臺灣博碩士論文加值系統

研究背景：健保局於2002年7月實施(西醫)醫院總額預算制度，期望控制醫療費用的快速成長。因為預算固定，若醫院之醫療資源使用愈多，則對醫院經營愈不利。因此，如何在醫療資源有限的情況下，減少醫院藥品的重覆，同時又能對病患維持適當的照顧，便成為醫院經營者的一個重要課題。對此，國內醫院經營者可採用「限制選擇藥品範圍」的方式來節制藥費，而美國則在1993年發展了「治療取代」做為管理處方集的一種方式。「治療取代」是指：在醫院藥事委員會的同意下，藥師從具有治療相等性的同類藥品中，選擇一個最適當的藥品，以取代醫師所開的其他同類藥品。本研究即引用「治療取代」的概念，發展方法學給醫院藥師參考及運用，期望使用較符合成本效益的藥品，以控制醫院的醫療支出及藥費成長率。

研究目的：本研究的目的在於發展方法學，以statins為例，從六個具有治療相等性的statins中，選擇較符合成本效益的statin(s)以取代其他statins。

研究方法：運用成本效果分析的方法，比較六個statins之醫療總成本及療效結果，以選出較符合成本效益的statin(s)。成本之計算乃利用健保資料庫分析，取得混合型血脂異常及原發性高膽固醇血症病人使用單項statin六個月之門診相關醫療花費，包括藥費、診察費、檢驗費及藥事服務費。療效結果則是參考已發表的statins類藥品之完整系統性回顧報告書，進行本研究所需之相關數據的萃取及整合。取得本研究目標族群使用各statin長達六個月之門診總成本及相對應的療效後，再以Karlsson等人發表的決策分析流程進行六個statin之成本效果分析比較。

研究結果：成本分析的結果顯示，每人六個月門診平均總成本最低的是rosuvastatin (NT$6,850)，最高的則是pravastatin (NT$9,078)。在療效數據方面，從納入的60篇文獻整合結果發現，「降低LDL-C平均濃度百分比」、「降低LDL-C/HDL-C平均比值百分比」以及「達到ATP Ⅲ所建議之LDL-C治療目標的平均人數百分比」三個療效指標上，效果最好的皆是rosuvastatin，最差的皆是fluvastatin。由成本效果分析之結果發現：與其他五個statins比較，rosuvastatin乃是效果最好且門診總成本最低(最佔優勢)的statin。Rosuvastatin相較於沒有治療，每讓一名病人多降低LDL-C平均濃度一個百分比約需花費NT$153元。

結論：本研究經由成本效果分析之結果，選出最佔優勢(dominant)的statin為rosuvastatin。建議醫院藥事委員會在混合型血脂異常及原發性高膽固醇血症兩個適應症下，以rosuvastatin取代其他statins，可讓藥品的使用成本最低，並讓病人群獲得最大的整體效益。

Background: In order to control the rising health care costs, the Bureau of National Health Insurance (BNHI) in Taiwan implemented the hospital global budget system in July 1, 2002. When the budget is fixed, the more medical resources the hospital is using, the worse of the financial situation will be. Therefore, under limited medical resources, to restrict number of drugs used in the formulary or reduce the number of drugs doctor can choose may be a method for the hospital manager. In the United States, the therapeutic interchange program was used in the formulary management in 1993. Therapeutic interchange is defined as under approval of P&T Committee, pharmacists substitute and dispense a drug that is therapeutically equivalent to but chemically different from the drug originally prescribed by a physician. This study used the concept of therapeutic interchange and developed methodologies that can be used for pharmacist practice in the hospital setting to suggest physicians to use the most cost-effective drug among drugs which are therapeutically equivalent to contain medication and health care costs of the hospital.

Objective: To develope methodologies to select the most cost-effective statin among statins which are therapeutically equivalent to use in the hospital setting.

Methods: The study used the cost-effectiveness analysis to compare the health care costs and effectiveness of the six statins and recommend the most cost-effective statin among the six statins which are therapeutically equivalent. Direct medical costs were derived from BNHI claimed-database, including the cost of drugs, physician services, dispensing services and laboratory tests of the patients with mixed dyslipidemia or primary hypercholesterolemia. The time horizon is six months which starts from the first dispensing date of that specific statin for the naïve patients. The effectiveness was derived from the systematic review of statins which was published by Oregon Health and Science University. Subsequently, the decision rule algorithm of cost-effectiveness analysis established by Karlsson and Johanesson was adopted to determine the best choice of statin(s).

Results: With respect of the cost, rosuvastatin had the lowest cost of six months ambulatory care per patient (NT$6,850), whereas pravastatin had the highest (NT$9,078). Concerning the effectiveness, rosuvastatin was associated with the greatest effectiveness in terms of the reduction of LDL-C, LDL-C/HDL-C and the proportion of patients achieving the ATP Ⅲ LDL-C goal, whereas fluvastatin had the lowest effectiveness. In the base-case and sensitivity analysis, rosuvastatin dominate the other five statins. Compare to do-nothing, the incremental cost per additional 1% reduction in LDL-C was NT$153 for rosuvastatin.

Conclusion: Rosuvastatin dominates the other five statins because it is most effective and least costly. In order to minimize the total health care cost and maximize the aggregate effectiveness, we recommend that P&T committee uses rosuvastatin in stead of the other five statins for patients with mixed dyslipidemia or primary hypercholesterolemia.

