Dyslipidemia, particularly increased low-density lipoprotein cholesterol (LDL-C) levels, are associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD) events. There is an unmet need for ASCVD risk reduction even with the optimal use of statin therapy, which has led to an ongoing search for novel targets for cholesterol reduction to decrease ASCVD events.

Objectives:

The main aim of this review was to summarize current evidence on approved and emerging non-statin lipid-lowering therapies.

Methods and Materials:

Recent literature on U.S. FDA approved non-statin lipid-lowering therapies and evolving lipid-lowering drugs currently under development was reviewed.

Results and Discussion:

In the past 20 years, the emergence of non-statin cholesterol-lowering drugs has changed the landscape of dyslipidemia management. Food and Drug Administration approval of non-statin lipid-lowering therapies such as ezetimibe, proprotein convertase subtilisin/Kexin type 9 (PCSK9) inhibitors (evolocumab, alirocumab), bempedoic acid and combination of bempedoic acid and ezetimibe, evinacumab and other triglyceride-lowering agents (eg, icosapent ethyl) has emerged. The European Commission has also recently approved inclisiran for treatment of hypercholesterolemia and mixed hypercholesterolemia even though FDA has put the approval of this drug on hold. Recent guidelines have incorporated PCSK9 inhibitors to treat patients with primary hyperlipidemia and patients with very high-risk ASCVD, who could not achieve adequate lipid-lowering with combination therapy of maximally tolerated statin and ezetimibe. Icosapent ethyl use as an adjunct therapy to statins is also recommended to reduce the risk of ASCVD in patients with hypertriglyceridemia.

Conclusion:

Despite cost limitations, the uptake of PCSK9 inhibitors is increasing. Approval of bempedoic acid alone or in combination with ezetimibe has provided additional oral lipid-lowering drug alternatives to ezetimibe. Various lipid-lowering drug targets are under investigation.

中文翻译：

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非他汀类降脂治疗综述

血脂异常，尤其是低密度脂蛋白胆固醇 (LDL-C) 水平升高，与动脉粥样硬化性心血管疾病 (ASCVD) 事件的风险增加有关。即使优化使用他汀类药物治疗，降低 ASCVD 风险的需求仍未得到满足，这导致人们不断寻找降低胆固醇的新靶点以减少 ASCVD 事件。

目标：

本综述的主要目的是总结目前已批准和新兴的非他汀类降脂疗法的证据。

方法和材料：

回顾了美国 FDA 批准的非他汀类降脂疗法和目前正在开发的不断发展的降脂药物的最新文献。

结果和讨论：

在过去的 20 年中，非他汀类降胆固醇药物的出现改变了血脂异常管理的格局。美国食品药品监督管理局批准非他汀类降脂疗法，如依折麦布、前蛋白转化酶枯草溶菌素/Kexin 9 型 (PCSK9) 抑制剂（evolocumab、alirocumab）、bempedoic acid 以及 bempedoic acid 和依折麦布的组合、evinacumab 和其他降甘油三酯药剂（例如，二十碳五烯酸乙酯）已经出现。欧盟委员会最近也批准了 inclisiran 用于治疗高胆固醇血症和混合性高胆固醇血症，尽管 FDA 已暂停对该药物的批准。最近的指南已将 PCSK9 抑制剂纳入原发性高脂血症患者和高危 ASCVD 患者的治疗，最大耐受的他汀类药物和依折麦布联合治疗不能达到充分降脂效果的患者。还建议使用二十碳五烯酸作为他汀类药物的辅助治疗，以降低高甘油三酯血症患者发生 ASCVD 的风险。

结论：

尽管有成本限制，PCSK9 抑制剂的使用仍在增加。bempedoic acid 单独或与依折麦布联合使用的批准为依折麦布提供了额外的口服降脂药物替代品。各种降脂药物靶点正在研究中。