A Look Beyond Statins and Ezetimibe: a Review of Other Lipid-Lowering Treatments for Cardiovascular Disease Prevention i

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LIPIDS (E. MICHOS, SECTION EDITOR)

A Look Beyond Statins and Ezetimibe: a Review of Other Lipid-Lowering Treatments for Cardiovascular Disease Prevention in High-Risk Patients Pierre Sabouret 1 & Denis Angoulvant 2 & Atul Pathak 3 & Francesco Costa 4 & Théo Pezel 5 & Erin D. Michos 6

# Springer Science+Business Media, LLC, part of Springer Nature 2019

Abstract 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. Keywords Residual risk . Lipid-lowering treatments . Bempedoic acid . Eicosapentaenoic acid . PCSK9 inhibitors . Inclisiran

This article is part of the Topical Collection on Lipids * Pierre Sabouret [email protected]; [email protected] 1

Heart Institute, Pitié-Salpétrière Hospital, ACTION-Group, Pierre and Marie Curie University, 47-83 Boulevard de L’Hôpital, 75013 Paris, France

2

Loire Valley Cardiovascular Collaboration & EA4245, CHRU de Tours & Tours University, Tours, France

3

Department of Cardiovascular Medicine, Clinique Pasteur, INSERM 1048, Toulouse, France

4

Department of Clinical and Experimental Medicine, Policlinic “G. Martino”, University of Messina, Messina, Italy

5

Department of Cardiology, La Riboisère Hospital, 2 Rue Ambroise Paré, 75010 Paris, France

6

The Ciccarone Center for the Prevention of Cardiovascular Disease, 600 N Wolfe St, Baltimore, MD 21287, USA

Introd