Therapeutic Agents Targeting Cardiometabolic Risk for Preventing and Treating Atherosclerotic Cardiovascular Diseases

Abstract

Targeting atherogenic lipoprotein levels with statins remains the current cornerstone of atherosclerotic cardiovascular disease (ACVD) management. In patients at high ACVD risk who cannot achieve the desired low-density lipoprotein (LDL) cholesterol target, the addition of compounds such as ezetimibe and proprotein subtilisin/kexin type-9 (PCSK9) inhibitors incrementally lowers cardiovascular risk. New glucose-lowering drugs such as glucacon-like peptide-1 receptor (GLP1R) agonists and sodium-glucose cotransporter-2 (SGLT2) inhibitors were also shown to improve cardiometabolic risk factors and provide cardiovascular benefits in patients with type 2 diabetes. Our objective is to review the role of these agents in the management of patients at high ACVD risk and introduce new and (re)-emerging drugs targeting atherogenic lipoproteins such as LDL (inclisiran, bempedoic acid, etc.), remnant-like particles (fibrates, volanesorsen, and angiopoietin-like protein-3 (ANGPTL3) inhibitors), and lipoprotein(a) (AKCEA-APO[A]L_RX ). The potential role of drugs targeting inflammation (canakinumab, methotrexate, and colchicine) in ACVD risk prevention/management will also be discussed.