Key words: therapeutic interchange, dyslipidemia, statin, cost-effectiveness analysis, claimed-database analysis

正文目錄
第一章 緒言 1
第一節 研究緣起 1
第二節 研究目的 3
第三節 研究問題 3
第四節 名詞解釋 3
壹、 血脂異常(Dyslipidemia)之介紹 3
貳、 台灣血脂異常之盛行率 7
參、 血脂異常之處理 9
肆、 成本結果分析(Cost-consequences analysis)與成本效果分析(Cost-effectiveness analysis) 11
第二章 文獻回顧 13
第一節 治療取代政策 13
第二節 從同類藥品中選擇最符合成本效益的藥品之方法學 17
壹、 Generalized cost-effectiveness analysis (GCEA) 17
貳、 Efficiency frontier 20
參、 Karlsson等人發表的決策分析流程 23
第三節 病人血中LDL-C濃度與病人未來發生心血管疾病的關係 24
第四節 國內statins類藥品之成本效果分析 24
第五節 國外statins類藥品之成本效果分析 26
壹、 Costa-Scharpla等人之藥物經濟學研究 26
貳、 Ohsfeldt等人之藥物經濟學研究 29
參、 Pinto等人之藥物經濟學研究 30
肆、 討論與結語 31
第三章 研究方法 37
第一節 分析所持立場(Perspective) 37
第二節 適應症與目標族群 37
第三節 研究藥品 38
第四節 研究分析時限(Time horizon) 39
第五節 研究模型之建立 39
第六節 資料來源 41
壹、 成本之測量與定價(Cost measurement and valuation) 41
貳、 療效結果之測量(Outcome measurement) 50
第七節 本研究之各項假設 55
第八節 資料處理與分析 56
壹、 分析軟體 56
貳、 基礎案例分析(Base-case analysis) 56
參、 敏感性分析(Sensitivity analysis) 67
第四章 研究結果 68
第一節 成本分析結果 68
壹、 Naïve病人群 68
貳、 目標族群(target population) 70
參、 Statins治療期間之門診醫療成本 74
第二節 療效數據之萃取及整合結果 91
壹、 篩選結果 91
貳、 數據萃取結果 94
參、 數據整合結果 94
第三節 成本效果分析結果 97
壹、 基礎案例分析結果 97
貳、 敏感性分析結果 102
第五章 研究討論 114
第一節 研究方法討論 114
第二節 研究結果討論 116
壹、 Statins之使用情況 116
貳、 療效結果(Outcome) 118
參、 研究結果 122
第三節 研究限制 123
壹、 以國外療效數據代替國內療效數據 123
貳、 沒有將住院醫療成本納入計算 123
參、 門診檢驗費有高估的可能 123
肆、 分析結果無法推論到心血管疾病之最終結果 124
第四節 應用層面討論 124
第五節 建議 125
第六節 未來研究方向 125
第六章 結論 126
參考文獻 127

