目的：
由於冠狀動脈疾病為全球發病率及死亡率占很重要的原因，而高血脂症為好發心血管疾病之高危險群，病患在服用statin類高血脂藥物之順從與否對於病患導致冠狀動脈心臟病（CHD）占很重要原因，因此本研究欲探討病患服用statins類藥物之順從性高低，進而導致發生冠狀動脈疾病（CHD）之情形，並分析其醫療花費之相關性。

方法：
本研究採用全國代表性資料之全民健康保險研究資料庫，分析2001年至2007年之門診（CD及OO）、住院（DD）、健保藥局處方醫令明細檔（GD及GO）及醫事機構基本資料檔（HOSB）。將2002年至2005年每年篩選出第一次服用statin類藥物並且無任何冠狀動脈疾病病史，並追蹤其三年之用藥紀錄以計算服藥順從性（MPR）直到病患因發生冠心症而導致入院或觀察期結束為止。本研究使用卡方檢定以及t檢定分析各變項在順從性高低分組中是否有差異；使用邏輯式迴歸及線性迴歸分析自變項在控制其他變項後與住院情形及醫療資源花費之關係。

結果：
本研究最後納入樣本19371人，其中高服藥順從性（MPR≧80％）有7909人，低服藥順從性（MPR＜80％）則有11462人。在追蹤三年後探討其服藥順從性、發生冠心症（CHD）住院及醫療資源花費情形，發現男性、高齡、疾病嚴重度（CCI）等於1、醫學中心等變項在順從性呈現較高趨勢；順從性較高之病患其發生住院之風險較低，而男性、年紀較高、疾病嚴重度較高、教學醫院、越鄉村之地區發生住院之風險呈現較高之趨勢；在住院花費方面，順從性較低之病患、男性、高齡、疾病嚴重度高其住院花費較高，而在醫學中心、教學醫院、城市地區及私立醫院就醫之病患亦呈現較高住院費用。

結論：
服藥順從性是主要影響疾病預防效果的關鍵。在本研究發現到，藥品順從性越高，其住院發生率就越低，突顯出藥品持有率對於預防心血管疾病的重要性，並且良好的藥物順從性亦能有效降低住院花費。

Objective：
The purpose of this study is to explore the relationship of patients’ medication adherence with the statins therapy and inpatient visit the in Taiwan.

Methods：
A corhort study was implemented to use the National Health Insurance Research Database（NHIRD）between January 2001 and December 2007, to analysis the patient who had taken the medicine of statins at the first time and never had diagnosis of coronary heart disease（CHD）. The patient were followed until occurred first inpatient visit with coronary heart disease or end of study period（Dec. 31 2007）. The medication adherence was calculated as medication possession ratio（MPR）which was sum of days of supply of the statins medications divided by follow-up duration.

Result：
In the analyzed of 19371 patients who use statins therapy, 11642 patients（59.17%）had high medication adherence（MPR≧80％）and the rest patients（40.83%）had been included in low medication adherence（MPR＜80％）. There were significantly higher adherence for patients were male, elderly, CCI=1, in medical center and in rural area. The hospitalized risk increased with MPR<80 %, male, elderly, and more comorbidities. The hospitalization costs showed comorbidities with MPR<80 %, male, elderly, more comorbidities, patient in medical center, teaching-hoapital and suburban.

Conclution：
Lipid-lowering therapy, statins medication is well known to reduce cardiovascular risk across a wide range of patients. It is very important to follow-up and compliance with statins therapy. This study finded that good adherence to statin treatment was associated with lower risk of occurred CHD.

論文審定書 i
誌謝 ii
中文摘要 iii
ABSTRACT iv
目錄 v
圖 次 vii
表 次 viii
第一章 緒論 1
第一節 研究背景及動機 1
第二節 研究目的 2
第二章 文獻查證 3
第一節 心血管疾病之流行病學 3
第二節 STATINS 類藥品之定義與使用規範 10
第三節 高血脂與心血管疾病之相關研究 13
第四節 藥品順從性之定義 14
第五節 藥品順從性與冠狀動脈心臟病之相關性探討 18
第六節 相關醫療資源利用之情形 24
第三章 研究方法 25
第一節 研究假設與架構 25
第二節 研究對象與研究抽樣流程 28
第三節 研究變項操作型定義 32
第四節 研究分析工具及方法 38
第四章 研究分析與結果 39
第一節 描述性統計分析 39
第二節 推論性統計分析 45
第五章 討論 56
第一節 人口學變項及醫事機構特性 56
第二節 發生住院風險 57
第三節 發生急診風險 58
第四節 住院花費使用情形 58
第六章 結論與建議 59
第一節 結論 59
第二節 建議 59
第三節 研究限制 60
第四節 研究貢獻 60
參考文獻 62
中文文獻 62
英文文獻 63

