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研究生:趙必暉
研究生(外文):Pi-huei Chao
論文名稱:血管張力素轉換酶抑制劑(ACEI)與血管張力素受體阻斷劑(ARB)於高血壓患者中風預防效果之探討
論文名稱(外文):Angiotensin-converting enzyme inhibitor or Angiotensin receptor blocker in preventing stroke among hypertension patients
指導教授:高雅慧高雅慧引用關係葉鳳英葉鳳英引用關係
指導教授(外文):Yea-huei Yang KaoPheng-ying Yeh
學位類別:碩士
校院名稱:國立成功大學
系所名稱:臨床藥學研究所
學門:醫藥衛生學門
學類:藥學學類
論文種類:學術論文
論文出版年:2009
畢業學年度:97
語文別:中文
論文頁數:81
中文關鍵詞:腦中風血管張力素轉換酶抑制劑血管張力素受體阻斷劑
外文關鍵詞:ACE inhibitorARBstrokehypertensionpopulation based study
相關次數:
  • 被引用被引用:1
  • 點閱點閱:1079
  • 評分評分:
  • 下載下載:134
  • 收藏至我的研究室書目清單書目收藏:2
研究背景:
腦中風是一個相當令人害怕的疾病,不僅造成病患死亡,即使是存活者,也常常導致肢體障礙、意識障礙以及行為能力喪失等。世界上每年約有550萬人死於腦中風;在台灣,預估每年有1.3萬人死於腦中風。不論國內、外,腦中風始終排名在十大死因的前三位。
腦中風的危險因子包含兩大類:可改變(如:高血壓)及不可改變的危險因子(如:性別)兩大類。其中,高血壓是最主要的腦中風危險因子。大約有70%的腦中風病患本身都有高血壓的病史,因此對於預防腦中風發生,控制血壓是最重要的關鍵。
所有降血壓藥都可以藉由血壓的控制達到有效預防腦中風的發生,其中ACEI及ARB是最常用的降血壓藥之一。除了血壓的控制外,在某些臨床試驗中發現ACEI及ARB可以減少目標器官的損傷。在近期的試驗中發現,對於預防腦中風的發生,ARB似乎比起ACEI有更多的優勢。出現這種結果的原因可能來自於兩種藥品在藥理機轉上的差異。
研究目標:
比較ACEI與ARB在高血壓患者對中風預防之成效。
研究方法:
本研究為回溯性世代研究。資料來源為中央健保局資料庫1996~2006的百萬人抽樣檔。本研究之研究對象為1998~2005年間曾經被診斷為高血壓且有使用ACEI或ARB的病患。曾經中風、過去3個月曾經使用ACEI或ARB、年齡小於45歲或是同時處方ACEI和ARB者予以排除。主要研究事件為患者因為中風而住院。本研究使用存活分析方法來分析結果。

研究結果:
總共有34,203人符合納入及排除條件進入本研究;其中ACEI組有22,636人,ARB組有9,648人。兩組的糖尿病患都約佔30%,高血脂(30% vs. 38.6%) 和缺血性心臟病(26.7% vs. 33.6%)都是ARB組比較多。ACEI組中共發生了382件腦中風事件,ARB組則有144件;缺血性腦中風約佔70%。ARB組的腦中風發生比例比較低(每1000人年發生腦中風事件數:12.35vs. 9.54 )。在COX迴歸分析中,ARB組有較低的腦中風發生風險([HR] 1.35, 95% Cl 1.11-1.64)。
結論:
在本研究中發現,高血壓的族群中,相較於ACEI的使用者,ARB的使用者發生腦中風的機率下降。
本研究仍有一些限制,未來需要其他研究以證實ARB的優勢。
關鍵字:血管張力素受體阻斷劑、血管張力素轉換酶抑制劑、腦中風
Background
Stroke is a scaring disease which may cause debilitating consequences, negative impact of quality of life, a loss of independent and even death of patients. Each year, 5.5 million people die as result of a stroke across the world and about 13thousand people in Taiwan. No weather Taiwan or the whole world, stroke is the third leading death and the major health care problem.
Risk factors of stroke include nonmodifiable (sex, age, etc.) and modifiable (eg, hypertension, diabetes mellitus) factors. Of modifiable factors, hypertension is a major one and about 70% of stroke patients have it, so control of hypertension is a key point of stroke prevention.
All antihypertensive agents can reduce the risk of stroke which by the effect of blood pressure reduction and angiotensin-converting enzyme inhibitor (ACEI)/ angiotensin ll receptor blocker (ARB) are one of them usually used. According some clinical trials, the both them are effective in reducing the risk of target organ damage such as heart failure and renal failure. These kinds of effect were thought that out of blood pressure control. In recent trials, these phenomena also are found in risk reduction of stroke. In view of different mechanism of ACEI and ARB, there were a few trials to compare these two classes of drugs. The aim of this study is to compare these two classes of drugs and focus on stroke prevention.
