2022-台灣高血脂初級預防指引- 15. 藥物治療-statin

2025-12-09 11:08AM
2022台灣血脂治療指引(英文版)下面中文使用google自動翻譯

降低低密度脂蛋白膽固醇（LDL-C）水平的藥物治療，包括HMG-CoA還原酶抑制劑（他汀類藥物）、膽固醇吸收抑制劑（依折麥布）和前蛋白轉化酶枯草桿菌蛋白酶/kexin 9型（PCSK9）抑制劑，已證實對動脈粥狀硬化性心血管疾病（ASCVD）的二級預防有效。他汀類藥物是治療的基石，也被證實對第一級預防有效。依折麥布和PCSK9抑制劑作為他汀類藥物的輔助治療，在二級預防中能有效改善臨床結局，但這些藥物在第一級預防的應用尚未得到充分研究。他汀類藥物用於一級預防：他汀類藥物是ASCVD的第一線治療藥物，其在第一級預防中的益處已得到充分證實。一項納入 19 項隨機臨床試驗（n ≥ 71,344）的系統性回顧和統合分析評估了他汀類藥物與安慰劑或不使用他汀類藥物對心血管風險增加但既往無動脈粥樣硬化性心血管疾病 (ASCVD) 的成年人的影響，結果顯示他汀類藥物顯著降低了全因死亡率、心血管死亡率、心臟疾病的心臟死亡中因卒中的風險而降低了全因死亡率、心血管死亡率。 ⁹⁹ 在迄今為止規模最大的他汀類藥物一級預防干預試驗 JUPITOR 中，17,802 名低密度脂蛋白膽固醇 (LDL-C) < 130 mg/dL 但高敏 C 反應蛋白 (hs-CRP) 水平升高（≥ 2.0 mg/L）的健康受試者被隨機分配至每日服用 20 mg 水平升高（≥ 2.0 mg/L）的健康受試者被隨機分配至每日服用 20 mg 水平。 ¹⁰⁰ 經過 1.9 年的中位追蹤時間，他汀類藥物治療顯著降低了主要心血管事件、心血管死亡率和全因死亡率的發生率。 ¹⁰⁰ 在 HOPE3 試驗中，12,705 名無 ASCVD 但有中度風險的受試者被隨機分配至瑞舒伐他汀組。每日服用 10 毫克或安慰劑。兩組受試者的基線LDL-C水平均為127 mg/dL。 ¹⁰¹ 經過5.6年的隨訪，他汀類藥物治療組的心血管事件風險顯著低於安慰劑組。 ¹⁰¹ 在MEGA研究中，這是唯一一項針對亞洲人群的大型他汀類藥物一級預防試驗，7832名無冠心病或卒中病史的日本患者被隨機分配至單純飲食組或飲食聯合普伐他汀10-20 mg/天組。 ¹⁰² 平均追蹤5.3年後，他汀類藥物治療顯著降低了日本患者的冠心病事件風險。 ¹⁰² 他汀類藥物的強度分為三類：高強度他汀類藥物（劑量使LDL-C降低≥50%）、中等強度他汀類藥物（劑量使LDL-C降低30%-49%）和低強度他汀類藥物（劑量使LDL-C降低<30%）。 ¹⁰根據台灣的科學證據和基線低密度脂蛋白膽固醇（LDL-C）水平，建議先使用中等強度的他汀類藥物進行一級預防，如果未達到治療目標，則可逐漸增加劑量至高強度他汀類藥物。他汀類藥物的安全性已被廣泛評估。雖然偶有肌肉病變和肝功能異常的發生，但大多數患者對他汀類藥物治療的耐受性良好且安全。 ¹⁰³ 他汀類藥物相關的肌肉症狀是最常見的報告副作用，然而，嚴重他汀類藥物引起的肌肉損傷的風險…包括橫紋肌溶解症在內的不良反應發生率極低。 ¹⁰⁴ 請參閱2019年台灣脂質與動脈粥狀硬化學會關於他汀類藥物不耐受的專家共識聲明，以了解他汀類藥物相關肌肉和肝臟副作用的診斷和管理。 ¹⁰⁵ 他汀類藥物治療也與新發生糖尿病風險略有增加有關。一項納入91,140名參與者的13項他汀類藥物試驗的統合分析顯示，他汀類藥物治療與新發糖尿病風險增加9%相關。 ¹⁰⁶ 統合迴歸分析也表明，老年受試者服用他汀類藥物後新發糖尿病的風險更高，且與他汀類藥物的效力相關。 ¹⁰⁶


