某教學醫院高血脂初級與次級預防患者Statin類藥品使用回溯性分析研究

A Retrospective Study of Statin Use for Primary and Secondary Prevention in a Teaching Hospital

張秀玲(Hsiu-Ling Chang)

指導教授 ： 詹道明

共同指導教授 ： 吳造中

高雄醫學大學/藥學院/藥學研究所碩士在職專班/碩士(2006年)

摘要

前言
心血管疾病(Cardiovascular disease, CVD) 及其相關冠狀動脈心臟疾病(Coronary heart disease, CHD)是美國及其他國家最常見的疾病，也是導致病人死亡率的主因。 ㄧ般而言，低密度脂蛋白膽固醇(Low-density lipoprotein cholesterol, LDL-C)濃度過高可能增加冠狀動脈心臟疾病、心肌梗塞及中風發生的危險性。近年來，有許多有效控制組臨床試驗研究證實HMG-CoA還原抑制劑(Hydroxy-methylglutaryl coenzyme A reductase inhibitors, 簡稱statin)積極治療能有效降低嚴重心血管事件的發生。因此，目前臨床治療高血脂目標為更嚴格控制血中LDL-C達到其治療目標，尤其是在高危險性次級預防的病患。
研究方法
本研究為回溯性觀察研究電腦隨機篩選92年9月至93年12月間，某教學醫學曾經服用statin類藥物作為次級預防的病患，評
估總膽固醇(Total choleserol, TC) 和LDL-C 値降低程度，及在不同危險分級之降血脂達成率。降血脂達成率是依據中央健保局於91年9月1日公佈降血脂藥物給付規定(http://www.nhi.gov.tw)。安全性評估指標主要是依據病患服藥後的生化檢驗值ALT (Alanine aminotransferase)及肌酸激酶(Creatine kinase, CK) 判斷不良反應的發生。
結果
本研究收集開始為單獨服用statin相同劑量治療的者，總共收納961位研究個案。研究個案平均年齡為57.7±12.6歲 (男性佔42.5% ，女性 佔57.5%)，依據中央健保局公告將研究對象依此標準區分為Group 1為CVD或糖尿病有388人，佔40.4%，比其他兩組更具顯著意義(p<0.001)；Group 2為非CVD 和糖尿病且危險因子數目≧2有297人，佔30.9%；Group 3為非CVD 和糖尿病且危險因子數目＜2有276人，佔28.7%。評估本研究個案達到中央健保局設定的治療目標，只有64.9% LDL-C達成率和40.0%的 TC達成率。在危險分級group 1, 2, 3的LDL-C和TC的下降達成率分別為34.5%, 13.5%; 80.8%, 39.2 %; 92.7%, 76.6 %。在研究個案最常使用的各statin 每日劑量為atorvastatin 10 mg (93.4 %)， fluvastatin 40 mg (96.7%)， lovastatin 20 mg (96.7%)， pravastatin 10 mg (84.1%)，及simvastatin 20 mg (84.3%)。血液檢驗中個案服用各statin後產生aminotransferase值大於三倍正常值的上升佔0.1%。研究期間並未發現有CK值大於10倍正常值的上升或橫紋肌溶解症。
結論
本研究中有大部分高血脂病患並未達到中央健保局設定LDL-C 的目標達成率。研究結果顯示血脂異常的病患應積極治療，才能達到建議的血脂達成值。

關鍵字

初級預防 ； 次級預防 ； Statin ； LDL-C達成率 ； 橫紋肌溶解症

並列摘要

Introduction
Cardiovascular disease (CVD) and its subset coronary heart disease (CHD) are leading causes of morbidity and mortality in the United States and worldwide. In general, higher levels of low-density lipoprotein cholesterol (LDL-C) are associated with an increased risk of coronary heart disease, myocardial infarction, and stroke. Recently, several active control trials have reported that more intensive HMG-CoA reductase inhibitor (statin) therapy results in a greater reduction in adverse cardiovascular outcomes compared with more moderate treatment. Accordingly, guidelines now recommend achieving more aggressive LDL-C target levels in certain very high-risk secondary prevention patients.
Methods
This is a retrospective chart review study to evaluate the percentage of achieving target total choleserol (TC) and/or LDL-C levels and the reduction rate of blood lipid with various kind and dosage of statin during the period from September 1, 2003 to December 31, 2004 in the National Taiwan University Hospital .The target TC and/or LDL-C levels defined the guideline recommended by Bureau of National Health Insurance (BNHI), Taiwan on September 1, 2002. (http://www.nhi.gov.tw/). Safety end points included an analysis of preconversion and postconversion alanine aminotransferase (ALT) tests and creatine kinase (CK) values.
Results
A total of 961 converted patients met criteria who continuously undertaking a specific type and dosage of statin for inclusion in the analysis. The average age 57.7±12.6 years (42.5% male, 57.5% female). The patients were divided into three groups: 40.4% (p<0.001) had established CVD or diabetes mellitus (group 1), 30.9% had 2 or more risk factors but no evidence of CVD or diabetes mellitus (group 2), 28.7% had fewer than 2 risk factor and no evidence of CVD or diabetes mellitus (group 3). Overall, only 64.9% and 40.0% of patients usual dose achieved BNHI-specified LDL-C and TC target levels. The LDL-C and TC reduction success rate in 1, 2, 3 group was 34.5%, 13.5%; 80.8%, 39.2 %; 92.7%, 76.6 %, respectively. The appropriate usual dose of each statin was 10 mg for atorvastatin (93.4%), 40 mg for fluvastatin (96.7%), 20 mg for lovastatin (96.7%), 10 mg for pravastatin (84.1%), and 20 mg for simvastatin (84.3%). The percentage of patients with serum ALT greater than 3 times the upper limit of normal (ULN) after statin treatment was 0.1%. No cases of creatine kinase elevations greater then 10 times the ULN or rhabdomyolysis were reported in any statin.
Conclusions
Large proportions of dyslipidemic patients receiving lipid-lowering therapy could not achieve the BNHI LDL-C target levels. These findings indicate that more aggressive treatment of dyslipidemia is needed to achieve the goals established by BNHI guideline.

並列關鍵字

Primary Prevention ； Secondary Prevention ； Statin ； LDL-C success rate ； Rhabdomyolysis

參考文獻

Abookire SA, Karson AS, Fiskio J, et al. Use and monitor of “statin” lipid-lowering drugs compared with guidelines. Arch Intern Med (2001) 161: 53-58.

Ahmed SM, Clasen ME, Donnelly JF. Management of dyslipidemia in adults. Am Fam Physician (1998) 57(9): 2207-2226.

Amarenco P, Bst JL, Lavalle´e P, et al. Statins in stroke prevention and carotid atherosclerosis systematic review and up-to-date meta-analysis. Stroke (2004) 35: 2902-2909.

Ballantyne CM, Arroll B, Shepherd J. Lipids and CVD management: towards a global consensus. Eur Heart J (2005) 26: 2224-2231.

Ballantyne CM, Corsini A, Davidson MH, et al. Risk for myopathy with statin therapy in high-risk patients. Arch Intern Med (2003) 163: 553-564.