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研究生： 鄧軒婷
Teng, Hsuan-ting
論文名稱： 慢性腎病患者長期使用低劑量Aspirin之安全性評估
The safety of low dose aspirin in chronic kidney disease patients
指導教授： 蔡瑞真
Tsai, Jui-Chen
吳安邦
Wu, An-Bang
廖麗香
Liao, Li-Hsiang
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： 2008
畢業學年度： 96
語文別： 中文
論文頁數： 107
中文關鍵詞： 腎功能 、出血 、低劑量阿斯匹靈 、死亡率 、血清肌酸酐 、慢性腎病
外文關鍵詞： serum createnine, bleeding, mortality, low-dose aspirin, renal fuction, chronic kidney disease
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    • 背景：
    慢性腎病 (chronic kidney disease，CKD )成為近年來全球性的公共衛生問題，其盛行率和發生率逐年持續增加當中。此外，在近年的流行病學研究中，慢性腎病已被視為心血管疾病的重要危險因子。且慢性腎病患者易伴隨高血壓、糖尿病及心血管疾病，所以不論是已經發生心血管事件或因為具有高危險因子都可能需要使用低劑量阿斯匹靈（ Aspirin ）來減少或預防心血管疾病的發生。
    目前的臨床研究不論是一般的止痛劑量或是低劑量之Aspirin，對於腎功能影響的結果都不盡相同。而且許多大型的心血管疾病的臨床試驗都排除了慢性腎病的族群，故對於慢性腎病族群長期使用低劑量Aspirin對腎臟所產生的影響及出血事件都還需要評估。
    研究目的：
    評估低劑量Aspirin對於慢性腎病患者腎功能及所有原因死亡率之影響。次要評估低劑量Aspirin在慢性腎病患者出血危險的影響。
    研究方法：
    本研究為回溯性世代觀察研究，以2003/1/1至2003/12/31門診診斷碼為Chronic renal failure或Chronic renal insufficiency之病患為研究對象，以病例回顧為研究工具。將這些研究對象依有無使用Aspirin分成(1)治療組:第一次診斷為CKD ( serum creatinine, SCr ≧ 1.5 mg/dL )後連續使用 Aspirin 100mg/day 大於等於6個月。(2)對照組 :第一次診斷為CKD後沒有使用 Aspirin 任一劑型和劑量。追蹤病人至2007年12月為止。主要評估指標包括：（1）腎功能評估指標。（2）評估所有原因死亡率。次要評估指標為出血事件。統計分析方法採用存活率或事件未發生率( survival or event-free analysis )顯示慢性腎病患者達到評估指標時的存活情形。
    研究結果：
    共有117位病人納入分析，其中Aspirin組有57人，對照組有60人。由符合慢性腎病的納入標準之時間開始觀察，結果顯示使用低劑量Aspirin較對照組延緩腎功能惡化；從開始使用Aspirin之時間來觀察，結果顯示低劑量Aspirin的使用並無對於腎臟有惡化的影響。追蹤期間Aspirin的使用可以降低所有原因死亡率65％。對於使用Aspirin可能造成出血事件的分析結果，不論在嚴重出血或輕微出血事件中，治療組和對照組均無顯著差異。排除有胃潰瘍病史的病患後進行分析，發現在輕微出血事件中治療組則顯著高於對照組。
    結論：
    慢性腎病患者使用低劑量Aspirin在長期使用下有腎臟保護效果，且對於所有原因的死亡率有顯著的降低。此外，在出血事件方面，低劑量的Aspirin沒有增加嚴重出血的危險，但可能增加輕微出血的危險。