『表』目錄
表 1：NCEP-ATP III對於血脂異常嚴重程度之分類 5
表 2：歐洲動脈硬化學會對於血脂異常之治療性分類 5
表 3：Fredrickson等人對於血脂異常之分類 6
表 4：國人各種年齡層之高血脂盛行率 8
表 5：ATP Ⅲ以LDL-C作為治療追蹤的目標，並評估病患動脈硬化疾病之危險因子，以決定治療之策略及目標 9
表 6：Statins類藥品標準劑量、最大劑量以及降LDL-C百分比 10
表 7：各statin之FDA核准適應症 15
表 8：依照GCEA之原則所排列出的「league table」 19
表 9：國外statins類藥品之成本效果分析─文獻內容整理 34
表 10：與statin治療相關之診療項目及支付點數 46
表 11：各項門診醫療成本之計算方式 48
表 12：步驟1，排除療效較低但成本較高(dominated)的藥品 57
表 13：步驟2-1，將療效較高的藥品跟前一個藥品相比，計算出ICER值 58
表 14：步驟2-2，將療效較低但ICER值較大的藥品(extended dominated)予以排除 59
表 15：步驟2-3，重新計算被留下來之藥品的ICER值 60
表 16：步驟3，將未被排除(undominated)的藥品排列出建議使用的先後順序 61
表 17：在不同預算總額下，建議使用的藥品及使用藥品之人數 63
表 18：利用Excel Solver所建立之模式求得「使用各藥的病人數」(Number of pt’s per treatment)，以獲得最大化的整體效益(Aggregate effectiveness) 64
表 19：Naïve病人所使用的降血脂藥品以及各藥品之使用人數 69
表 20：各statin之使用人數、每人平均理論用藥天數、實際擁有藥品天數及藥品擁有率(MPR) 70
表 21：符合納入條件之病人群的總人數、平均年齡及男性人數比例 72
表 22：符合納入條件之病人群的疾病概況 73
表 23：符合納入條件之病人群的住院率 75
表 24：各cohort每人平均門診總成本 77
表 25：各cohort之「每人平均門診總成本差異」之事後比較 79
表 26：各cohort之每人平均門診總成本及各門診醫療成本項目之金額 81
表 27：各cohort之每人平均門診藥費、總給藥天數及每日藥費 82
表 28：各cohort之每人平均門診診察費、使用次數及單次花費 83
表 29：使用lovastatin之病人群的每人平均門診檢驗費、使用次數及單次花費 84
表 30：各cohort之每人平均門診藥事服務費、使用次數及單次花費 84
表 31：各cohort之「每人平均門診藥費差異」之事後比較 86
表 32：隨著時間的增加，各cohort之使用人數百分比在各個「每日劑量」間分佈的變化 88
表 33：各statin之不同劑量的納入篇數及人數 93
表 34：不同statin在各劑量下的療效數據整合結果 96
表 35：各statin之成本效果分析的基礎案例分析結果—以LDL-C下降量(%)為療效指標 98
表 36：各statin之成本效果分析的基礎案例分析結果—以HDL-C上升量(%)為療效指標 99
表 37：各statin之成本效果分析的基礎案例分析結果—以LDL-C/HDL-C下降量(%)為療效指標 100
表 38：各statin之成本效果分析的基礎案例結果—以達到LDL-C治療目標人數(%)為療效指標 101
表 39：各statin之成本效果分析的敏感性分析結果—療效指標為LDL-C下降量(%)、每人平均門診總成本為95% C.I.的下限 104
表 40：各statin之成本效果分析的敏感性分析結果—療效指標為LDL-C下降量(%)、每人平均門診總成本為95% C.I.的上限 104
表 41：各statin之成本效果分析的敏感性分析結果—療效指標為HDL-C上升量(%)、每人平均門診總成本為95% C.I.的下限 105
表 42：各statin之成本效果分析的敏感性分析結果—療效指標為HDL-C上升量(%)、每人平均門診總成本為95% C.I.的上限 105
表 43：各statin之成本效果分析的敏感性分析結果—療效指標為LDL-C/HDL-C下降量(%)、每人平均門診總成本為95% C.I.的下限 106
表 44：各statin之成本效果分析的敏感性分析結果—療效指標為LDL-C/HDL-C下降量(%)、每人平均門診總成本為95% C.I.的上限 106
表 45：各statin之成本效果分析的敏感性分析結果—療效指標為達到LDL-C治療目標人數(%)、每人平均門診總成本為95% C.I.的下限 107
表 46：各statin之成本效果分析的敏感性分析結果—療效指標為達到LDL-C治療目標人數(%)、每人平均門診總成本為95% C.I.的上限 107
表 47：各statin之成本效果分析的敏感性分析結果—療效指標為LDL-C下降量(%)、rosuvastatin之每人平均門診總成本為95% C.I.的上限而其他五個statins之每人平均門診總成本為95% C.I.的下限 108
表 48：各statin之成本效果分析的敏感性分析結果—療效指標為HDL-C上升量(%)、rosuvastatin之每人平均門診總成本為95% C.I.的上限而其他五個statins之每人平均門診總成本為95% C.I.的下限 108
表 49：各statin之成本效果分析的敏感性分析結果—療效指標為LDL-C/HDL-C下降量(%)、rosuvastatin之每人平均門診總成本為95% C.I.的上限而其他五個statins之每人平均門診總成本為95% C.I.的下限 109
表 50：各statin之成本效果分析的敏感性結果—以達到LDL-C治療目標人數(%)為療效指標、rosuvastatin之每人平均門診總成本為95% C.I.的上限而其他五個statins之每人平均門診總成本為95% C.I.的下限 109
表 51：各statin之成本效果分析的敏感性分析結果—療效指標為LDL-C下降量(%)、療效數據為納入文獻中所萃取之療效數據的最小值 110
表 52：各statin之成本效果分析的敏感性分析結果—療效指標為LDL-C下降量(%)、療效數據為納入文獻中所萃取之療效數據的最大值 110
表 53：各statin之成本效果分析的敏感性分析結果—療效指標為HDL-C上升量(%)、療效數據為納入文獻中所萃取之療效數據的最小值 111
表 54：各statin之成本效果分析的敏感性分析結果—療效指標為HDL-C上升量(%)、療效數據為納入文獻中所萃取之療效數據的最大值 111
表 55：各statin之成本效果分析的敏感性分析結果—療效指標為LDL-C/HDL-C下降量(%)、療效數據為納入文獻中所萃取之療效數據的最小值 112
表 56：各statin之成本效果分析的敏感性分析結果—療效指標為LDL-C/HDL-C下降量(%)、療效數據為納入文獻中所萃取之療效數據的最大值 112
表 57：各statin之成本效果分析的敏感性分析結果—療效指標為達到LDL-C治療目標人數(%)、療效數據為納入文獻中所萃取之療效數據的最小值 113
表 58：各statin之成本效果分析的敏感性分析結果—療效指標為達到LDL-C治療目標人數(%)、療效數據為納入文獻中所萃取之療效數據的最大值 113
表 59：各statin於台灣臨床試驗之納入篇數及人數 120
表 60：不同statin於台灣臨床試驗的療效數據整合結果 121

『圖』目錄
圖 1：依照GCEA之原則所畫出的「Cost-Effectiveness plane」 18
圖 2：以efficiency frontier幫助決策者決定療效較優異之新治療方式的給付上限值 22
圖 3：本研究之研究模型 40
圖 4：從資料庫中找出與statins治療相關的門診醫療紀錄之示意圖 47
圖 5：在不同預算總額下，建議選擇的藥品 62
圖 6：各藥品之ICER值，以及選用各藥品時，病人群所能得到的整體療效 66
圖 7：篩選流程(以lovastatin為例) 71
圖 8：各cohort之門診總成本的分佈 76
圖 9：各cohort之每人平均門診總成本及95% C.I. 78
圖 10：各項門診醫療成本佔門診總成本的百分比 80
圖 11：各cohort的各種「每日劑量」之使用人數百分比 89
圖 12：比較各「使用人數百分比較高之每日劑量」的「門診每日藥費」(括號內的數字為各個每日劑量之「使用人數百分比」) 90
圖 13：文獻篩選流程 91
圖 14：各statin之平均每人180天之門診總成本及LDL-C下降量(%) 98
圖 15：各statin之平均每人180天之門診成本及HDL-C上升量(%) 99
圖 16：各statin之平均每人180天之門診成本及LDL-C/HDL-C下降量(%) 100
圖 17：各statin之平均每人180天之門診成本及達到LDL-C治療目標的人數(%) 101

