血脂肪異常病人進行HMG-CoA還原?抑制劑相同療效藥品替代之評估

Therapeutic Interchange Evaluation of HMG-CoA Reductase Inhibitors in Patients with Dyslipidemia

林虹芸(Hong-Yun Lin)

指導教授 ： 廖嘉鴻 ； 簡淑真

臺北醫學大學/藥學院/藥學研究所/碩士(2006年)

摘要

研究目的: 研究醫院於94年6月6日起實行降血脂藥品3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor(簡稱HMG-CoA還原?抑制劑)之相同療效藥品替代。將原先的品項atorvastatin (Lipitor?)、simvastatin (Zocor?)、pravastatin (Mevalotin?)以及fluvastatin (Lescol?)以simvastatin (Zolotin?)以及atorvastatin (Lipitor?)進行替代。為了了解此藥品替代制度對於治療結果以及安全性的影響，故於療效方面評估替代前後血脂肪變化、達到美國國家膽固醇教育計畫第三版成人治療指引(National Cholesterol Education Program-Adult Treatment Panal III(簡稱 NCEP-ATP III)所制定低密度脂蛋白膽固醇控制目標的人數百分比；藥物安全性評估肝功能指數、肌酸激?、以及病歷上記載與藥品相關副作用。 研究方法: 本研究為非隨機分派(non-randomized)，開放性(open labled)，且自我比較(self-controlled)的研究。自2005年6月6日至2005年10月6日於研究醫院電腦系統篩選出使用simvastatin (Zolotin?)以及atorvastatin (Lipitor?)的病患。根據電腦內病患用藥紀錄以及生化檢查值紀錄進行研究的納入與排除。納入研究的病患於藥品替代後一個月至七個月內收集其血脂肪、肝功能指數、肌酸激?，並紀錄病歷中HMG-CoA還原?抑制劑所導致的副作用。療效性部分評估病患藥品替代前後總膽固醇(Total cholesterol，簡稱TC)、低密度脂蛋白膽固醇(Low-density lipoprotein cholesterol，簡稱LDL-C)、高密度脂蛋白膽固醇(High-density lipoprotein cholesterol，簡稱HDL-C)、三酸甘油酯(Triglyceride，簡稱TG)的變化以及達到NCEP-ATPIII中建議LDL控制目標值的人數百分比；副作用則評估肝功能指數Aspartate aminotransferase (簡稱AST)、Analine aminotransferase (簡稱ALT)的平均值以及肌酸激?(Creatine Kinase，簡稱CK)平均值於藥品替代前後的改變，藥品替代前後AST、ALT以及CK於分類範圍值內人數與百分比的變化，病歷上的HMG-CoA還原?抑制劑造成的副作用以及一級藥物交互作用的發生情形。 研究結果: statin替代制度後的四個月內，使用simvastatin (Zolotin?)或atorvastatin (Lipitor?)的病人分別有576與638人，根據納入與排除條件篩選後各有292以及97人進行評估。療效性部分無論替代為Zolotin?或Lipitor?皆使TC、LDL-C以及HDL-C皆呈現統計上顯著性的改善；使用Zolotin?的病人於藥品替代前後達到LDL目標值的人數百分比分別為8.6%與33.6%，Lipitor?則為5.8%與29.4%，兩組皆呈現顯著性上升(P<0.05)。副作用方面，雖然有1人AST，以及有4人ALT值上升大於三倍正常值，但並未出現肝臟副作用的臨床表徵，並且在換藥過後均採取停藥處置。藥品替代後僅有少數肌酸激?值大於正常值，肌酸激?值異常的病人均無出現肌肉副作用的臨床表徵。轉換為Zolotin?而產生肌肉副作用臨床表徵的八位病患中七人停止用藥。轉換為Lipitor?後影一人出現肌肉痙攣並且立即停藥。病歷上記載其他與HMG-CoA還原?抑制劑相關副作用的人數在換藥前後並無明顯的差異。而藥品替代前後均無出現和statin產生一級交互作用的情形 結論:以Zolotin?和Lipitor?進行相同療效藥品替代能使病人血脂肪值獲得改善，並且使達到LDL-C目標值的人數增加，所以整體來說，statin的藥品替代能達到較好的療效並且沒有嚴重不良反應的發生。

