Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in High-Risk Adults: The Current Guidelines and New Drugs

治療膽固醇與降低動脈粥樣硬化心血管風險：簡介目前的治療指引與新穎藥物

林肇鋒(Chao-Feng Lin) ； 簡世杰(Shih-Chieh Chien) ； 林岳鴻(Yueh-Hung Lin) ； 吳懿哲(Yih-Jer Wu) ； 蘇正煌(Cheng-Huang Su) ； 葉宏一(Hung-I Yeh)

《內科學誌》 28卷4期 (2017/08) Pp. 223-231

https://doi.org/10.6314/JIMT.2017.28(4).05

摘要

Statins have been the main treatment for patients with dyslipidemia and for prevention of clinical atherosclerotic cardiovascular disease (ASCVD). According to the 2013 American College of Cardiology / American Heart Association (ACC/AHA) lipid guideline, four statin benefit groups were issued, including patients with clinical ASCVD, low-density lipoprotein cholesterol (LDL-C) ＞190 mg/dL, diabetes mellitus (DM), or with 10-year ASCVD risk of ＞7.5%. Although the ACC/AHA guideline suggested the intensity of statin treatment for patients with different risk categories, it did not recommend the specific target levels of LDL-C. The 2016 European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS) guideline suggested the SCORE system for risk assessment. For very high-risk, high-risk, and moderate-risk patients, the treatment goals of LDL-C were ＜70 mg/dL, ＜100 mg/dL, and ＜115 mg/dL, respectively. The 2017 Taiwan lipid guidelines clearly defined the high-risk patients and the treatment goals of LDL-C. For patients with peripheral arterial disease (PAD), cerebrovascular disease, DM, and familial hypercholesterolemia (FH), the LDL-C ＜100 mg/dL is suggested, whereas LDL-C ＜70 mg/dL is suggested for patients with acute coronary syndrome (ACS) or stable coronary artery disease (CAD). For diabetic patients with ACS, LDL-C should be ＜55 mg/ dL. Several novel agents have become available as adjunctive treatment of FH to reduce LDL-C levels. For example, mipomersen is an antisense oligonucleotide (ASO) inhibitor of apolipoprotein B (Apo B). Lomitapide can inhibit the microsomal triglyceride transfer protein (MTP). Evolocumab, alirocumab, and bococizumab are proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors. Further studies are necessary to confirm the effects of these aforementioned agents on clinical outcomes.

關鍵字

Atherosclerotic cardiovascular disease ； Statin ； Familial hypercholesterolemia

並列摘要

他汀(statin)類藥物一直是血脂異常患者和預防動脈粥樣硬化性心血管疾病(ASCVD)的主要治療方法。針對預防ASCVD的statin治療，2013年美國心臟病學會/美國心臟協會(ACC/AHA)的血脂治療準則提出了四大受益族群，包括：已有臨床ASCVD病人，低密度膽固醇(LDL-C) ≥ 190 mg/dL，糖尿病，以及預測10年ASCVD風險≥ 7.5%者。此外，2013年ACC/AHA血脂治療準則也建議使用不同的statin劑量強度來治療不同風險類別的病人，但卻沒有提出建議的LDL-C治療目標。2016年歐洲心臟學會(ESC)和歐洲動脈粥樣硬化協會(EAS)的血脂治療準則提出了SCORE風險評估系統。對於非常高風險(very high-risk)，高風險(high-risk)和中度風險(moderate-risk)的患者，LDL-C的治療目標分別為＜70 mg/dL，＜100 mg/dL和＜115 mg/dL。而2017年台灣血脂治療準則明確界定了高危病人和LDL-C的治療目標。對於周邊動脈疾病(PAD)，腦血管疾病，DM和家族性高膽固醇血症(FH)患者，建議LDL-C須＜100 mg/dL，而急性冠心症(ACS)或穩定性冠狀動脈疾病(CAD)病人則建議LDL-C須＜70 mg/dL。對於ACS且合併DM之病人，LDL-C應＜55 mg/dL。目前已有幾種新型藥物用於FH的輔助治療，與statin類藥物併用，進一步降低血液中的LDL-C。Mipomeren是載脂蛋白(Apo B)的反寡核苷酸(ASO)抑製劑。Lomitapide可抑制微粒體甘油三酯轉運蛋白(MTP)。Evolocumab，alirocumab和bococizumab是前蛋白轉化酶枯草桿菌蛋白酶/kexin 9型(PCSK9)抑製劑。上述新型藥物是否可以預防臨床不良心血管事件仍待進一步的研究。