Over the last 3 decades, hypolipidaemic treatment has significantly reduced both 
Cardiovascular (CV) risk and events, with statins being the cornerstone of this 
achievement. Nevertheless, residual CV risk and unmet goals in hypolipidaemic 
treatment make novel options necessary. Recently marketed monoclonal antibodies 
against proprotein convertase subtilisin/kexin type 9 (PCSK9) have shown the way 
towards innovation, while other ways of PCSK9 inhibition like small interfering 
RNA (Inclisiran) are already being tested. Other effective and well tolerated 
drugs affect known paths of lipid synthesis and metabolism, such as bempedoic 
acid blocking acetyl-coenzyme A synthesis at a different level than statins, 
pemafibrate selectively acting on peroxisome proliferator-activated receptor 
(PPAR)- alpha receptors and oligonucleotides against apolipoprotein (a). 
Additionally, other novel hypolipidaemic drugs are in early phase clinical 
trials, such as the inhibitors of apolipoprotein C-III, which is located on 
triglyceride (TG)-rich lipoproteins, or the inhibitors of angiopoietin-like 3 
(ANGPTL3), which plays a key role in lipid metabolism, aiming to beneficial 
effects on TG levels and glucose metabolism. Among others, gene therapy 
substituting the loss of essential enzymes is already used for Lipoprotein 
Lipase (LPL) deficiency in autosomal chylomicronaemia and is expected to 
eliminate the lack of Low- Density Lipoprotein (LDL) receptors in patients with 
homozygous familial hypercholesterolaemia. Experimental data of High-Density 
Lipoprotein (HDL) mimetics infusion therapy have shown a beneficial effect on 
atherosclerotic plaques. Thus, many novel hypolipidaemic drugs targeting 
different aspects of lipid metabolism are being investigated, although they need 
to be assessed in large trials to prove their CV benefit and safety.