，心血管用藥與疾病史為校正因子，分析心衰竭患者使用spironolactone與心房顫動發生之相關性。

    研究結果
    心衰竭世代研究共納入275,061位病患。心衰竭準則建議用藥中，利尿劑之總處方率最高(57%)，其餘依次為ACEIs/ARBs (49%)、β-blockers (32%)、digitalis glycosides (25%)，spironolactone的處方率僅佔9%。心衰竭世代研究中，發生心房顫動之9,969位病例與70,679名對照患者完成配對，加以分析spirnolactone曝露程度之影響。指標日期前180天內，spironolactone曝露程度過低者將等同未曾處方者，歸類為非曝露者；而曝露組再區分為現正曝露組以及近期曝露組。以多變項邏輯回歸分析，結果顯示指標日期前180天內，與spironolactone非曝露組相較，近期曝露組對心房顫動之發生並沒有影響，而現正曝露則可明顯減少心房顫動發生之風險( p < 0.01)。進一步分析發現spironolactone之累積劑量達到心衰竭建議治療劑量的一半(30個定義每日劑量，相當於180天內每日平均劑量12.5 mg) 以及180天內處方天數達90天以上者，皆可有效減少心房顫動發生之風險。

    結論
    依據ACC/AHA 心衰竭治療準則(2005)，臺灣之心衰竭病患並未接受適當的心衰竭治療。雖然處方率與同時期之國外研究相近，未來需要更多研究分析國內心衰竭準則建議用藥之處方率與疾病預後之相關性，以評估臺灣心衰竭治療之成效。
    心衰竭病患使用spironolactone與其心房顫動之發生，和spironolactone的曝露量有關。使用spironolactone連續達90天以上或累積劑量達30個定義每日劑量(相當於180天內每日平均劑量12.5 mg) 以上，可減少心衰竭病患發生心房顫動之風險。因此，建議心衰竭病患在沒有禁忌症的前提之下，皆應該使用spironolactone進一步減少心房顫動之發生。

    Background
    Heart failure (HF) increases the risk of atrial fibrillation (AF) 4-6 fold. Compared with patients without AF, the risk of stroke of AF patients will increase 2-7 folds. The mortality of HF patients would even higher while they developed AF. Although clinical consensus suggested that using spironolactone with conventional therapy may decrease AF in HF patients, the clinical data are still limited. The aims of this study were to evaluate the relationship between AF and use of spironolactone in HF patients, and to provide prescribing pattern of HF treatment in Taiwan to examine the guideline adherence in clinical practice.

    Methods
    We conducted a case-control study nested in the study of HF patients who were documented with HF diagnosis in ambulatory or inpatient records and were older than 65 years during 1 January 2001 and 31 December 2003 using non- sampled National Health Insurance Research Database (NHIRD). Prescription rates were examined within 90 days after enrollment.
    Then we excluded patients according to exclusion criteria and assigned patients with low extent of exposure to spironolactone non-exposure group；exposure group was further divided to current and recent exposure group. A case was defined as a HF patient who developed AF during follow-up. Each case of AF was matched with up to 8 control patients by age(± 5)、gender and the time of enrollment. Conditional logistic regression was performed to identify the relationship between AF and use of spironolactone.

    Results
    In the HF study, we enrolled 275,061 HF patients (52 % women) with mean age 76 years. Diuretics were prescribed most frequently (57 %), following ACEIs/ARBs (49 %) 、β-blockers (32 %) and digitalis glycosides (25 %). Spironolactone was the least prescribed drug (9 %).
    During follow-up, total 80,648 patients were matched (case：9,969，control：70,679). Compared with non-exposure group, recent exposure group had no effect on the risk of AF while current exposure group was showed to significantly reduce the risk of AF ( p < 0.01). For the 180-day period before the index date, spironolactone user with cumulated dose between 30 - 120 DDD or with medication possession rate (MPR) ≥ 0.5 would both significantly reduce the risk of AF.

    Conclusions
    In Taiwan, evidence-based treatments which reduce morbidity and mortality were underused in HF patients.
    The relationship between spironolactone use and AF was based on the spironolactone’s extent of exposure. Using spironolactone for at least 90 days or 30 DDD (equal to mean daily dose 12.5 mg in 180 days) may reduce the risk of AF in HF patients. It’s recommended that all HF patients who are without contraindication should use spironolactone to further reduce the risk of AF.

