| Abstract [eng] |
Justification. Cardiovascular diseases are the leading cause of mortality worldwide. Dyslipidemia is one of the most important cardiovascular risk factors. Currently, hydroxymethylglutaryl–CoA reductase enzyme inhibitors (statins) constitute the cornerstone of dyslipidemia management. However, their use is associated with certain limitations and target lipid levels are not always achieved. In recent years, the identification of novel therapeutic targets and the development of innovative treatment approaches have expanded the possibilities for dyslipidemia management. Aim. To review currently used and the latest drug groups for the treatment of dyslipidemia, their mechanism of action, their role in contemporary treatment algorithms, and aspects of their clinical application, based on scientific literature and the analysis of a clinical case. Methods. The literature review was primarily based on studies published in English between 2016 and 2026, selected from PubMed and Google Scholar databases in accordance with the topic and objectives of the review. Official documents from international regulatory authorities and textbook sources were also included. In total, 117 scientific sources were analyzed. Literature analysis. Statins remain the first – line therapy for hypercholesterolemia, and hypertriglyceridemia. However, their use is frequently associated with muscle – related adverse effects, the risk of which is increased by drug – drug interactions, and genetic factors. Novel low – density lipoprotein – lowering therapies include proprotein convertase subtilisin/kexin type 9 inhibitors – monoclonal antibodies evolocumab and alirocumab – as well as small interfering ribonucleic acid inclisiran. These agents may be prescribed as adjunctive therapy for hypercholesterolemia when lipid – lowering treatment is insufficiently effective, or as an alternative for patients who are intolerant to or decline statin therapy. Bempedoic acid is another new low density lipoprotein – lowering agent, indicated for statin – intolerant patients or as add – on therapy. The angiopoietin – like protein 3 inhibitor evinacumab and the microsomal triglyceride transfer protein inhibitor lomitapide are approved for the treatment of homozygous familial hypercholesterolemia. New triglyceride – lowering therapies include agents targeting apolipoprotein C-III. The antisense oligonucleotides volanesorsen and olezarsen, as well as the small interfering ribonucleic acid agent plozasiran, are approved as adjunctive treatment for patients with familiar chylomicronemia syndrome. Agents targeting lipoprotein(a), including the antisense oligonucleotide pelacarsen and small interfering ribonucleic acid therapies (olpasiran and lepodisiran), are currently in phase III clinical outcomes trials. Case report. We describe a rare combination of genetic variants in APOE, associated with impaired lipoprotein uptake into tissues, and SLCO1B1, which reduce statin uptake into hepatocytes. This combination is linked to severe hypercholesterolemia resistant to conventional therapy, which relies on preserved low density lipoprotein receptor function. This case highlights the need for the development of novel therapies targeting alternative mechanisms. Conclusions. The development of new pharmacological agents is significantly expanding treatment options for dyslipidemia, both for patients with hypercholesterolemia who do not achieve target low density lipoprotein levels with standart therapy and for rare, treatment resistant conditions such as homozygous familial hypercholesterolemia and familiar chylomicronemia syndrome. Furthermore, the first specific therapy targeting lipoprotein(a) is expected to become available in the near future. |
