Despite the substantial reduction in cardiovascular morbidity and mortality after the management of dyslipidemia with statins, residual risk remains even after achieving low-density lipoprotein choles Show more
Despite the substantial reduction in cardiovascular morbidity and mortality after the management of dyslipidemia with statins, residual risk remains even after achieving low-density lipoprotein cholesterol targets. This residual risk appears to be partly attributed to low levels of high-density lipoprotein cholesterol (HDL-C) and high levels of triglycerides (TG). Apolipoprotein C3 (APOC3) is a key regulator of TG metabolism and its targeting may reduce TG levels and cardiovascular risk. We discuss APOC3-targeted experimental treatments for dyslipidemia. There is an emphasis on volanesorsen because it the agent in the most advanced stage of development. M580, a retinoic acid receptor-α specific agonist, an agent in early-stage development is briefly covered. Preclinical data suggest that this agent decreases APOC3 mRNA levels and reduces total cholesterol, TG levels and hepatic lipid accumulation. The effects of this novel therapeutic approach on cardiovascular morbidity and mortality should be determined in randomized controlled trials. The cost of volanesorsen, the unfavorable safety profile and the need for subcutaneous administration present barriers to long-term use. AM580 may hold promise in the management of hypertriglyceridemia but further investigations are necessary to evaluate safety and efficacy. Show less