中文文獻
丁予安, 行政院衛生署國民健康局, & 中華民國血脂及動脈硬化學會. (2003). 高血脂防治手冊: 國人血脂異常診療及預防指引: 行政院衛生署國民健康局.
全民健康保險局. (2010). 98年單方藥品申報金額排行. 全民健康保險申報資料倉儲系統門住診及交付機構醫令檔.
行政院衛生署. (2012). 死因統計統計表, 100 年度主要死因死亡統計. 取自http://www.mohw.gov.tw/cht/DOS/Statistic.aspx?f_list_no=312&fod_list_no=2747
行政院衛生署國民健康局.(2005). 高血脂紅色通緝令.取自 http://www.bhp.doh.gov.tw/BHPNet/Portal/file/ThemeULFile/20070820300000004/0001.pdf.
林毓瑩. (2004). 各種 Statin 降血脂藥的比較. 台北醫學大學附設醫院藥劑部用藥安全電子報, 5.
劉秉彥, & 陳志鴻. (2002). 冠狀動脈疾病. 科學發展, 352, 48-53.


英文文獻
Assmann, G., & Schulte, H. (1992). Relation of high-density lipoprotein cholesterol and triglycerides to incidence of atherosclerotic coronary artery disease (the PROCAM experience). The American Journal of Cardiology, 70(7), 733-737.
Avorn, J., Monette, J., Lacour, A., Bohn, R. L., Monane, M., Mogun, H., & LeLorier, J. (1998). Persistence of use of lipid-lowering medications: a cross-national study. JAMA, 279(18), 1458-1462.
Baigent, C., Keech, A., Kearney, P. M., Blackwell, L., Buck, G., Pollicino, C., . . . Cholesterol Treatment Trialists, C. (2005). Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet, 366(9493), 1267-1278. doi: 10.1016/S0140-6736(05)67394-1
Benner, J. S., Glynn, R. J., Mogun, H., Neumann, P. J., Weinstein, M. C., & Avorn, J. (2002). Long-term persistence in use of statin therapy in elderly patients. JAMA, 288(4), 455-461.
Chiang, C. W., Chiu, H. F., Chen, C. Y., Wu, H. L., & Yang, C. Y. (2008). Trends in the use of lipid‐lowering drugs by outpatients with diabetes in Taiwan, 1997–2003. Pharmacoepidemiol Drug Saf, 17(1), 62-69.
Fonarow, G. C., French, W. J., Parsons, L. S., Sun, H., & Malmgren, J. A. (2001). Use of lipid-lowering medications at discharge in patients with acute myocardial infarction data from the National Registry of Myocardial Infarction 3. Circulation, 103(1), 38-44.
Foody, J. M. (2006). Adherence To Lipid Lowering - Growing Clinical Challenge. US Cardiology Disease, 3(2), 7.
Gandhi, S. K., Jensen, M. M., Fox, K. M., Smolen, L., Olsson, A. G., & Paulsson, T. (2012). Cost-effectiveness of rosuvastatin in comparison with generic atorvastatin and simvastatin in a Swedish population at high risk of cardiovascular events. ClinicoEconomics and Outcomes Research: CEOR, 4, 1.
Grant, R. W., Pirraglia, P. A., Meigs, J. B., & Singer, D. E. (2004). Trends in complexity of diabetes care in the United States from 1991 to 2000. Archives of Internal Medicine, 164(10), 1134.
Group, M. R. F. I. T. R. (1982). Multiple risk factor intervention trial. JAMA: the journal of the American Medical Association, 248(12), 1465-1477.
Heiss, G., Tamir, I., Davis, C. E., Tyroler, H. A., Rifkind, B. M., Schonfeld, G., . . . Frantz Jr, I. D. (1980). Lipoproteins: cholesterol distributions in selected North American populations: the lipid research clinics program prevalence study. Circulation, 61(2), 302-315.
Hunninghake, D. B., Knopp, R. H., Schonfeld, G., Goldberg, A. C., Brown, W. V., Schaefer, E. J., . . . et al. (1990). Efficacy and safety of pravastatin in patients with primary hypercholesterolemia. I. A dose-response study. Atherosclerosis, 85(1), 81-89.
Huser, M. A., Evans, T. S., & Berger, V. (2005). Medication adherence trends with statins. Advances in Therapy, 22(2), 163-171.
Jackevicius, C. A., Mamdani, M., & Tu, J. V. (2002). Adherence with statin therapy in elderly patients with and without acute coronary syndromes. JAMA, 288(4), 462-467.
Kim, H.-S., Wu, Y., Lin, S.-J., Deerochanawong, C., Zambahari, R., Zhao, L., . . . Yan, P. (2008). Current status of cholesterol goal attainment after statin therapy among patients with hypercholesterolemia in Asian countries and region: the Return on Expenditure Achieved for Lipid Therapy in Asia (REALITY-Asia) study. Current Medical Research and Opinion®, 24(7), 1951-1963.
Lage, M. J., & Hassan, M. K. (2009). The relationship between antipsychotic medication adherence and patient outcomes among individuals diagnosed with bipolar disorder: a retrospective study. Ann Gen Psychiatry, 8, 7. doi: 10.1186/1744-859X-8-7
