Tackling Residual Atherosclerotic Risk in Statin-Treated Adults: Focus on Emerging Drugs

Kohei Takata; Stephen J. Nicholls


Am J Cardiovasc Drugs. 2019;19(2):113-131. 

In This Article

Abstract and Introduction


Epidemiological studies and meta-analyses have consistently suggested the importance of lowering low-density lipoprotein cholesterol (LDL-C) to reduce cardiovascular (CV) events. However, these studies and mechanistic studies using intracoronary imaging modalities have reported patients who continue to experience CV events or disease progression despite optimal LDL-C levels on statins. These findings, including statin intolerance, have highlighted the importance of exploring additional potential therapeutic targets to reduce CV risk. Genomic insights have presented a number of additional novel targets in lipid metabolism. In particular, proprotein convertase subtilisin/kexin type 9 inhibitors have rapidly developed and recently demonstrated their beneficial impact on CV outcomes. Triglyceride (TG)-rich lipoproteins have been recently reported as a causal factor of atherosclerotic cardiovascular disease (ASCVD). Indeed, several promising TG-targeting therapies are being tested at various clinical stages. In this review, we present the evidence to support targeting atherogenic lipoproteins to target residual ASCVD risk in statin-treated patients.


Atherosclerotic cardiovascular disease (ASCVD) remains a leading cause of morbidity and mortality despite continuous efforts for the improvement of cardiovascular (CV) care.[1] In addition to the established benefits of statins for reducing ASCVD risk, recently the Improved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT) demonstrated an incremental benefit of low-density lipoprotein cholesterol (LDL-C) lowering with ezetimibe on ASCVD events.[2] However, many patients who achieved target LDL-C levels with lipid-lowering therapies (LLTs) still experience CV events or progression of coronary atherosclerosis,[3] underscoring the importance of novel strategies for lipid management in high ASCVD risk patients. Recent findings in genetic studies have established causal roles in ASCVD and developed therapeutic approaches. In this review, we focus on novel lipid-modifying drugs that have the potential to control the residual ASCVD risk.