『附錄』目錄
附錄 一、Drug Class Review on HMG-CoA Reductase Inhibitors (Statins), Final Report.: Oregon Evidence-based Practice Center, Oregon Health & Science University之文獻回顧方法
附錄 二、持續使用一種statin治療(且沒有服用其他降血脂類藥品)長達三個月以上的病人群之總人數、平均年齡及男性人數比例
附錄 三、持續使用一種statin治療(且沒有服用其他降血脂類藥品)長達三個月以上的病人群之常見起始劑量及使用各statin之概況
附錄 四、持續使用一種statin治療(且沒有服用其他降血脂類藥品)分別長達三個月(90天)、六個月(180天)、九個月(270天)及十二個月(365天)以上的病人群之人數
附錄 五：各cohort所使用之statin的商品名及其處方出現次數百分比
附錄 六、病人性別與statins種類在門診總成本之各細格平均數與邊緣平均數
附錄 七、各cohort之每人平均門診檢驗費、使用次數及單次花費
附錄 八、納入文獻之整理
附錄 九、納入文獻之療效數據整理
附錄 十、敏感性分析結果

1.Yang BM, Bae EY, Kim J. Economic evaluation and pharmaceutical reimbursement reform in South Korea's National Health Insurance. Health Affairs. 2008;27:179-187.
2.紀櫻珍，林裕能，王美玉等人。臺北市立醫院自主管理之初步評估。北市醫學雜誌。2005;2:61-70。
3.吳帆，楊耀山，醫院自主管理指標資訊系統建構--以中部某區域醫院為例。醫務管理期刊。2003;4:59-76。
4.謝幸燕，呂慶祥，范保羅。總額預算制與醫院的藥品處方管理策略。 http://sts.nthu.edu.tw/scholarlist_files/31_%C2%E5%B0%7C%AA%BA%C3%C4%AB~%B3B%A4%E8%BA%DE%B2z%B5%A6%B2%A4.pdf. Accessed May 2, 2009.
5.中央健康保險局。 http://www.nhi.gov.tw/webdata/webdata.asp?menu=1&menu_id=8&webdata_id=2046&WD_ID=525. Accessed April 9, 2009.
6.American College of Clinical Pharmacy. ACCP position statement :guidelines for therapeutic interchange. Pharmacotherapy. 1993;13:252-256.
7.Gray T, Bertch K, Galt K, et al. American College of Clinical Pharmacy. ACCP Position Statement .Guidelines for therapeutic interchange-2004. Pharmacotherapy. 2005;25:1666-1680.
8.Ballantyne CM, James H. O'Keefe J, Antonio M. Gotto J. DYSLIPIDEMIA ESSENTIALS. Third ed. Bangkok: iGroup Press; 2007.
9.Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation. 2002;106:3143-3421.
10.丁予安，何橈通，宋育民等人。高血脂防治手冊：國人血脂異常診療及預防指引。台北: 行政院衛生署國民健康局; 2003。
11.DiPiro JT. Pharmacotherapy: a pathophysiologic approach. 7th ed. New York: McGraw-Hill; 2008.
12.Harper CR, Jacobson TA. New perspectives on the management of low levels of high-density lipoprotein cholesterol. Arch Intern Med. 1999;159:1049-1057.
13.「全民健康保險藥品給付規定」修正規定--第2章心臟血管及腎臟藥物: 中央健康保險局; 2008。
14.行政院衛生署國民健康局。台灣地區高血壓、高血糖、高血脂盛行率調查報告 2003。
15.Grundy SM, Cleeman JI, Merz CN, et al. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation. 2004;110:227-239.
16.Chiu HC. Pharmacoeconomics (6): Evaluation of Lipid Lowering Drugs. Formosan J Med. 2004;8:130-134.
17.台灣藥物經濟評估方法學相關指南。1.0 ed; 2006。
18.Gold M, Siegel J, LB R, et al. Cost-Effectiveness in Health and Medicine. New York: Oxford University Press; 1996.
19.Drummond MF, Sculpher MJ, Torrance GW, et al. Methods for the economic evaluation of health care programmes. Third ed. Oxford: Oxford University Press; 2005.
20.Morrison A, Glassberg H. Determinants of the cost-effectiveness of statins. J Manag Care Pharm. 2003;9:544-551.
21.Guidelines for econommic evaluation of pharmaceuticals: Canadian. Ottawa: Canadian Agency for Drugs and Technologies in Health; 1997.
22.Mauskopf JA, Paul JE, Grant DM, et al. The role of cost-consequence analysis in healthcare decision-making. Pharmacoeconomics. 1998;13:277-288.
23.譚延輝。藥事經濟學入門: 九州圖書文物有限公司; 2000。
24.Wall DS, Abel SR. Therapeutic-interchange algorithm for multiple drug classes. Am J Health Syst Pharm. 1996;53:1295-1296.
25.李玟瑾。治療取代：評估降血脂類藥品statins之治療相等性以及選擇適當的statin藥品替代。國防醫學院藥學研究所藥事執業組碩士論文。2008。
26.Schachtner JM, Guharoy R, Medicis JJ, et al. Prevalence and cost savings of therapeutic interchange among U.S. hospitals. Am J Health Syst Pharm. 2002;59:529-533.
27.Tan-Torres Edejer T, Baltussen R, Adam T, et al. Making choices in health: WHO guide to cost-effectiveness analysis. Geneva: World Health Organization; 2003.
28.Murray CJ, Evans DB, Acharya A, et al. Development of WHO guidelines on generalized cost-effectiveness analysis. Health Econ. 2000;9:235-251.
29.Methods for Assessment of the Relation of Benefits to Costs in the German Statutory Health Care System. 1.1 ed: Institute for Quality and Efficiency in Health Care (IQWiG); 2008.
30.Benner JS, Smith TW, Klingman D, et al. Cost-effectiveness of rosuvastatin compared with other statins from a managed care perspective. Value Health. 2005;8:618-628.
31.Karlsson G, Johannesson M. The decision rules of cost-effectiveness analysis. Pharmacoeconomics. 1996;9:113-120.
32.Stamler J, Wentworth D, Neaton JD. Is relationship between serum cholesterol and risk of premature death from coronary heart disease continuous and graded? Findings in 356,222 primary screenees of the Multiple Risk Factor Intervention Trial (MRFIT). JAMA. 1986;256:2823-2828.
33.Law MR, Wald NJ, Thompson SG. By how much and how quickly does reduction in serum cholesterol concentration lower risk of ischaemic heart disease? BMJ. 1994;308:367-372.
