Umbrella Review on Non-Statin Lipid-Lowering Therapy

Abstract

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.