已有許多國外臨床研究顯示simvastatin對高血脂症具有良好的治療效果與安全性，但都是針對西方人種，少有東方人種或國內的研究結果。由於本國的健保制度規定處方simvastatin高血脂藥物從最低有效劑量(20mg)開始使用，而且以3個月為一觀察評估期，視需要再調整劑量。因此，基於國內也少有投與simvastatin於高血脂病患的臨床研究，以及符合本國健保局的規定與藥物經濟性之考量，設計此一研究，藉由投與最低有效劑量的simvastatin予高血脂病患，來評估是否最低有效劑量的simvastatin就具有療效性與服用的安全性。本試驗為隨機的設計，先篩選出65位原發性高血脂症病患，先進入4週的飲食控制期，然後僅有49位參與實驗者則開始投與每天20mg simvastatin，連續治療12週後，觀察總膽固醇、三酸甘油脂、低密度脂蛋白、高密度脂蛋白等數值變化，與其他可供評估安全性的各項血液生化數值之變化，並記錄受試者回診時的主訴不良反應。總共39位病患完成整個療程並符合計劃書的實驗設計之進行。療效方面，服藥12週後，總膽固醇平均值(196.4±41.8 mg/dL)降低22.5％(p<0.001)，三酸甘油脂平均值(134.8±88.3mg/dL)降低31.8％(p=0.006)，低密度脂蛋白平均值(109.3±34.5 mg/dL)降低29.8％(p<0.001);以上降低的程度，皆達統計上有意義的差異。鹼性磷酸&#37238;與鈣質等數值在服藥12週後皆無明顯地改變。男性服藥後的TG平均值下降並不明顯，但女性服藥後的TG平均值下降卻非常顯著，服用simvastatin 12週後對TG值的影響有性別上的差異性。吸煙者服藥後的TG平均值下降並不明顯，但未吸煙者服藥後的TG平均值卻有顯著下降效果，服用simvastatin 12週後對TG值的影響有吸煙與否的差異性。安全性方面，49位參與實驗者中有7位(14.3%)，其中3位(6.1%)中止試驗，曾有肌肉酸痛發生; 有17位(34.7%)發生短暫且輕微的AST與ALT等肝功能指數上升，但無發生明顯肝臟受損的病例。結論是，simvstatin有降低血脂肪的療效，尤其是降低總膽固醇和低密度脂蛋白的效果顯著，而且耐受性佳。

Background. The published reports of the effectiveness of simvastatin in treatment of hypercholesterolemia were mostly conducted in western populations, and only few studies in Asian or domestic populations have ever been reported. By regulations from Bureau of National Health Insurance, the effective dosage of lipid lowering agents should be started from lower dose, such as 20 mg of simvastatin per day. Whether this dosage of simvastatin is effective for treatment of patients with hypercholesterolemia and the efficacy and safety of such dosage are the objects of this study.
Materials and Methods. After the approval of IRB in a medical center located at north Taiwan, a randomized 12-week study was conducted to evaluate the efficacy and safety of 20mg/day simvastatin treatment on hypercholesterolemia. By randomization 65 patients, followed up at cardiovascular outpatient department under the diagnosis of primary hypercholesterolemia, were enrolled into a 4-week washout period, and finally 49 intent-to-treat patients entered a 12-week treatment with 20mg simvastatin per day, given through oral routine in the evening. Demographic and laboratory data were obtained before and after treatment. The primary efficacy measure was the changes from baseline in lipid parameters. Tolerability was assessed in terms of the overall incidence of adverse experiences and the most commonly reported adverse experiences.
Results. The per-protocol analyses included 39 hypercholesterolemic patients whom completed 12 weeks of therapy. Total cholesterol and LDL cholesterol at the end of the study period showed significant reductions by 22.5％ (p<0.001) and 29.8％(p<0.001), respectively. Triglyceride also showed a significant reduction by 31.8% (p=0.006), whereas total alkaline phosphatase and calcium showed a weak and insignificant change over the study period. The female group had significantly greater reduction in triglyceride than that in the male group, and the non-smoking group also had significantly greater reduction in triglyceride than that in smoking group after 12-week treatment. There were 17 studied cases (34.7%) had minor transient but clinical insignificant increases in serum aspartate aminotransferase and alanine aminotransferase, and 7 cases (14.3%) experienced symptom of painful muscle, of whom 3 cases (6.1%) dropped out this study.
Conclusion. Our results, although obtained from a small scale of hypercholesterolemic patients, suggest a probable positive efficacy and good tolerability with only few minor side effects of simvastatin on blood lipids.

中文摘要……………………………………………………………………..I
英文摘要…………………………………………………………………….III
英文縮寫表………………………………………………………………….IV
論文內文……………………………………………………………………..1
一.背景介紹與目的………………………………………………….......1
二.研究方法與材料…………………………………………………….20
三.實驗結果…………………………………………………………….28
四. 討論………………………………………………………………...34
參考文獻……………………………………………………………………43
表……………………………………………………………………………54
圖……………………………………………………………………………65

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