Lee, K. (2010). Cardiovascular risk prevalence, awareness, treatment, and control from 1998 to 2007 in Koreans. Asia Pacific Journal of Clinical Nutrition, 19(2), 261.
Mansur, A. P., Mattar, A. P., Tsubo, C. E., Simão, D. T., Yoshi, F. R., & Daci, K. (2001). Prescription and adherence to statins of patients with coronary artery disease and hypercholesterolemia. Arquivos Brasileiros de Cardiologia, 76(2), 115-118.
Maron, D. J., Fazio, S., & Linton, M. F. (2000). Current perspectives on statins. Circulation, 101(2), 207-213.
McCombs, J. S., Nichol, M. B., Newman, C. M., & Sclar, D. A. (1994). The costs of interrupting antihypertensive drug therapy in a Medicaid population. Med Care, 32(3), 214-226.
Miller, M., Byington, R., Hunninghake, D., Pitt, B., & Furberg, C. D. (2000). Sex bias and underutilization of lipid-lowering therapy in patients with coronary artery disease at academic medical centers in the United States and Canada. Archives of Internal Medicine, 160(3), 343-347.
Mokdad, A. H., Marks, J. S., Stroup, D. F., & Gerberding, J. L. (2004). Actual causes of death in the United States, 2000. JAMA, 291(10), 1238-1245.
Nau, D. P., & Director, C. S. (2012). Proportion of days covered (PDC) as a preferred method of measuring medication adherence: Pharmacy Quality Alliance.
Pan, W.-H., & Chiang, B. N. (1995). Plasma lipid profiles and epidemiology of atherosclerotic diseases in Taiwan—a unique experience. Atherosclerosis, 118(2), 285-295.
Parris, E. S., Lawrence, D. B., Mohn, L. A., & Long, L. B. (2005). Adherence to Statin Therapy and LDL Cholesterol Goal Attainment by Patients With Diabetes and Dyslipidemia. Diabetes Care, 28(3), 595-599. doi: 10.2337/diacare.28.3.595
Posey, L. M. (2005). Pharmacotherapy: A Pathophysio/ogic Approach (Vol. 21): New York, NY: McGraw-Hill.
Rasmussen, J. N., Chong, A., & Alter, D. A. (2007). Relationship between adherence to evidence-based pharmacotherapy and long-term mortality after acute myocardial infarction. JAMA, 297(2), 177-186. doi: 10.1001/jama.297.2.177
Roberts, A. W., Crisp, G. D., Esserman, D. A., Roth, M. T., Weinberger, M., & Farley, J. F. (2014). Patterns of medication adherence and health care utilization among patients with chronic disease who were enrolled in a pharmacy assistance program. North Carolina Medical Journal, 75(5), 310.
Spence, M. M., Makarem, A. F., Reyes, S. L., Rosa, L. L., Nguyen, C., Oyekan, E. A., & Kiyohara, A. T. (2014). Evaluation of an Outpatient Pharmacy Clinical Services Program on Adherence and Clinical Outcomes Among Patients with Diabetes and/or Coronary Artery Disease. Journal of Managed Care Pharmacy: JMCP, 20(10), 1036-1045.
Tang, C. H., Hsieh, M. H., Hung, S. T., Lee, I. H., Lin, Y. J., & Yang, Y. K. (2010). One-year post-hospital medical costs and relapse rates of bipolar disorder patients in Taiwan: a population-based study. Bipolar Disord, 12(8), 859-865. doi: 10.1111/j.1399-5618.2010.00878.x
Wallach-Kildemoes, H., Andersen, M., Diderichsen, F., & Lange, T. (2013). Adherence to preventive statin therapy according to socioeconomic position. European Journal of Clinical Pharmacology, 69(8), 1553-1563.
Wei, L., Wang, J., Thompson, P., Wong, S., Struthers, A. D., & MacDonald, T. M. (2002). Adherence to statin treatment and readmission of patients after myocardial infarction: a six year follow up study. Heart, 88(3), 229-233. doi: DOI 10.1136/heart.88.3.229
Wilson, J., Axelsen, K., & Tang, S. (2005). Medicaid prescription drug access restrictions: exploring the effect on patient persistence with hypertension medications. Am J Manag Care, 11(Espec No).
Wu, P. H., Yang, C. Y., Yao, Z. L., Lin, W. Z., Wu, L. W., & Chang, C. C. (2010). Relationship of blood pressure control and hospitalization risk to medication adherence among patients with hypertension in Taiwan. Am J Hypertens, 23(2), 155-160. doi: 10.1038/ajh.2009.210
Yan, P. (2008). Cardiovascular Disease Risk Management in Diabetes-The Implications of the REALITY Asia Study. ASIA-PACIFIC CARDIOLOGY.