A Look Beyond Statins and Ezetimibe: a Review of Other Lipid-Lowering Treatments for Cardiovascular Disease Prevention in High-Risk Patients

Purpose of Review There has been significant progress made during the last few decades in the management of atherosclerotic cardiovascular disease (ASCVD). Despite this, residual risk remains an unmet need for secondary prevention and high-risk primary prevention patients. First onset and recurrent cardiovascular events remain a major issue despite recommendations for a healthy lifestyle and current optimal medical therapy, which includes the use of maximally tolerated statin therapy plus or minus add-on ezetimibe therapy. Recent Findings These findings have led to the development of new treatments that modulate lipid targets in order to improve prognosis of these patients at highest ASCVD risk. These include inhibitors of proprotein convertase subtilisin/kexin type 9 (evolocumab and alirocumab), an inhibitor of adenosine triphosphate citrate lyase (bempedoic acid), and a high-dose omega-3 formulation (icosapent ethyl), which have been evaluated in large phase III randomized clinical trials and/or currently undergoing continued study. The clinical efficacy of these drugs and their application in cardiovascular prevention are discussed in this review article. Of note, there are other novel lipid-lowering therapeutics with potential cardiovascular benefit, not discussed in this review, that include inhibitors of lipoprotein (a), apolipoprotein CIII, and angiopoietin-like 3. These drugs may also play a future role in reducing residual lipid-mediated ASCVD risk, if efficacy and safety confirmed in cardiovascular outcome trials. Summary In this review, we provide an overview of the current knowledge regarding treatment with several new lipid strategies for high-risk patients, along with suggestions on their use in ASCVD prevention management.