The wind of change – PCSK9 inhibitors in hypolipidemic treatment. The Polish perspective
DOI:
https://doi.org/10.12775/JEHS.2023.15.01.014Keywords
PCSK9 inhibitors, alirocumab, evolocumab, inclisiranAbstract
Introduction and aim. Cardiovascular diseases are the main cause of mortality in the world. One of the alterable risk factors of ischaemic heart disease is dyslipidemia. Discovery and usage of a new group of drugs - PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitors lead to a decrease of LDL-C (low-density lipoprotein cholesterol) levels in patients who are resistant to standard hypolipidemic therapy. The aim of this paper is to introduce PCSK9 inhibitors and describe their usage in medicine.
Material and methods. A review of the available literature was performed by searching the PubMed and GoogleScholar databases using the following key words: PCSK9 inhibitors; alirocumab; evolocumab; inclisiran.
Analysis of the literature. According to the European Society of Cardiology guidelines for dyslipidemias from year 2019, the main aim of dyslipidemia treatment is LDL-C reduction to target values depending on patient risk levels. It may be achieved in 2 ways, namely, by lifestyle modification or by pharmacological treatment with statins, fibrates and cholesterol absorption inhibitors. However, a therapy with PCSK9 inhibitors may be considered the most effective in certain groups of patients. Evolocumab and alirocumab are 2 representatives of those new drugs, which are allowed for use in 3 scenarios – in patients with familial hypercholesterolemia, in those with high risk of cardiovascular incident, and in those with statin intolerance. The major advantage of the aforementioned drugs is their safety. Since 2021 inclisiran (the first drug in siRNA class) is available for use as a new type of PCSK9 blocker.
Conclusion. PCSK9 inhibitors can be life-saving for patients with a high risk of cardiovascular incidents associated with an elevated level of LDL-C. They reduce LDL-C more efficiently and have fewer side effects in comparison with the other hypolipidemic drugs. Therefore, PCSK9 inhibitors play a very important role in the lipid-lowering treatment.
References
Modrzejewski W, Musiał WJ. Stare i nowe czynniki ryzyka sercowo-naczyniowego – jak zahamować epidemię miażdżycy? [Old and new cardiovascular risk factors - how to stop the epidemic of atherosclerosis?] Forum Zaburzeń Metabolicznych. 2010; 1: 106-114.
Haberka M, Okopień B, Gąsior Z. Najważniejsze zalecenia diagnostyczne i terapeutyczne u chorych z zaburzeniami gospodarki lipidowej [The most important diagnostic and therapeutic recommendations in patients with lipid metabolism disorders] In: Kardiologia po Dyplomie 2012 04.
Mach F, Baigent C, Catapano AL, Koskinas KC, et al.; ESC Scientific Document Group. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J. 2020 Jan 1;41(1). doi: 10.1093/eurheartj/ehz455.
Wożakowska-Kapłon B, Barylski M, Salwa P et al. Zalecenia postępowania w dyslipidemii: propozycje algorytmu dla lekarzy rodzinnych. [Recommendations for dyslipidemia management: algorithm proposals for general practitioners.] Forum Med Rodz. 2012; 6: 261–282.
Visseren FLJ, Mach F, Smulders YM, et al.: 2021 ESC Guidelines on cardiovascular disease prevention in clinical practice. Eur Heart J. 2021, 42, 3227-3337. doi: 10.1093/eurheartj/ehab484.
Podstawa leczenia chorych z hipercholesterolemią rodzinną. [The basis of treatment of patients with familial hypercholesterolaemia.] Krajowe Centrum Hipercholesterolemii Rodzinnej Web site. http://hipercholesterolemia.com.pl/Leczenie_farmakologiczne,19,57.html. Accessed May 10, 2023.
Cybulska B, Kłosiewicz-Latoszek L. Statyny i fibraty w praktyce klinicznej. Zalety i ograniczenia. [Statins and fibrates in clinical practice. Advantages and limitations.] Przewodnik Lekarza/Guide for GPs. 2003:26-35.
Seidah NG. The PCSK9 discovery, an inactive protease with varied functions in hypercholesterolemia, viral infections, and cancer. J Lipid Res. 2021;62:100130. doi: 10.1016/j.jlr.2021.100130.
Banach M, Burchardt P, Chlebus K, et al. Wytyczne PTL/KLRwP/PTK/ PTDL/PTD/PTNT diagnostyki i leczenia zaburzeń lipidowych w Polsce 2021 [PTL/KLRwP/PTK/ PTDL/PTD/PTNT guidelines for diagnosis and treatment of lipid disorders in Poland 2021] Lekarz POZ Suplement. 2021.