建議：對於一級預防，他汀類藥物是首選治療方案。可以先使用中等強度的他汀類藥物，如果未達到治療目標，再逐漸增加劑量至高強度他汀類藥物。 （COR I，LOE A）

Pharmacological therapy LDL-C lowering therapies with HMG CoA reductase inhibitors (statins), cholesterol absorption inhibitors (ezetimibe), and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, have demonstrated efficacy in secondary prevention of ASCVD. Statins, the cornerstone of therapy, are also found to be efficacious in primary prevention. Ezetimibe and PCSK9 inhibitors are effective in improving clinical outcomes as add-on drugs to statin therapy in secondary prevention, but these drugs have not been well investigated in patients for primary prevention. Statins for primary prevention Statins are the first-line therapy and the benefit of statins for primary prevention of ASCVD is well established. In a systematic review and meta-analysis of 19 randomized clinical trials (n Z 71,344) that evaluated the effect of statins versus placebo or no statin in adults at increased CV risk but without prior ASCVD, statins significantly reduced risk of all-cause mortality, CV mortality, stroke, MI, and composite CV outcomes.99 In JUPITOR trial, the largest statin intervention trial for primary prevention, 17,802 apparently healthy persons with LDL-C <130 mg/dL but with elevated high-sensitivity C-reactive protein levels (
2.0 mg/L) were randomly assigned to rosuvastatin 20 mg daily or placebo.100 After a median follow-up of 1.9 years, statin therapy significantly reduced the incidence of major CV events, CV mortality and all-cause mortality.100 In HOPE3 trial, 12,705 participants without ASCVD but at intermediate risk were randomly assigned to rosuvastatin 10 mg daily or placebo. The LDL-C levels at baseline were 127 mg/ dL in both groups.101 After a period of 5.6 years, treatment with statin resulted in a significantly lower risk of CV events than placebo.101 In MEGA study, the only large statin trial in Asian population for primary prevention, 7832 Japanese patients without history of CAD or stroke were randomly assigned to the diet only group or diet plus pravastatin 10e20 mg/day group.102 After a mean follow-up of 5.3 years, treatment with statin significantly reduced the risk of CAD events in Japanese patients.102 The intensity of statin is divided into 3 categories: highintensity statin (the dose reduces LDL-C by greater than or equal to 50%), moderate-intensity statin (the dose reduces LDL-C by 30%e49%), and low-intensity statin (the dose reduces LDL-C by <30%).10 Based on the scientific evidence and baseline LDL-C levels in Taiwan, it is reasonable to initiate moderate-intensity statin first for primary prevention and titrate to high-intensity statin if the treatment goal is not reached. The safety of statins has been extensively evaluated. Although myopathy and abnormal liver function are encountered occasionally, statin therapy is well tolerated and safe for most patients.103 Statinassociated muscle symptoms are the most common reported side effects, however, the risk of severe statininduced muscle injury, including rhabdomyolysis, is very low.104 Please refer to the 2019 Taiwan Society of Lipids and Atherosclerosis Expert Consensus Statement on Statin Intolerance for the diagnosis and management of statinrelated muscle and hepatic side effects.105 Statin therapy is also associated with a slightly increased risk of new-onset diabetes. In a meta-analysis including 13 statin trials with 91,140 participants, statin therapy was associated with a 9% increased risk for incident diabetes.106 The meta-regression analysis also indicated that the risk of new-onset diabetes with statins was higher in older subjects and associated with the statin’s potency.106


Recommendation For primary prevention, statins are the first-line therapy. It is reasonable to initiate moderate-intensity statin first and titrate to high-intensity statin if the treatment goal is not reached. (COR I, LOE A).