34.Lacy CF, Armstrong LL, Goldman MP, et al. Drug information handbook : a comprehensive resource for all clinicians and healthcare professionals. 16th ed ed. Hudson, Ohio: Lexi-Comp; 2008-2009.
35.Fernandez ML, Webb D. The LDL to HDL cholesterol ratio as a valuable tool to evaluate coronary heart disease risk. J Am Coll Nutr. 2008;27:1-5.
36.Stampfer MJ, Sacks FM, Salvini S, et al. A prospective study of cholesterol, apolipoproteins, and the risk of myocardial infarction. N Engl J Med. 1991;325:373-381.
37.Gaziano JM, Hennekens CH, O'Donnell CJ, et al. Fasting triglycerides, high-density lipoprotein, and risk of myocardial infarction. Circulation. 1997;96:2520-2525.
38.馮淑芬。針對65歲以上族群以statin作預防性治療的成本效益分析。國立臺灣大學預防醫學研究所碩士論文。2003。
39.Costa-Scharplatz M, Ramanathan K, Frial T, et al. Cost-effectiveness analysis of rosuvastatin versus atorvastatin, simvastatin, and pravastatin from a Canadian health system perspective. Clin Ther. 2008;30:1345-1357.
40.Ohsfeldt RL, Gandhi SK, Fox KM, et al. Statin Cost-Effectiveness Comparisons Using Real-World Effectiveness Data: Formulary Implications. Value Health. 2008.
41.Pinto CG, Carrageta MO, Miguel LS. Cost-effectiveness of rosuvastatin in the prevention of ischemic heart disease in Portugal. Value Health. 2008;11:154-159.
42.Mevacor® 藥品仿單。
43.Pratin® 藥品仿單。
44.Zocor® 藥品仿單。
45.Lescol® 藥品仿單。
46.Lipitor® 藥品仿單。
47.Crestor® 藥品仿單。
48.Olsson AG, Istad H, Luurila O, et al. Effects of rosuvastatin and atorvastatin compared over 52 weeks of treatment in patients with hypercholesterolemia. Am Heart J. 2002;144:1044-1051.
49.Brown WV, Bays HE, Hassman DR, et al. Efficacy and safety of rosuvastatin compared with pravastatin and simvastatin in patients with hypercholesterolemia: a randomized, double-blind, 52-week trial. Am Heart J. 2002;144:1036-1043.
50.Shepherd J, Vidt DG, Miller E, et al. Safety of rosuvastatin: update on 16,876 rosuvastatin-treated patients in a multinational clinical trial program. Cardiology. 2007;107:433-443.
51.Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet. 1994;344:1383-1389.
52.Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. The Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group. N Engl J Med. 1998;339:1349-1357.
53.Helfand M, Carson S, Kelley C. Drug Class Review on HMG-CoA Reductase Inhibitors (Statins), Final Report. : Oregon Evidence-based Practice Center, Oregon Health & Science University; 2006.
54.全民健康保險研究資料庫。資料庫內容。http://w3.nhri.org.tw/nhird//date_cohort.htm#1.
55.中央健康保險局。用藥品項總檔。http://www.nhi.gov.tw/webdata/webdata.asp?menu=1&menu_id=498&webdata_id=873&WD_ID=. Accessed July 30, 2008.
56.中央健康保險局。全民健康保險醫療費用支付標準。http://www.nhi.gov.tw/webdata/webdata.asp?menu=1&menu_id=498&webdata_id=870&WD_ID=. Accessed September 1, 2008.
57.Sendi P, Al MJ. Revisiting the decision rule of cost-effectiveness analysis under certainty and uncertainty. Soc Sci Med. 2003;57:969-974.
58.Frolkis JP, Pearce GL, Nambi V, et al. Statins do not meet expectations for lowering low-density lipoprotein cholesterol levels when used in clinical practice. Am J Med. 2002;113:625-629.
59.Hudson M, Rahme E, Richard H, et al. Comparison of measures of medication persistency using a prescription drug database. Am Heart J. 2007;153:59-65.
60.Sikka R, Xia F, Aubert RE. Estimating medication persistency using administrative claims data. Am J Manag Care. 2005;11:449-457.
61.Davidson M, McKenney J, Stein E, et al. Comparison of one-year efficacy and safety of atorvastatin versus lovastatin in primary hypercholesterolemia. Atorvastatin Study Group I. Am J Cardiol. 1997;79:1475-1481.
62.Hunninghake D, Bakker-Arkema RG, Wigand JP, et al. Treating to meet NCEP-recommended LDL cholesterol concentrations with atorvastatin, fluvastatin, lovastatin, or simvastatin in patients with risk factors for coronary heart disease. J Fam Pract. 1998;47:349-356.
63.Brown AS, Bakker-Arkema RG, Yellen L, et al. Treating patients with documented atherosclerosis to National Cholesterol Education Program-recommended low-density-lipoprotein cholesterol goals with atorvastatin, fluvastatin, lovastatin and simvastatin. J Am Coll Cardiol. 1998;32:665-672.
64.Jones P, Kafonek S, Laurora I, et al. Comparative dose efficacy study of atorvastatin versus simvastatin, pravastatin, lovastatin, and fluvastatin in patients with hypercholesterolemia (the CURVES study). Am J Cardiol. 1998;81:582-587.
