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Will these new iRNA-based LDL and Lp(a) Lowering Rx Make a Significant Impact on US’ Average Cholest

Impact on US’ Average Cholesterol Level? Probably Not.

J Am Coll Cardiol. 2021 Mar, 77 (12) 1564–1575 New and Emerging Therapies for Reduction of LDL-Cholesterol and Apolipoprotein B: JACC Focus Seminar 1/4 Nick S. Nurmohamed, Ann Marie Navar, and John J.P. Kastelein Abstract Adding to the foundation of statins, ezetimibe and proprotein convertase subtilisin–kexin type 9 inhibitors (PCSK9i), novel, emerging low-density lipoprotein cholesterol (LDL-C)–lowering therapies are under development for the prevention of cardiovascular disease. Inclisiran, a small interfering RNA molecule that inhibits PCSK9, only needs to be dosed twice a year and has the potential to help overcome current barriers to persistence and adherence to lipid-lowering therapies. Bempedoic acid, which lowers LDL-C upstream from statins, provides a novel alternative for patients with statin intolerance. Angiopoetin-like 3 protein (ANGPTL3) inhibitors have been shown to provide potent LDL-C lowering in patients with homozygous familial hypercholesterolemia without major adverse effects as seen with lomitapide and mipomersen, and may reduce the need for apheresis. Finally, CETP inhibitors may yet be effective with the development of obicetrapib. These novel agents provide the clinician the tools to effectively lower LDL-C across the entire range of LDL-C–induced elevation of cardiovascular risk, from primary prevention and secondary prevention to null-null homozygous familial hypercholesterolemia patients. Highlights •Despite current strategies, the burden of atherosclerotic cardiovascular disease remains high. •LDL-C is a major causal risk factor for atherosclerotic cardiovascular disease. •Statins, ezetimibe, and PCSK9 inhibitor monoclonal antibodies are the main pharmacological agents currently used for lowering LDL-C. •Inclisiran, bempedoic acid, ANGPTL3, and CETP inhibitors, which are in different stages of development, have the potential to diminish residual risk related to LDL-C.

Listen to Dr. Fuster’s Audio Message

Why are we not making progress in cardiovascular public health? Perhaps because we are not paying enough for prevention.

Reference: Asymptomatic Atherosclerosis: Pathophysiology, Detection, and Treatment (Google Book Preview) Authors: Morteza Naghavi, M.D. Daniel Berman, M.D. Erling Falk, M.D. Zahi Fayad, Ph.D. Khurram Nasir, M.D. Mathew Budoff, M.D. Harvey Hetch, M.D. P.K. Shah, M.D. Foreward by: Valentin Fuster, M.D., Ph.D.

Data from CDC


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