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This article has been peer reviewed. It is the authors' final version prior to publication in Journal of Cardiovascular Medicine, Volume 16, Issue 1, January 2015, Pages 1-10.

The published version is available at DOI: 10.2459/JCM.0000000000000193. Copyright © Lippincott Williams and Wilkins


Elevated low-density lipoprotein cholesterol (LDL-C) levels are associated with an increased risk for cardiovascular disease (CVD). Statins have been the cornerstone of lipid therapy to lower LDL-C for the past two decades, but despite significant clinical efficacy in a majority of patients, a large residual risk remains for the development of initial or recurrent atherosclerotic CVD. In addition, owing to the side-effects, a significant percentage of patients cannot tolerate any statin dose or a high enough statin dose. Thus, novel therapeutic agents are currently being developed to lower LDL-C levels further. This review will highlight these novel therapeutic agents including antisense oligonucleotides focused on apolipoprotein B, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, and microsomal triglyceride transfer protein inhibitors. For each therapeutic class, an overview of mechanism of action, pharmacokinetic data, and efficacy/safety evidence will be discussed.

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