Abstract
Lipid-lowering treatment is a part of prevention and treatment of vascular diseases caused by atherosclerosis. We need new strategies for modifying plasma lipoprotein levels in the light of new findings that reduce target lipid levels further lower, 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 lipoproteins-bound statins), improved forms of established drugs (selective PPARα receptor modulators) are coming. The new procedures include fixed combinations of established drugs improving adherence and intensifying 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 so-called antisense therapy, i.e. the use of specific oligonucleotide sequences blocking the translation of the selected protein.
These novel therapies targeting, for example, apolipoprotein B, apolipoprotein CIII, or lipoprotein(a) are in various stages of clinical trials. A simi-lar (but not identical) principle is the use of RNA silencing - interference with gene expression using short sequences of double-stranded RNA (e.g. inclisiran siRNA against PCSK9).
Innovations in the field of hypolipidemic pharmacotherapy in our country may also be inhibitors of microsomal triglyceride transfer protein (approved for use in homozygotes for familial hypercholesterolemia and experimentally also for familial chylomicronemia). 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.
In a broader sense, the novelty of hypolipidemic pharmacotherapy includes treatment options for some rare metabolic diseases (eg. enzyme replacement therapy for acid lysosomal lipase deficiency) manifested by lipoprotein metabolism abnormalities. All these new directions must aim at the common main goal of reducing the incidence of cardiovascular and gastrointestinal complications of dyslipidemia.
Clinical research also aims to prove these effects.