關鍵字

血脂肪異常 ； 相同療效藥品替代 ； HMG-CoA還原?抑制劑

並列摘要

Objective: Therapeutic interchange of HMG-CoA reductase inhibitors was implemented since June 6th, 2005. Atorvastatin (Lipitor?), simvastatin (Zocor?), pravastatin (Mevalotin?) and fluvastatin (Lescol?) were substituted with simvastatin (Zolotin?) and atorvastatin (Lipitor?). The purpose of this study was to evaluate the efficacy and safety of statin therapeutic interchange in patients with dyslipidemia. Method: This is a non-randomized, open-labeled and self-controlled study. Patients met the inclusion and exclusion criteria were eligible for the study and followed for seven months. Electronic prescription records and laboratory data of the subjects were collected one year before and seven months after interchange. The efficacy endpoints included changes in lipid profiles, including total cholesterol(TC), low-density lipoprotein cholesterol(LDL-C), high-density lipoprotein cholesterol(HDL-C) and triglyceride(TG), as well as the percentage of subjects attaining LDL-C goal according to National Cholesterol Education Program-Adult Treatment Panal III before and after interchange. Safety endpoints included aspartate aminotransferase (AST), alanine aminotransferase (ALT) and creatine kinase (CK), other statin-related adverse effects recorded in charts, and major drug interactions. Result: A total of 292 patients in the group of Zolotin? and 97 patients in the group of Lipitor? were eligible for the evaluation. TC, LDL-C and HDL-C values all improved after interchange. The percentage of patients achieving LDL-C goal significantly increased after converting to Zolotin? (8.3% VS 33.6%, p<0.05), while in Lipitor? users, the percentage increased from 5.8% to 29.4% (p<0.05). Although AST of one patient and ALT of four patients increased to three folds of upper limit of normal (ULN), none developed overt symptoms. Statin treatment were discontinued in these patients subsequently. During the 7 months after conversion, only a small number of people showed a slight increase in creatine kinase, but none developed clinical signs or symptoms. There were eight cases of muscle symptoms after converting to Zolotin?, seven of whom discontinued Zolotin? immediately. In the group of Lipitor? users, only one patient developed muscle cramping and discontinued treatment subsequently. There were no significant changes in any other adverse reactions. No major drug interaction was identified either before or after the interchange. Conclusion: Implementation of therapeutic interchange in statin improved the lipid profiles and increased the percentage of patients achieving LDL-C goal. Therefore, therapeutic interchange of statin may achieve better efficacy without causing severe adverse effects.

並列關鍵字

dyslipidemia ； therapeutic interchange ； HMG-CoA Reductase Inhibitors

參考文獻

3. 黃子芸."高血壓病人進行血管收縮素接受器阻斷劑相同療效藥品替代之評估" 民國94年

5. 行政院衛生署國民健康局http:// www.bhp.doh.gov.tw/(Accessed March 2006) 6 Wilson P, Abbott R, et al. "High density lipoprotein cholesterol andmortality. The Framingham Heart Study." Arteriosclerosis, Thrombosis, and Vascular Biology 1998;8(6): 737-7

7. Collaboration, A. P. C. S. "Cholesterol, coronary heart disease,and stroke in the Asia Pacific region." International Journal of Epidemiology 2003;32(4): 563-572.

8. Shepherd J. "Lipoprotein metabolism. " Drugs 1994;47:1-10

9. Knopp RH. "Drug Therapy: Drug Treatment of Lipid Disorders." New England Journal of Medicine 1999; 341: 498-511.