Abstract
Lipid-lowering treatment is a part of the prevention and treatment of vascular diseases caused by atherosclerosis. We need new strategies for modifying plasma lipoprotein levels in light of new findings that reduce target lipid levels even further, as well as the growing population of patients for whom existing treatments cannot be offered.
The spectrum of existing drugs (new statins) is widening; pharmacological treatments (recombinant lipoprotein-bound statins) and improved forms of established drugs (selective PPARalpha receptor modulators) are coming. The new procedures include fixed combinations of established drugs improving adherence and intensifying the lipid-modifying effects (statin + ezetimibe).
The portfolio of lipid-lowering therapies today also includes monoclonal antibodies against PCSK9 (PCSK9 inhibitors). The main direction of future development is biotechnology using the principle of antisense therapy, i.e. the use of specific oligonucleotide sequences blocking the translation of the selected protein.
These targeted therapies targeting, for example, apolipoprotein B, apolipoprotein CIII or lipoprotein (a) are in various stages of clinical trials. A similar (but not identical) principle is the use of RNA silencing - interference with gene expression using short stretches of double-stranded RNA (e.g. inclisiran siRNA against PCSK9).
Innovations in the field of hypolipidaemic pharmacotherapy in our country may also include inhibitors of microsomal triglyceride transfer protein (approved for use in homozygotes for familial hypercholesterolaemia and experimentally also for familial chylomicronaemia). The small molecule ATP citrate lyase inhibitor, bempedoic acid, decreases LDL-C by a further 20% over and above the reduction achievable by a statin.
All these new directions must be directed toward the common main goal of reducing the incidence of cardiovascular and gastrointestinal complications of dyslipidaemia. Clinical research also aims to prove these effects.