65.Gentile S, Turco S, Guarino G, et al. Comparative efficacy study of atorvastatin vs simvastatin, pravastatin, lovastatin and placebo in type 2 diabetic patients with hypercholesterolaemia. Diabetes Obes Metab. 2000;2:355-362.
66.Andrews TC, Ballantyne CM, Hsia JA, et al. Achieving and maintaining National Cholesterol Education Program low-density lipoprotein cholesterol goals with five statins. Am J Med. 2001;111:185-191.
67.Davidson MH, Palmisano J, Wilson H, et al. A multicenter, randomized, double-blind clinical trial comparing the low-density lipoprotein cholesterol-lowering ability of lovastatin 10, 20, and 40 mg/d with fluvastatin 20 and 40 mg/d. Clin Ther. 2003;25:2738-2753.
68.A multicenter comparative trial of lovastatin and pravastatin in the treatment of hypercholesterolemia. The Lovastatin Pravastatin Study Group. Am J Cardiol. 1993;71:810-815.
69.Effects of pravastatin in patients with serum total cholesterol levels from 5.2 to 7.8 mmol/liter (200 to 300 mg/dl) plus two additional atherosclerotic risk factors. The Pravastatin Multinational Study Group for Cardiac Risk Patients. Am J Cardiol. 1993;72:1031-1037.
70.Bertolini S, Bon GB, Campbell LM, et al. Efficacy and safety of atorvastatin compared to pravastatin in patients with hypercholesterolemia. Atherosclerosis. 1997;130:191-197.
71.Saklamaz A, Comlekci A, Temiz A, et al. The beneficial effects of lipid-lowering drugs beyond lipid-lowering effects: a comparative study with pravastatin, atorvastatin, and fenofibrate in patients with type IIa and type IIb hyperlipidemia. Metabolism. 2005;54:677-681.
72.Lefebvre P, Scheen A, Materne P, et al. Efficacy and tolerability of simvastatin and pravastatin in patients with primary hypercholesterolemia (multicountry comparative study). The European Study Group. Am J Cardiol. 1992;70:1281-1286.
73.Lambrecht LJ, Malini PL. Efficacy and tolerability of simvastatin 20 mg vs pravastatin 20 mg in patients with primary hypercholesterolemia. European Study Group. Acta Cardiol. 1993;48:541-554.
74.Stalenhoef AF, Lansberg PJ, Kroon AA, et al. Treatment of primary hypercholesterolaemia. Short-term efficacy and safety of increasing doses of simvastatin and pravastatin: a double-blind comparative study. J Intern Med. 1993;234:77-82.
75.Steinhagen-Thiessen E. Comparative efficacy and tolerability of 5 and 10 mg simvastatin and 10 mg pravastatin in moderate primary hypercholesterolemia. Simvastatin Pravastatin European Study Group. Cardiology. 1994;85:244-254.
76.Blasetto JW, Stein EA, Brown WV, et al. Efficacy of rosuvastatin compared with other statins at selected starting doses in hypercholesterolemic patients and in special population groups. Am J Cardiol. 2003;91:3C-10C; discussion 10C.
77.Shepherd J, Hunninghake DB, Barter P, et al. Guidelines for lowering lipids to reduce coronary artery disease risk: a comparison of rosuvastatin with atorvastatin, pravastatin, and simvastatin for achieving lipid-lowering goals. Am J Cardiol. 2003;91:11C-17C; discussion 17C-19C.
78.Jones PH, Davidson MH, Stein EA, et al. Comparison of the efficacy and safety of rosuvastatin versus atorvastatin, simvastatin, and pravastatin across doses (STELLAR* Trial). Am J Cardiol. 2003;92:152-160.
79.Effect of simvastatin on coronary atheroma: the Multicentre Anti-Atheroma Study (MAAS). Lancet. 1994;344:633-638.
80.Teo KK, Burton JR, Buller CE, et al. Long-term effects of cholesterol lowering and angiotensin-converting enzyme inhibition on coronary atherosclerosis: The Simvastatin/Enalapril Coronary Atherosclerosis Trial (SCAT). Circulation. 2000;102:1748-1754.
81.Dart A, Jerums G, Nicholson G, et al. A multicenter, double-blind, one-year study comparing safety and efficacy of atorvastatin versus simvastatin in patients with hypercholesterolemia. Am J Cardiol. 1997;80:39-44.
82.Crouse JR, 3rd, Frohlich J, Ose L, et al. Effects of high doses of simvastatin and atorvastatin on high-density lipoprotein cholesterol and apolipoprotein A-I. Am J Cardiol. 1999;83:1476-1477, A1477.
83.Marz W, Wollschlager H, Klein G, et al. Safety of low-density lipoprotein cholestrol reduction with atorvastatin versus simvastatin in a coronary heart disease population (the TARGET TANGIBLE trial). Am J Cardiol. 1999;84:7-13.
84.Insull W, Kafonek S, Goldner D, et al. Comparison of efficacy and safety of atorvastatin (10mg) with simvastatin (10mg) at six weeks. ASSET Investigators. Am J Cardiol. 2001;87:554-559.
85.Illingworth DR, Crouse JR, 3rd, Hunninghake DB, et al. A comparison of simvastatin and atorvastatin up to maximal recommended doses in a large multicenter randomized clinical trial. Curr Med Res Opin. 2001;17:43-50.