Method
A retrospective cohort study was conducted using the Nation Health Insurance (NHI) claims database spanning the period from 1996 to 2006 representing 1 million sampling from whole population in Taiwan. The study subjects included patients who had hypertension diagnosis and initiated use of ACEI/ARB from 1998 to 2005. Those with a history of stroke, previous use of ACEI/ARB within 3 months, younger than 45 years, or received these two drugs simultaneously were excluded. The primary outcome was hospitalized due to stroke after the start of follow up. The results were analyzed using Cox proportional hazard regression.
Result
Total 32,284 patients confirmed with the inclusion and exclusion criteria in the end of study; 22,636 patients in ACEI group and 9,648 patients in ARB group. About 30% of patients have diabetes mellitus and more dyslipdemia (30% vs. 38.6%) and cardiac vascular disease (26.7% vs. 33.6%) patients in ARB group. Stroke events accounted for 382 patients in ACEI group and 144 patients in the other group, about 70% of them which were ischemia stroke. Patients receiving ARB had a lower risk for the primary outcome during follow-up (12.35 vs. 9.54 events per 1000 patient-years at risk). In COX regression model, it also show the same result (multivariable adjusted hazard ratio [HR] 1.35, 95% Cl 1.11-1.64).
Conclusion
Result of this retrospective cohort study shows that the use of ARB may reduce the risk of stroke comparing with ACEI. But some limitations were in this study, more studies were needed to prove this result.
Keywords: ACE inhibitor、ARB、stroke、hypertension、population based study
中文摘要 i
Abstract iii
誌謝 v
目錄 vii
表目錄 xi
圖目錄 xii
第一篇、血管張力素轉換酶抑制劑(ACEI)與血管張力素受體阻斷劑(ARB)於高血壓患者中風預防效果之探討 1
第一章 、研究緣起 1
第二章 、文獻回顧 3
第一節 腦血管疾病 3
2.1.1 腦血管疾病盛行率與發生率 3
2.1.2 腦中風的分類 4
2.1.3 腦血管疾病相關危險因子 5
第二節 高血壓與腦中風疾病 9
2.2.1 高血壓盛行率 9
2.2.2 高血壓的定義 10
2.2.3 高血壓與腦血管疾病的關係 11
第三節 ACEI 和ARB的作用機轉 12
2.3.1 主要作用機轉 12
2.3.2 ARB 與ACEI對於中風保護效果機轉上的差異 12
第四節 ACEI與ARB中風保護效果之臨床試驗 15
2.4.1 ACEI 15
2.4.2 ARB 16
2.4.3 ACEI vs. ARB 17
第三章 、研究目的 20
第四章 、研究方法 21
第一節 研究設計 21
4.1.1 21
4.1.2 研究材料與工具 21
4.1.3 納入對象 22
4.1.4 排除條件 22
第二節 研究變項及操作定義 24
4.2.1 研究分組定義 24
4.2.2 用藥持續性 24
4.2.3 研究終點 24
4.2.4 疾病共變因子 26
合併使用藥品 27
第三節 資料處理流程 28
4.3.1 檔案串聯 28
4.3.2 研究流程 29
第四節 統計方法 31
4.4.1 統計工具 31
4.4.2 統計模式設定 31
4.4.3 資料分析方法 31
第五章 研究結果 33
第一節 基本資料 33
5.1.1 研究流程 33
5.1.2 病患基本資料 36
第二節 腦中風事件與其影響因子之關聯性 39
5.2.1 ACEI/ARB與腦中風之關聯 39
5.2.2 其他影響因子與腦中風之關聯性 39
第三節 腦中風事件與ACEI/ARB使用之次分析 44
5.3.1 次分析:排除心律不整及心衰竭病患 44
5.3.2 次分析:糖尿病患者 46
5.3.3 次分析:缺血性心臟病患者 49
第六章 、 討論 52
第一節 基本資料 52
6.1.1 高血壓與腦中風 52
6.1.2 病患基本資料 53
第二節 腦中風事件與其影響因子之關聯性探討 55
6.2.1 ACEI/ARB與腦中風之關聯性探討 55
6.2.2 其他影響因子之探討 58
第三節 用藥順從性 60
第四節 腦中風事件與ACEI/ARB使用之次分析 61
6.4.1 次分析;排除心律不整及心衰竭病患 61
第五節 研究設計討論 62
第七章 研究限制 64
第八章 結論與建議 65
第二篇、臨床藥事服務-高血壓病患中風預防衛教 66
第一章 衛教背景 66
第二章 衛教方式 67
第三章 衛教結果 68
第四章 心得與討論 71
參考文獻 76
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