    Background：
    Chronic kidney disease (CKD) is becoming a worldwide health problem and the prevalence and incidence are growing fast. CKD is associated with an increased risk of adverse cardiovascular outcomes and is considered a cardiovascular disease (CVD) risk equivalent. Long-term low-dose aspirin therapy reduces the risk of subsequent myocardial infarction (MI), stroke, and vascular death among patients with a wide range of prior manifestations of cardiovascular disease.
    According to clinical studies, patients with CKD have been largely excluded from clinical trials of patients with coronary artery disease. The influences of aspirin are inconsistent in CKD. There is still no good evidence of the safety of using low dose aspirin in CKD patients.
    Objective：
    To evaluate the effects of low-dose aspirin on the renal function, all causes of mortality and bleeding events of CKD patients.
    Method：
    We enrolled CKD patients of serum creatinine (SCr) ≧ 1.5 mg/dL at entry of the study in National Cheng Kung University Hospital from Jan 2003 to Dec 2003. The patients were grouped into aspirin group and control group. They were followed these patients until Dec, 2007.
    Main outcome measures：
    The primary outcome was defined as a 50% increase of SCr or initiation of dialysis therapy and all causes of mortality. The secondary outcome was the bleeding events.
    Results：
    Among 117 CKD patients, 57 were Aspirin group and 60 were control group. Low-dose aspirin significantly reduced renal impairment and all-cause of mortality rate. About major and minor bleeding, there are no significant differences between Aspirin and control group. After rule out patients with history of GI ulcer, major bleeding is no significant difference between Aspirin and control group (1：2, p=0.488）; but minor bleeding in Aspirin group is significantly higher than control group ( 11：3, p=0.036）.
    Conclusion:
    Long-term use of low-dose aspirin had renal protection and reduced all-cause mortality in chronic kidney disease patients. There was no excess of major bleeds, but minor bleeding was significantly increased.

    中文摘要 i Abstract v 表目錄 ix 圖目錄 x 第一篇、慢性腎病患者長期使用低劑量Aspirin之安全性評估 1 第一章 研究背景 1 第二章 文獻回顧 4 第一節 台灣對於慢性腎病之低警覺性 4 第二節 慢性腎病之流行病學 8 第三節 慢性腎病之簡介 9 2.3.1 慢性腎病之臨床表徵 11 2.3.2 腎功能 13 第四節 慢性腎病和心血管疾病 14 第五節 Aspirin在心血管疾病的角色 18 2.5.1 初級預防（ Primary prevention ） 19 2.5.2 次級預防（ Secondary prevention ） 22 2.5.3 慢性腎病之族群在心血管疾病的臨床試驗之研究 24 第六節 Aspirin對腎功能的影響 25 2.6.1 腎血流量的調節 25 2.6.2 Aspirin影響腎功能之學理理論 26 2.6.3 Aspirin影響腎功能之臨床研究 28 第七節 Aspirin在腎功能不全病患之出血危險 34 第三章 研究目的 37 第四章 研究方法 38 第一節 研究設計 38 4.1.1 研究類型 38 4.1.2 研究時間與納入對象 38 4.1.3 排除標準 38 第二節 研究流程 39 第三節 研究變項及評估指標之定義 42 4.3.1 各研究變項之定義 42 4.3.2 評估指標之定義 43 第四節 統計方法 44 4.4.1 統計模式設定 44 4.4.2 資料分析方法 44 4.4.3 資料管理軟體與統計分析軟體 46 第五章 研究結果 47 第一節 Aspirin對腎功能影響的結果 47 5.1.1 病患基本資料 47 5.1.2 病患之其他合併症與其他併用藥品 48 5.1.3 從符合慢性腎病的納入標準開始觀察 53 5.1.4 從開始使用Aspirin開始觀察 54 第二節 所有原因死亡率 62 5.2.1 病患基本資料、合併症及其他併用藥物 62 5.2.2 存活分析 67 第三節 次要評估指標（出血事件）之分析 71 第六章 討論 73 第一節 腎功能評估指標 73 第二節 所有原因死亡 80 第三節 出血事件 84 第四節 研究限制 85 第五節 未來研究方向 85 第七章 結語 86 第二篇 臨床藥事服務 87 第一章 目的 87 第二章 臨床服務進行方式 89 第三章 臨床服務執行結果 90 第一節 病患特性 90 第二節 病患用藥特性 90 第三節 衛教成效 91 3.3.1 用藥情形 91 3.3.2 衛教前後病患用藥知識測驗 91 3.3.3 服藥順從率 91 第四章 討論與結語 99 參考文獻 100

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