Novel lipid-lowering agents targeting PCSK9, ACLY, ANGPTL3, apoC3, and Lp(a) provide promising therapeutic options for reducing residual atherosclerotic cardiovascular disease risk beyond statins.
Novel lipid-lowering therapies targeting PCSK9, ACLY, PPARα, ApoC3, and ANGPTL3 offer promising options for reducing residual cardiovascular risk in patients with dyslipidemia despite optimal statin therapy.
Statins are the cornerstone of the prevention and treatment of atherosclerotic cardiovascular disease (ASCVD). However, even under optimal statin therapy, a significant residual ASCVD risk remains. Therefore, there has been an unmet clinical need for novel lipid-lowering agents that can target low-density lipoprotein cholesterol (LDL-C) and other atherogenic particles. During the past decade, several drugs have been developed for the treatment of dyslipidemia. Inclisiran, a small interfering RNA that targets proprotein convertase subtilisin/kexin type 9 (PCSK9), shows comparable effects to that of PCSK9 monoclonal antibodies. Bempedoic acid, an ATP citrate lyase inhibitor, is a valuable treatment option for the patients with statin intolerance. Pemafibrate, the first selective peroxisome proliferator-activated receptor alpha modulator, showed a favorable benefit-risk balance in phase 2 trial, but the large clinical phase 3 trial (PROMINENT) was recently stopped for futility based on a late interim analysis. High dose icosapent ethyl, a modified eicosapentaenoic acid preparation, shows cardiovascular benefits. Evinacumab, an angiopoietin-like 3 (ANGPTL3) monoclonal antibody, reduces plasma LDL-C levels in patients with refractory hypercholesterolemia. Novel antisense oligonucleotides targeting apolipoprotein C3 (apoC3), ANGPTL3, and lipoprotein(a) have significantly attenuated the levels of their target molecules with beneficial effects on associated dyslipidemias. Apolipoprotein A1 (apoA1) is considered as a potential treatment to exploit the athero-protective effects of high-density lipoprotein cholesterol (HDL-C), but solid clinical evidence is necessary. In this review, we discuss the mode of action and clinical outcomes of these novel lipid-lowering agents beyond statins.
Kim et al. (Thu,) conducted a review in Dyslipidemia and Atherosclerotic Cardiovascular Disease. Novel lipid-lowering agents was evaluated. Novel lipid-lowering agents targeting PCSK9, ACLY, ANGPTL3, apoC3, and Lp(a) provide promising therapeutic options for reducing residual atherosclerotic cardiovascular disease risk beyond statins.