2022 台灣版高血脂治療指引-針對心血管疾病高風險族群 3.ACS/CAD PCSK9 亞洲新證據

2025-12-09 14:102022 focused update of the 2017 Taiwanlipid guidelines for high risk patients:Coronary artery disease, peripheral arterydisease and ischemic stroke

下面中文使用google自動翻譯


ACS/CAD
PCSK9抑制劑新數據


臨床試驗評估了使用PCSK9抑制劑（一種新型強效的LDL-C降低療法）將LDL-C水平降至<70 mg/dL的益處。 PCSK9抑制劑單一治療可降低60%的LDL-C，而PCSK9抑制劑合併高強度他汀類藥物治療可使LDL-C降低高達75%。 ⁶ 目前台灣地區可用的PCSK9抑制劑包括evolocumab和alirocumab。在PCSK9抑制劑的結局試驗，即FOURIER和ODYSSEY OUTCOMES研究中，已證實較低的LDL-C值能夠降低冠心病/急性冠狀動脈綜合症（CAD/ACS）患者發生主要不良心血管事件（MACE）的風險。 ^2,3 在FOURIER研究中，對於既往有心肌梗塞、非出血性中風或症狀性週邊動脈疾病史的穩定型動脈粥樣硬化性心血管疾病（ASCVD）患者，依洛尤單抗合併他汀類藥物治療可將LDL-C水平中位數降低至30 mg/dL（四分位數間距19-4666000 mg/dL（BLDL19-460000 mg/dL（BLDL19-46），他為四分位間距19-46960000 mg/dL（BLDL19-466000C)，C30909000 mg/dL（BLDL19-4609000C），他為第96000 mg/dL（BLDL19-4666000C)。 mg/dL的患者相比，MACE風險顯著降低15%。 ² 在ODYSSEY OUTCOMES研究中，對於先前1-12個月內發生過急性冠狀動脈症候群的患者，阿利西尤單抗合併他汀類藥物治療與僅接受他汀類藥物治療的患者相比，MACE風險顯著降低15%。 ³在接受阿利西尤單抗合併他汀類藥物治療的患者組中，4週和48週追蹤時的低密度脂蛋白膽固醇（LDL-C）水準分別為40和53 mg/dL，而單一他汀類藥物組則分別為93和101 mg/dL。儘管PCSK9抑制劑具有臨床療效，但由於其價格昂貴，成本效益已成為一個主要問題，限制了這些藥物在台灣的使用。 ⁷
對於高風險 CAD/ACS 患者，專注於使用 PCSK9 抑制劑以達到更低的 LDL-C 目標值，可能會帶來最大的臨床效益並提高成本效益。在 FOURIER 研究中，研究人員對病情穩定的 ASCVD 患者進行了亞組分析，包括 (1) 先前有心肌梗塞病史的患者和 (2) 有症狀性下肢週邊動脈疾病 (PAD) 的患者。 ^8-10 結果顯示，近期發生心肌梗塞（< 1 年）、既往發生過 2 次心肌梗塞、存在多支血管冠狀動脈疾病（2 支大血管狹窄 40%）以及總共發生過 2 次心肌梗塞、存在多支血管冠狀動脈疾病（2 支大血管狹窄 40%）以及總共發生 2 次心肌梗塞、存在多支血管冠狀動脈疾病（2 支大血管狹窄 40%）以及總共有症狀性 PAD 的患者，發生主要不良心血管事件 (MACE) 的風險更高，並且符合這些條件減少的患者，發生主要不良心血管事件 (MACE) 的風險更高，並且與不符合這些條件的患者相比，BACEC-BACE.風險降低幅度更大。 ^8-10 在 FOURIER 研究中，糖尿病亞組分析顯示，PCSK9 抑制劑降低 MACE 風險的效果在糖尿病患者和非糖尿病患者之間幾乎相同。 ¹¹ 在 ODYSSEY OUTCOMES 研究中，研究人員對近期發生急性冠狀動脈綜合症 (ACS) 的患者進行了亞組分析，包括 (1) 多血管疾病患者（冠狀動脈疾病合併 PAD 或頸動脈狹窄）和 (2) 糖尿病患者。 ^12,13 研究發現，這些患者的風險更高。 MACE 和使用阿利西尤單抗進行強化 LDL-C 降低治療可帶來更大的風險降低。 ^12,13 正如 2017 年指南建議 ACS 和糖尿病患者設定較低的 LDL-C 目標值一樣，這些研究表明，對於 CAD/ACS 的高風險族群，強化 LDL-C 降低治療以達到更低的 LDL-C 目標值可能獲得更多臨床獲益。事實上，2018 年美國心臟協會/美國心臟病學會膽固醇指南¹⁴ 也提出了類似的觀點。在這個 2018 年美國指引中，曾經有多次主要 ASCVD 事件史的患者，包括近期 ACS（過去 12 個月內）、過去 MI 史、過去缺血性中風史和症狀性 PAD，被認為是極高風險族群，建議強化 LDL-C 降低治療。 ¹⁴




