As dyslipidemias remain one of the main risk factors for developing cardiovascular disease, the question of maintaining optimal lipid levels with pharmacotherapy remains a subject of interest worldwide. In contrast to conventional pharmacotherapy, human monoclonal antibodies directed against proprotein convertase subtilisin/kexin type 9 (PSCK9) and small interfering RNA- (siRNA-) based drug targeting PCSK9 represent a new strategy for managing lipid disorders and reducing cardiovascular risk. Inclisiran is a long-acting, synthetic siRNA that targets hepatic production of PCSK9 and consequently causes a reduction in LDL-C concentrations by approximately 50% compared to placebo. The structural modification of inclisiran has led to better stability and prolonged biological activity of the drug. The main advantage over conventional pharmacotherapy and anti-PCSK9 monoclonal antibodies is its favorable administration regimen (0–90–180 days), which should lead to much better compliance. Clinical trials conducted so far have confirmed the tolerability and efficacy of inclisiran in long-term PCSK9 and LDL-C level reductions. Moreover, a short-term follow-up on the safety of inclisiran showed a relatively good safety profile of the drug. However, it is still of great importance for ongoing and forthcoming clinical trials to be continued on a larger group of patients in order to assess long-term tolerability, efficacy, and safety of inclisiran.
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.
Exclusive use of amikacin significantly reduced the resistance of GNB isolates to gentamicin and netilmicin, the number of GNB nosocomial bacteremias, and the cost of total antibiotic usage in ICUs.
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