Department of Pharmacy Practice, College of Pharmacy, 105956Gulf Medical University, Ajman, United Arab Emirates.
Department of Pharmaceutical Sciences, College of Pharmacy, 105949Al Ain University, Al Ain, Abu Dhabi, United Arab Emirates.
J Cardiovasc Pharmacol Ther. 2021 Sep;26(5):437-452. doi: 10.1177/10742484211002943. Epub 2021 Apr 9.
The main aim of this review was to summarize current evidence on approved and emerging non-statin lipid-lowering therapies.
Recent literature on U.S. FDA approved non-statin lipid-lowering therapies and evolving lipid-lowering drugs currently under development was reviewed.
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.
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.
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治疗的证据。
回顾了美国食品和药物管理局批准的非他汀类降脂治疗药物和目前正在开发的新兴降脂药物的最新文献。
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。非他汀类降脂治疗药物，如依折麦布、前蛋白转化酶枯草溶菌素/柯萨奇蛋白酶 9（PCSK9）抑制剂（依洛尤单抗、阿利罗库单抗）、贝匹莫德酸和贝匹莫德酸与依折麦布的联合制剂、evinacumab 以及其他降低甘油三酯的药物（如icosapent ethyl）已获得批准。尽管美国食品和药物管理局已暂停批准该药物，但欧洲委员会最近也批准 inclisiran 用于治疗高胆固醇血症和混合性高胆固醇血症。最近的指南已将 PCSK9 抑制剂纳入治疗原发性高脂血症和极高危 ASCVD 患者的方案中，这些患者不能通过最大耐受剂量他汀类药物和依折麦布联合治疗充分降低血脂。还建议将icosapent ethyl 作为他汀类药物的辅助治疗，以降低高甘油三酯血症患者的 ASCVD 风险。
尽管存在成本限制，但 PCSK9 抑制剂的应用正在增加。贝匹莫德酸单独或与依折麦布联合批准为依折麦布提供了额外的口服降脂药物选择。各种降脂药物靶点正在研究中。
