Novel Experimental Agents for the Treatment of Hypercholesterolemia
Open Access
- 1 February 2021
- journal article
- review article
- Published by Taylor & Francis Ltd in Journal of Experimental Pharmacology
- Vol. ume 13, 91-100
- https://doi.org/10.2147/jep.s267376
Abstract
Abstract: Atherosclerotic cardiovascular diseases (ASCVD) are still the leading cause of morbidity and mortality in most developed countries and even more in developing countries. Dyslipidemia is a well known main risk factor for ASCVD. Lipid-lowering treatment, particularly lowering LDL-cholesterol (LDL-C), can decrease the risk for ASCVD. New data and guidelines based upon them suggest that we should go with LDL-C levels as low as we can. Therefore, conventional lipid lowering agents (statins and statins+ezetimibe) are not enough mainly because of poor compliance and statin intolerance which is in the real world mostly pseudo-intolerance. PCSK9 inhibitors provided a new hope to further decrease LDL-C but are still expensive, they have to be injected subcutaneously twice a month and their long-lasting adverse effects are not known. Therefore, there is a constant need to develop novel, more potent, more safe, less expensive, more user friendly regimens of hypolipemic agents (bempedoic acid, selective PPAR alpha receptor modulators etc). One of the ways to overcome poor compliance and increase the potency of therapy with less adverse effects are fixed combinations of established drugs (statin+ezetimibe). The future of hypolipemic agents is based on antisense therapy, ie. the use of specific oligonucleotide sequences blocking the translation of the selected protein (targeting apolipoprotein CIII, lipoprotein (a), apolipoprotein B) or RNA silencing technique (PCSK9 mRNA) and are in various stages of clinical trials. Some of them are almost ready to use in everyday clinical practice. High risk and very high risk patients (eg. familial hypercholesterolemia, familial severe chylomicronemia syndrome) will benefit most. The aim of this review is to inform about novel hypolipemic agents – potent and safe drugs for dyslipidemia which should reduce the risk of ASCVD.Keywords
This publication has 62 references indexed in Scilit:
- Resistance and intolerance to statinsNutrition, Metabolism and Cardiovascular Diseases, 2014
- Statins in the primary prevention of cardiovascular diseaseNature Reviews Cardiology, 2013
- Ezetimibe therapy: mechanism of action and clinical updateVascular Health and Risk Management, 2012
- Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170 000 participants in 26 randomised trialsThe Lancet, 2010
- Lipoprotein(a) as a cardiovascular risk factor: current statusEuropean Heart Journal, 2010
- Low LDL-C Levels and Cancer: Reassuring But Still Not DefinitiveJournal of the American College of Cardiology, 2008
- High-Dose Atorvastatin vs Usual-Dose Simvastatin for Secondary Prevention After Myocardial InfarctionThe IDEAL Study: A Randomized Controlled TrialJAMA, 2005
- Mutations in PCSK9 cause autosomal dominant hypercholesterolemiaNature Genetics, 2003
- Identification of a Mammalian Angiopoietin-Related Protein Expressed Specifically in LiverGenomics, 1999
- Epidemiology of coronary heart disease: The Framingham studyThe American Journal of Medicine, 1984