Krähenbühl S, et al. Unmet Needs in LDL-C Lowering: When Statins Won't Do! Drugs. 2016 Aug;76(12):1175-90. doi: 10.1007/s40265-016-0613-0.
Bouhairie VE, Goldberg AC. Familial hypercholesterolemia. Cardiol Clin. 2015 May;33(2):169-79. doi: 10.1016/j.ccl.2015.01.001.
Węgrzyn A, Lewandowski P, Taszner M, Gruchała M, Rynkiewicz A. Familial hypercholesterolemia – diagnostic and therapeutic problems of high risk patient. Przewodnik Lekarza/Guide for GPs. 2011:30-37.
Dragan S, Serban MC, Banach M. Proprotein convertase subtilisin/kexin 9 inhibitors: an emerging lipid-lowering therapy? J Cardiovasc Pharmacol Ther. 2015; 20: 157-168. doi: 10.1177/1074248414539562.
Blumenthal DM, Maddox TM, Aragam K et al. Predictors of PCSK9 (Proprotein Convertase Subtilisin/ Kexin Type 9) Inhibitor Prescriptions for Secondary Prevention of Clinical Atherosclerotic Cardiovascular Disease. Circ Cardiovasc Qual Outcomes. 2021: CIRCOUTCOMES120007237. doi: 10.1161/CIRCOUTCOMES.120.007237.
Sabatine MS, Giugliano RP, Keech AC et al. FOURIER Steering Committee and Investigators. Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease. N Engl J Med. 2017; 376: 1713-1722. doi: 10.1056/NEJMoa1615664.
Schwartz GG, Steg PG, Szarek M et al.; ODYSSEY OUTCOMES Committees and Investigators. Alirocumab and Cardiovascular Outcomes after Acute Coronary Syndrome. N Engl J Med. 2018; 379: 2097-2107. doi: 10.1056/NEJMoa1801174.
Macchi C, Ferri N, Sirtori CR et al. Proprotein Convertase Subtilisin/Kexin Type 9: A View beyond the Canonical Cholesterol-Lowering Impact. Am J Pathol. 2021; 191: 1385-1397. doi: 10.1016/j.ajpath.2021.04.016.
Koskinas KC, Windecker S, Pedrazzini G et al. Evolocumab for Early Reduction of LDL Cholesterol Levels in Patients With Acute Coronary Syndromes (EVOPACS). J Am Coll Cardiol. 2019; 74: 2452-2462. doi: 10.1016/j.jacc.2019.08.010.
Leucker TM, Blaha MJ, Jones SR et al. Effect of Evolocumab on Atherogenic Lipoproteins During the Peri- and Early Postinfarction Period: A Placebo-Controlled, Randomized Trial. Circulation. 2020; 142: 419-421. doi: 10.1161/CIRCULATIONAHA.120.046320.
Trankle CR, Wohlford G, Buckley LF et al. Alirocumab in Acute Myocardial Infarction: Results From the Virginia Commonwealth University Alirocumab Response Trial (VCU-AlirocRT). J Cardiovasc Pharmacol. 2019; 74: 266-269. doi: 10.1097/FJC.0000000000000706.
Janikowski K, Lelonek M. 2015. Inhibitory PCSK9 - nowa terapia hipolipemizująca. [PCSK9 inhibitors - a new lipid-lowering therapy.] Folia Cardiologica. 2015; 10, 3: 178–182.
Praluent, INN-alirocumab – Charakterystyka Produktu Leczniczego Web site. https://www.ema.europa.eu/en/documents/product-information/praluent-epar-product-information_pl.pdf. Accessed May 10, 2023.
Repatha, INN-evolocumab – Charakterystyka Produktu Leczniczego Web site. https://www.ema.europa.eu/en/documents/product-information/repatha-epar-product-information_pl.pdf. Accessed May 10, 2023.
Inklisiran dopuszczony do obrotu w UE [Inclisiran authorised in the EU]. Puls Medycyny Web site. https://pulsmedycyny.pl/firma-novartis-uzyskala-pozwolenie-na-dopuszczenie-1109134. Published February 23, 2021. Accessed May 10, 2023.
Raal F, Kallend D, Ray K, et al. Inklisiran for Heterozygous Familial Hypercholesterolemia. N Engl J Med. 2020;382(16):1520–1530. doi: 10.1056/NEJMoa1913805.
Ray K, Wright R, Kallend D, et al. Two Phase 3 Trials of Inklisiran in Patients with Elevated LDL Cholesterol. N Engl J Med. 2020;382(16):1507–1519. doi: 10.1056/NEJMoa1912387.
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