New Therapeutic Approaches in Treatment of Dyslipidaemia—A Narrative Review

Abstract

Dyslipidaemia is a well-known risk factor for the development of cardiovascular disease, a leading cause of morbidity and mortality in developed countries. As a consequence, the medical community has been dealing with this problem for decades, and traditional statin therapy remains the cornerstone therapeutic approach. However, clinical trials have observed remarkable results for a few agents effective in the treatment of elevated serum lipid levels. Ezetimibe showed good but limited results when used in combination with statins. Bempedoic acid has been thoroughly studied in multiple clinical trials, with a reduction in LDL cholesterol by approximately 15%. The first approved monoclonal antibodies for the treatment of dyslipidaemia, PCSK9 inhibitors, are currently used as second-line treatment for patients with unregulated lipid levels on statin or statin combination therapy. A new siRNA molecule, inclisiran, demonstrates great potential, particularly concerning compliance, as it is administered twice yearly and pelacarsen, an antisense oligonucleotide that targets lipoprotein(a) and lowers its levels. Volanesorsen is the first drug that was designed to target chylomicrons and lower triglyceride levels, and olezarsen, the next in-line chylomicron lowering agent, is currently being researched. The newest possibilities for the treatment of dyslipidaemia are ANGPTL3 inhibitors with evinacumab, already approved by the FDA, and EMA for the treatment of familial hypercholesterolemia. This article provides a short summary of new agents currently used or being developed for lipid lowering treatment.

Mechanism of action and therapeutic use of bempedoic acid in atherosclerosis and metabolic syndrome

“…Together with poor therapeutic adherence also underestimation of cardiovascular risk by both healthcare professionals and patients lead to failure in reaching therapeutic targets. Two new cholesterol-lowering drugs, which have recently received US FDA and European EMA approval, could foster therapeutic adherence ( 15 , 16 ). Inclisiran is an inhibitor of PCSK9 synthesis with a biannual subcutaneous administration performed by the healthcare professional.…”

Clinical impact of genetic testing for lipid disorders

“…Dyslipidemias are classified as primary or familiar dyslipidemias, caused by a genetic defect of a single gene (monogenic) or multiple genes (polygenic), and secondary due to underlying diseases [e.g. type 2 diabetes mellitus (T2DM), hypothyroidism, chronic kidney disease (CKD), and so on] and medications [11,12,13 ▪ ].…”

“…The use of combination therapy, particularly with all three drugs, including PCSK9i, is associated with greater odds of having LDL-C in desired range [30]. Among the newly developed PCSK9is is inclisiran, a small interfering RNA (siRNA) molecule that reduces the production of PCSK9 and lowers LDL-C level reduction by 51% when used together with other LLTs but there are also bempedoic acid, lomitapide and newly approved drugs (as evinacumab) and drugs in pipeline targeting dyslipidemias [11,21 ▪▪ ,36]. Individuals with severe and unresponsive elevations in LDL-C will require extracorporeal removal of LDL-C (lipoprotein apheresis), but its use is also unequally distributed due to limited availability and cost [21 ▪▪ ].…”

Attenuation of Hyperlipidemia by Medicinal Formulations of Emblica officinalis Synergized with Nanotechnological Approaches

“…Additionally, hypercholesterolemia manifests nephrotic syndrome, a common pathway for the synthesis of cholesterol, and albumin lowers oncotic pressure, resulting in increased cholesterol synthesis [25]. Several medications, including progestins, thiazide diuretics, glucocorticoids, Î2 blockers, isotretinoin, protease inhibitors, cyclosporine, mirtazapine, and sirolimus, have been reported by Hill and Bordoni [26] to increase lipid levels as secondary forms of hyperlipidemia.…”