86.Branchi A, Fiorenza AM, Torri A, et al. Effects of low doses of simvastatin and atorvastatin on high-density lipoprotein cholesterol levels in patients with hypercholesterolemia. Clin Ther. 2001;23:851-857.
87.Karalis DG, Ross AM, Vacari RM, et al. Comparison of efficacy and safety of atorvastatin and simvastatin in patients with dyslipidemia with and without coronary heart disease. Am J Cardiol. 2002;89:667-671.
88.Kastelein JJ, Isaacsohn JL, Ose L, et al. Comparison of effects of simvastatin versus atorvastatin on high-density lipoprotein cholesterol and apolipoprotein A-I levels. Am J Cardiol. 2000;86:221-223.
89.Olsson AG, Eriksson M, Johnson O, et al. A 52-week, multicenter, randomized, parallel-group, double-blind, double-dummy study to assess the efficacy of atorvastatin and simvastatin in reaching low-density lipoprotein cholesterol and triglyceride targets: the treat-to-target (3T) study. Clin Ther. 2003;25:119-138.
90.Kadikoylu G, Yukselen V, Yavasoglu I, et al. Hemostatic effects of atorvastatin versus simvastatin. Ann Pharmacother. 2003;37:478-484.
91.Chan WB, Ko GT, Yeung VT, et al. A comparative study of atorvastatin and simvastatin as monotherapy for mixed hyperlipidaemia in Type 2 diabetic patients. Diabetes Res Clin Pract. 2004;66:97-99.
92.Schuster H, Barter PJ, Stender S, et al. Effects of switching statins on achievement of lipid goals: Measuring Effective Reductions in Cholesterol Using Rosuvastatin Therapy (MERCURY I) study. Am Heart J. 2004;147:705-713.
93.Liem AH, van Boven AJ, Veeger NJ, et al. Effect of fluvastatin on ischaemia following acute myocardial infarction: a randomized trial. Eur Heart J. 2002;23:1931-1937.
94.Herd JA, Ballantyne CM, Farmer JA, et al. Effects of fluvastatin on coronary atherosclerosis in patients with mild to moderate cholesterol elevations (Lipoprotein and Coronary Atherosclerosis Study [LCAS]). Am J Cardiol. 1997;80:278-286.
95.Serruys PW, Foley DP, Jackson G, et al. A randomized placebo-controlled trial of fluvastatin for prevention of restenosis after successful coronary balloon angioplasty; final results of the fluvastatin angiographic restenosis (FLARE) trial. Eur Heart J. 1999;20:58-69.
96.Serruys PW, de Feyter P, Macaya C, et al. Fluvastatin for prevention of cardiac events following successful first percutaneous coronary intervention: a randomized controlled trial. JAMA. 2002;287:3215-3222.
97.Jacotot B, Benghozi R, Pfister P, et al. Comparison of fluvastatin versus pravastatin treatment of primary hypercholesterolemia. French Fluvastatin Study Group. Am J Cardiol. 1995;76:54A-56A.
98.Riegger G, Abletshauser C, Ludwig M, et al. The effect of fluvastatin on cardiac events in patients with symptomatic coronary artery disease during one year of treatment. Atherosclerosis. 1999;144:263-270.
99.Sever PS, Dahlof B, Poulter NR, et al. Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial--Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial. Lancet. 2003;361:1149-1158.
100.Colhoun HM, Betteridge DJ, Durrington PN, et al. Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trial. Lancet. 2004;364:685-696.
101.Ferdinand KC, Clark LT, Watson KE, et al. Comparison of efficacy and safety of rosuvastatin versus atorvastatin in African-American patients in a six-week trial. Am J Cardiol. 2006;97:229-235.
102.Fonseca FA, Ruiz A, Cardona-Munoz EG, et al. The DISCOVERY PENTA study: a DIrect Statin COmparison of LDL-C Value--an Evaluation of Rosuvastatin therapY compared with atorvastatin. Curr Med Res Opin. 2005;21:1307-1315.
103.Jukema JW, Liem AH, Dunselman PH, et al. LDL-C/HDL-C ratio in subjects with cardiovascular disease and a low HDL-C: results of the RADAR (Rosuvastatin and Atorvastatin in different Dosages And Reverse cholesterol transport) study. Curr Med Res Opin. 2005;21:1865-1874.
104.Schneck DW, Knopp RH, Ballantyne CM, et al. Comparative effects of rosuvastatin and atorvastatin across their dose ranges in patients with hypercholesterolemia and without active arterial disease. Am J Cardiol. 2003;91:33-41.
105.Schwartz GG, Bolognese MA, Tremblay BP, et al. Efficacy and safety of rosuvastatin and atorvastatin in patients with hypercholesterolemia and a high risk of coronary heart disease: a randomized, controlled trial. Am Heart J. 2004;148:e4.
106.Stalenhoef AF, Ballantyne CM, Sarti C, et al. A comparative study with rosuvastatin in subjects with metabolic syndrome: results of the COMETS study. Eur Heart J. 2005;26:2664-2672.
