Figure 10.

Main therapeutic options (current and in the pipeline) for TRL dyslipidemia beyond lifestyle changes. In the past few years, elegant research on animals and loss of function studies in humans has earmarked both apoCIII and ANGPTL3 as pharmacological targets. Monoclonal antibodies and inhibitors of their translation have been developed and have gone through phase one to three trials, in the beginning especially for familial hypertriglyceridemias. (1) For ApoCIII, an antisense oligonucleotide (ASO), volanesorsen (2) proved very effective to reduce TGs but had side effects. The new liver-targeted Olezarsen has fewer side effects, and it is very effective. Several trials are ongoing. ANGPTL3: Three approaches have been developed for the inhibition of ANGPTL3, ASO, small-interference RNA (siRNA), and monoclonal antibody (mab). (3) Vupanorsen is an N-AcGal liver-targeted ASO. (4) ARO-ANG3 is an N-AcGal liver-targeted siRNA, the latest addition to the armamentarium and (5) Evinacumab is a promising monoclonal antibody that provides up to 83% reduction in TGs and reduces LDL cholesterol. Ongoing trials for the three approaches are taking place. Other approaches beyond lifestyle changes are the classics (6) Omega-3 fatty acids, whose mode of action is pleiotropic. EPA has proven to be effective in residual risk reduction in cardiovascular disease through the REDUCEIT trial with some controversy with the results from the STRENGTHS trial. (7) PPAR alpha inhibitors. The selective PPAR alpha inhibitor Pemafibrate has just failed to provide an end-point reduction in cardiovascular disease residual risk management, as shown by the PROMINENT trial. The figure was partly generated using Servier Medical Art, provided by Servier, licensed under a Creative Commons Attribution 3.0 unported license.