Contemporary hypolipemic therapy: possibilities of novel hypolipemic drugs in correction of lipid metabolism disorders. Review

Abstract

Dyslipidemia plays a role of significant risk factor for development and progression of cardiovascular diseases. Today several classes of hypolipemic drugs with evidenced effectiveness are used. But some patients don’t tolerate medicines with high efficacy or can’t achieve the targeted blood lipid profile levels even in case of the use of maximal doses or combined therapy. This necessitates the creation of new hypolipidemic agents.
 The review is devoted to discussion of new directions of influence on impaired lipid metabolism through creation of new classes of hypolipemic drugs with some perspectives of effective correction of lipid factors of cardiovascular risk (CVR) in cases of impossibility to achieve the targeted levels of low‑density lipoprotein cholesterol (LDL‑C) or there is a residual CVR caused by elevated serum triglyceride (TG) levels and/or low levels of high‑density lipoprotein cholesterol (HDL‑C).
 Among the novel drugs for hypercholesterolemia (HCE) correction, considerations are given for some mechanisms of action and efficacy of application of proprotein convertase subtilisin‑kexine type 9 (PCSK9) inhibitors as well as bempedoic acid (adenosine triphosphate citrate lyase inhibitor) and inclisiran, a small synthesized interfering ribonucleic acid (RNA) with its ability to blockade genes‑regulators of hepatic PCSK9 activity. The novel agents for hypertriglyceridemia correction, discussed in the review, include icosapent ethyl (a high purified and firm ester of ethyl‑eicosapentoenic acid), pemafibrate (the first selective modulator of α‑receptors activated by peroxisome proliferator), apolipoprotein C‑III (ApoC‑III) inhibitors (volasenorsen, olesarsen), mipomersen (antisense nucleotide for matrix RNA of apolipoprotein B‑100), lomitapide (inhibitor of microsomal TG transfer protein) and inhibitors of angiopoietin‑like protein 3 (ANGPTL3) (evinacumab, vupanorsen). Among the new approaches to HDL‑C elevation an attention is paid to the experimental and clinical investigations of recombinant HDL, agents with recombinant lecithin‑cholesterol‑acyl‑transferase (LCAT), and apolipoprotein A‑I (ApoA‑I) mimetic peptides. For the lowering of blood lipoprotein(a) (LP(a)) level the possibilities of pelacarsen, an antisense oligonucleotide for matrix RNA of apolipoprotein(a) (apo(a)) contained in LP(a) molecule and olpasiran, a small interfering RNA for LP(a) molecule inhibited apo(a) synthesis are uncovered. A high probability of clinical application in the nearest future will have novel drugs approved by US Food and Drug Administration (FDA) and European Medicines Agency (EMA) such as bempedoic acid and inclisiran for HCE correction as well as lomitapide for the treatment of familial HCE.