    第一篇 心衰竭病患使用Spironolactone 與減少心房顫動發生之探討................. 1 第一章 研究背景...................................................................................................... 1 第二章 文獻回顧...................................................................................................... 2 第一節 心衰竭與心房顫動之疾病簡介.......................................................... 2 2.1.1 心衰竭............................................................................................ 2 2.1.1.1 流行病學....................................................................... 2 2.1.1.2 心衰竭疾病特性及分級............................................... 4 2.1.1.3 心衰竭之準則建議治療............................................... 6 2.1.1.4 心衰竭治療之藥物流行病學....................................... 13 2.1.2 心房顫動........................................................................................ 18 2.1.2.1 心房顫動分類............................................................... 18 2.1.2.2 流行病學....................................................................... 19 2.1.2.3 致病機轉....................................................................... 20 第二節 心衰竭與心房顫動之相關性.............................................................. 22 2.2.1 流行病學........................................................................................ 22 2.2.2 心衰竭病患發生心房顫動對預後之影響.................................... 23 2.2.3 心衰竭病患發生心房顫動之致病機轉........................................ 24 2.2.3.1 心房纖維化................................................................... 24 2.2.3.2 Aldosterone 在心房纖維化的角色.............................. 26 第三節 使用Spironolactone 與減少心房顫動發生之探討............................ 29 第三章 研究目的...................................................................................................... 32 第四章 研究方法...................................................................................................... 33 第一節 研究設計................................................................................................ 33 4.1.1 研究類型........................................................................................ 33 4.1.2 研究材料與工具............................................................................ 33 4.1.3 研究對象........................................................................................ 34 4.1.3.1 納入條件....................................................................... 34 4.1.3.2 排除條件....................................................................... 34 第二節 研究變項及操作定義說明.................................................................... 35 4.2.1 研究名詞定義................................................................................ 35 4.2.2 研究變項定義................................................................................ 37 第三節 研究流程.............................................................................................. 40 4.3.1 檔案檢查與串聯.......................................................................... 40 4.3.2 資料處理流程.............................................................................. 41 VIII 第四節 統計分析.............................................................................................. 42 4.4.1 統計模式設定.............................................................................. 42 4.4.2 資料分析方法.............................................................................. 42 第五章 研究結果...................................................................................................... 44 第一節 處方型態分析.................................................................................... 44 5.1.1 病患基本特性分布...................................................................... 44 5.1.2 心衰竭治療之藥品處方型態...................................................... 44 第二節 使用Spironolactone 與心房顫動發生之相關性分析........................ 51 5.2.1 共病症對心房顫動發生之影響.................................................. 52 5.2.2 心血管用藥對心房顫動發生之影響.......................................... 56 5.2.3 Spironolactone 對心房顫動發生之影響..................................... 60 第六章 研究討論...................................................................................................... 64 第一節 心衰竭治療之處方型態分析.............................................................. 64 6.1.1 研究族群人口特性...................................................................... 64 6.1.2 與Jhund 等人之研究的比較....................................................... 67 第二節 使用Spironolactone 與減少心房顫動發生之相關性........................ 70 6.2.1 共病症對心房顫動發生之影響.................................................. 70 6.2.2 心血管用藥對心房顫動發生之影響.......................................... 71 6.2.3 Spironolactone 對心房顫動發生之影響..................................... 72 第三節 研究限制.............................................................................................. 75 第七章 結論與建議.................................................................................................. 76 第二篇 臨床藥事服務 – Amiodarone(臟得樂)之用藥衛教.................................... 77 第一章 服務緣起........................................................................................................ 77 第二章 服務方法........................................................................................................ 78 第一節 服務對象.............................................................................................. 78 第二節 服務材料.............................................................................................. 78 第三節 服務流程.............................................................................................. 79 第三章 服務結果........................................................................................................ 84 第一節 病患特性.............................................................................................. 84 第二節 交互作用檢視結果.............................................................................. 84 第三節 Amiodarone 藥品使用認知評估......................................................... 84 第四節 衛教結果.............................................................................................. 85 第四章 心得與建議.................................................................................................... 89 第一節 衛教需求............................................................................................. 89 第二節 良好溝通............................................................................................. 90 第三節 經驗分享—副作用之解說................................................................. 90 第四節 結語..................................................................................................... 93 參考文獻...................................................................................................................... 95

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