107.Wolffenbuttel BH, Franken AA, Vincent HH. Cholesterol-lowering effects of rosuvastatin compared with atorvastatin in patients with type 2 diabetes -- CORALL study. J Intern Med. 2005;257:531-539.
108.Nissen SE, Tuzcu EM, Schoenhagen P, et al. Effect of intensive compared with moderate lipid-lowering therapy on progression of coronary atherosclerosis: a randomized controlled trial. JAMA. 2004;291:1071-1080.
109.Weir MR, Berger ML, Weeks ML, et al. Comparison of the effects on quality of life and of the efficacy and tolerability of lovastatin versus pravastatin. The Quality of Life Multicenter Group. Am J Cardiol. 1996;77:475-479.
110.Asselbergs FW, Diercks GF, Hillege HL, et al. Effects of fosinopril and pravastatin on cardiovascular events in subjects with microalbuminuria. Circulation. 2004;110:2809-2816.
111.Sacks FM, Pfeffer MA, Moye LA, et al. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events Trial investigators. N Engl J Med. 1996;335:1001-1009.
112.Cannon CP, Braunwald E, McCabe CH, et al. Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med. 2004;350:1495-1504.
113.Jukema JW, Bruschke AV, van Boven AJ, et al. Effects of lipid lowering by pravastatin on progression and regression of coronary artery disease in symptomatic men with normal to moderately elevated serum cholesterol levels. The Regression Growth Evaluation Statin Study (REGRESS). Circulation. 1995;91:2528-2540.
114.Pitt B, Mancini GB, Ellis SG, et al. Pravastatin limitation of atherosclerosis in the coronary arteries (PLAC I): reduction in atherosclerosis progression and clinical events. PLAC I investigation. J Am Coll Cardiol. 1995;26:1133-1139.
115.Bertrand ME, McFadden EP, Fruchart JC, et al. Effect of pravastatin on angiographic restenosis after coronary balloon angioplasty. The PREDICT Trial Investigators. Prevention of Restenosis by Elisor after Transluminal Coronary Angioplasty. J Am Coll Cardiol. 1997;30:863-869.
116.Shepherd J, Cobbe SM, Ford I, et al. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. West of Scotland Coronary Prevention Study Group. N Engl J Med. 1995;333:1301-1307.
117.Shepherd J, Blauw GJ, Murphy MB, et al. Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet. 2002;360:1623-1630.
118.Crouse JR, 3rd, Byington RP, Bond MG, et al. Pravastatin, Lipids, and Atherosclerosis in the Carotid Arteries (PLAC-II). Am J Cardiol. 1995;75:455-459.
119.Salonen R, Nyyssonen K, Porkkala E, et al. Kuopio Atherosclerosis Prevention Study (KAPS). A population-based primary preventive trial of the effect of LDL lowering on atherosclerotic progression in carotid and femoral arteries. Circulation. 1995;92:1758-1764.
120.李逸鴻。藥物經濟學在醫院藥品選擇的應用：以非典型抗精神病藥物為例。高雄醫學大學藥學研究所碩士在職專班碩士論文。2006。
121.林美汝。台灣地區血脂異常用藥之流行病學研究。高雄醫學大學藥學研究所碩士在職專班碩士論文。2005。
122.吳家雯。全民健康保險研究資料庫HMG-CoA Reductase Inhibitors處方型態及用藥安全性分析：自藥品交互作用觀點探討。臺灣大學臨床藥學研究所碩士論文。2005。
123.翁德昌。Statins類降血脂藥品處方型態分析及療效可替換性評估。國立成功大學臨床藥學研究所碩士論文。2007。
124.詹璧瑋。探討Statins類降血脂藥品在第二型糖尿病合併血脂異常患者之處方趨勢。高雄醫學大學藥學研究所碩士在職專班碩士論文。2008。
125.Chan P, Lee CB, Lin TS, et al. The effectiveness and safety of low dose pravastatin in elderly hypertensive hypercholesterolemic subjects on antihypertensive therapy. Am J Hypertens. 1995;8:1099-1104.
126.Hung YJ, Pei D, Wu DA, et al. Effects of lovastatin and gemfibrozil in subjects with high ratios of total cholesterol to high-density lipoprotein cholesterol. J Formos Med Assoc. 1999;98:104-110.
127.Lam HC, Chu CH, Wei MC, et al. The effects of different doses of atorvastatin on plasma endothelin-1 levels in type 2 diabetic patients with dyslipidemia. Exp Biol Med (Maywood). 2006;231:1010-1015.
128.Sheu WH, Jeng CY, Lee WJ, et al. Simvastatin treatment on postprandial hypertriglyceridemia in type 2 diabetes mellitus patients with combined hyperlipidemia. Metabolism. 2001;50:355-359.
129.Wang TD, Chen WJ, Lin JW, et al. Efficacy of fenofibrate and simvastatin on endothelial function and inflammatory markers in patients with combined hyperlipidemia: relations with baseline lipid profiles. Atherosclerosis. 2003;170:315-323.
130.Wu CC, Hsu TL, Chiang HT, et al. Efficacy and safety of slow-release fluvastatin 80 mg daily in Chinese patients with hypercholesterolemia. J Chin Med Assoc. 2005;68:353-359.
131.Yu WC, Chen CH, Tsao HM, et al. A randomized, double-blind comparison of cerivastatin and lovastatin for treatment of primary hypercholesterolemia. Chinese Medical Journal (Taipei). 2002;65:260-267.
132.Rasnake CM, Trumbo PR, Heinonen TM. Surrogate endpoints and emerging surrogate endpoints for risk reduction of cardiovascular disease. Nutr Rev. 2008;66:76-81.