2022 台灣版高血脂治療指引-針對心血管疾病高風險族群 4 PAD-LDL控制目標

2025-12-09 14:10

2022 focused update of the 2017 Taiwanlipid guidelines for high risk patients:Coronary artery disease, peripheral arterydisease and ischemic stroke

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LDL-C 目標

週邊動脈疾病（PAD）是全身性動脈粥狀硬化的臨床表現。由於動脈粥狀硬化導致下肢動脈狹窄，造成供血不足，進而引起PAD的臨床症狀，包括間歇性跛行、缺血性潰瘍、急性或危重肢體缺血。 ^15,16 PAD患者發生心肌梗塞、缺血性中風和心血管死亡的風險更高。 ^17,18 事實上，PAD患者的心血管事件風險甚至高於冠狀動脈疾病（CAD）患者。 ¹⁹ 由於動脈粥狀硬化是PAD發病機制的主要因素，且其心血管風險較高，因此對PAD患者更積極地治療低密度脂蛋白膽固醇（LDL-C）水平是合理的。一項名為「心臟保護研究」的隨機對照試驗，旨在研究辛伐他汀降低低密度脂蛋白膽固醇（LDL-C）的療效，結果顯示，在接受每日40毫克辛伐他汀治療的外周動脈疾病（PAD）患者中，5年隨訪期間血管事件發生率較安慰劑組降低了22%。 ²⁰ 一項統合分析報告稱，他汀類藥物降低PAD患者的LDL-C水平與全因死亡率降低、非致命性中風發生率降低以及心肌梗塞風險降低的趨勢有關。 ²¹ 降血脂治療降低LDL-C水平還能緩解臨床症狀，提高運動耐力，減緩PAD患者動脈粥狀硬化斑塊的進展。 ^22-24 在斯堪的納維亞辛伐他汀存活研究的事後分析中，接受辛伐他汀治療的患者在5.4年的中位追蹤期內，間歇性跛行發生率較安慰劑組降低了38%。 ²⁵ West等人有研究通報，辛伐他汀合併或不合併依折麥布降低低密度脂蛋白膽固醇（LDL-C）水準可延緩週邊動脈疾病（PAD）病患股淺動脈粥狀硬化斑塊的進展²⁴。基於科學證據，大多數最新指南將PAD歸類為高風險或極高風險，並建議將LDL-C水平控制在<70或55 mg/dL^6,14,26,27。一項韓國回顧性隊列研究評估了LDL-C對接受血管內治療的PAD患者臨床結果的影響²⁸。研究發現，在中位追蹤4.8個月期間，LDL-C<70 mg/dL的患者發生主要不良心血管事件（MACE，包括全因死亡、非致死性心肌梗塞和中風）的風險低於LDL-C≥70 mg/dL的患者。此結果表明，對於亞洲PAD患者而言，將LDL-C控制在<70 mg/dL的目標值也十分重要。大多數指引和臨床研究對症狀性週邊動脈疾病 (PAD) 的定義包括：(1) 有周邊動脈血管重建史；(2) 有因動脈粥狀硬化性疾病導致肢體缺血而截肢的病史；(3) 出現 PAD 臨床症狀，且影像學檢查證實週邊動脈狹窄程度 > 50%。對於這些定義明確的症狀性 PAD 患者，強化低密度脂蛋白膽固醇 (LDL-C) 控制是有益的。

PAD

LDL-C target

PAD is a clinical manifestation of systemic atherosclerosis. Insufficient blood supply due to atherosclerotic narrowing of lower extremity arteries leads to clinical symptoms of PAD, including claudication, ischemic ulcer and acute or critical limb ischemia.15,16 PAD patients have higher risk of MI, ischemic stroke and cardiovascular mortality.17,18 In fact, the risk of cardiovascular events is even higher in patients with PAD than CAD.19 Because atherosclerosis accounts for the majority of pathogenesis and its high cardiovascular risk, it is reasonable to treat LDL-C more aggressively for PAD patients. A randomized controlled trial, the Heart Protection Study, investigating the efficacy of LDL-C lowering by simvastatin revealed a 22% decrease of vascular events in 5-year follow-up in PAD patients taking simvastatin 40 mg daily compared to those taking placebo.20 A meta-analysis reported that LDL-C lowering by statin in PAD was associated with lower all-cause mortality, lower nonfatal stroke as well as a trend of lower risk of MI.21 LDL-C reduction with lipid-lowering therapy also alleviated clinical symptoms, improved exercise endurance, and slowed down the progression of atherosclerotic plaques in patients with PAD.22e24 In the post hoc analysis of Scandinavian Simvastatin Survival Study, patients receiving simvastatin had a 38% decrease of intermittent claudication than those receiving placebo in a median follow-up of 5.4 years.25 West et al. reported that reduction of LDL-C by simvastatin with or without ezetimibe hold the progression of atherosclerotic plaques in superficial femoral artery in PAD patients.24 Based on the scientific evidence, most of the recent guidelines classify PAD as high risk or very high risk and recommend to achieve a LDL-C level <70 or 55 mg/dL.6,14,26,27 A Korean retrospective cohort study assessed the influence of LDL-C on clinical outcomes in PAD patients receiving endovascular treatment.28 They found patients with LDL-C < 70 mg/dL had lower risk of MACE which was a composite of all-cause mortality, nonfatal MI and stroke than those with LDL-C 70 mg/dL in a median follow-up of 4.8 months. The result implied that achieving a goal of LDL-C < 70 mg/dL is also important in Asian PAD patients. In most guidelines and clinical studies, the definitions of symptomatic PAD include (1) history of peripheral artery revascularization, (2) history of amputation for ischemic limb due to atherosclerotic disease, (3) clinical symptoms of PAD with > 50% stenosis of peripheral arteries confirmed by imaging studies. Intensive LDL-C control is beneficial in these well-defined symptomatic PAD patients.