推薦


CAD/ACS 患者的 LDL-C 目標值為 < 70 mg/dL（COR I，LOE B）。


除了 ACS 合併糖尿病外，對於 CAD/ACS 高風險患者，包括近期發生 MI（<12 個月）、2 次先前 MI、多支血管 CAD 或伴隨 PAD（包括肢體或頸動脈）的患者，可考慮將 LDL-C 目標值設定為 < 55 mg/dL（COR IIa，LOE B）。


ACS/CAD
New PCSK9 inhibitor data


The benefit of an even lower LDL-C level <70 mg/dL was evaluated in clinical trials using PCSK9 inhibitor which is a novel and powerful class of LDL-C lowering therapy. PCSK9 inhibitor monotherapy provides 60% LDL-C reduction and PCSK9 inhibitor plus high-intensity statin decrease LDL-C up to 75%.6 Currently available PCSK9 inhibitors in Taiwan are evolocumab and alirocumab. The benefits of even lower LDL-C values to reduce the risk of major adverse cardiovascular events (MACE) in CAD/ACS were demonstrated in the outcome trials of PCSK9 inhibitors, the FOURIER and ODYSSEY OUTCOMES studies.2,3 In stable ASCVD with a prior history of MI, nonhemorrhagic stroke, or symptomatic PAD in the FOURIER study, evolocumab plus statin reduced the LDL-C level to a median of 30 mg/ dL (interquartile range 19e46 mg/dL) and obtained a 15% significant risk reduction of MACE compared with those given statin therapy only with an LDL-C level of 92 mg/ dL.2 In patients with recent ACS in previous 1e12 months in the ODYSSEY OUTCOMES study, alirocumab plus statin was associated with a 15% significant risk reduction of MACE compared with statin only group.3 The mean achieved LDL-C level was 40 and 53 mg/dL at 4 weeks and 48 weeks follow-up in the alirocumab plus statin group compared to 93 and 101 mg/dL in the statin only group. Despite their clinical efficacy, due to the high drug price, the cost-effectiveness of PCSK9 inhibitors becomes a major problem and limits the use of these drugs in Taiwan.7
Focusing the use of PCSK9 inhibitors to achieve a lower LDL-C target in CAD/ACS with higher risk is likely to provide maximal clinical benefit and improve the costeffectiveness. In the FOURIER study with stable ASCVD patients, subgroup analyses were performed in (1) patients with prior MI and (2) patients with symptomatic lower extremity PAD.8e10 It turns out that patients with a recent MI < 1 year, 2 prior MIs, presence of multivessel CAD (40% stenosis in 2 large vessels), and concomitant symptomatic PAD were at higher risk of MACE and obtained greater risk reduction from a lower LDL-C level achieved with evolocumab than those without these conditions.8e10 For diabetic subgroup analysis in the FOURIER study, the risk reduction of MACE from PCSK9 inhibitor was almost similar between those with and without diabetes.11 In the ODYSSEY OUTCOMES study with recent ACS patients, subgroup analyses were performed in (1) patients with polyvascular disease (CAD plus PAD or carotid stenosis) and (2) patients with diabetes.12,13 The studies found these patients were at higher risk of MACE and intensive LDL-C lowering with alirocumab caused a larger risk reduction.12,13 Just like a lower LDL-C target for ACS and diabetes recommended in the 2017 guideline, these studies indicate that more intensive LDL-C lowering therapy to achieve an even lower LDL-C target in these very high risk groups of CAD/ACS could obtain more clinical benefits. Actually, the similar concept was also raised in the 2018 American Heart Association/American College of Cardiology Cholesterol Guideline.14 In this 2018 American guideline, patients with a history of multiple major ASCVD events, including recent ACS (within the past 12 months), history of MI, history of ischemic stroke and symptomatic PAD, are considered at very high risk and more intensive LDL-C reduction is recommended.14




Recommendation


The LDL-C target is < 70 mg/dL in patients with CAD/ACS (COR I, LOE B).


In addition to ACS plus diabetes, CAD/ACS at very high risk, including those with recent MI (<12 months), 2 prior MIs, multivessel CAD, or concomitant PAD (including extremity or carotid artery), a lower target of LDL-C < 55 mg/dL can be considered (COR IIa, LOE B).