Inclisiran and cardiovascular events: a comprehensive review of efficacy, safety, and future perspectives.
Journal
Current opinion in cardiology
ISSN: 1531-7080
Titre abrégé: Curr Opin Cardiol
Pays: United States
ID NLM: 8608087
Informations de publication
Date de publication:
01 11 2023
01 11 2023
Historique:
medline:
5
10
2023
pubmed:
31
7
2023
entrez:
31
7
2023
Statut:
ppublish
Résumé
This review aims to offer an up-to-date evaluation of Inclisiran's (a small interfering RNA treatment) ability to decrease low-density lipoprotein cholesterol (LDL-C), as well as its safety and potential effects on decreasing cardiovascular risk. Inclisiran significantly lowers LDL-C levels, as shown by phase III studies, by inhibiting hepatic synthesis of proprotein convertase subtilisin kexin 9 (PCSK-9), a protein implicated in the degradation of LDL receptors. Inclisiran has the benefit of subcutaneous injection twice a year, which may reduce patient nonadherence when compared with other LDL-C reducing therapies such as statins and ezetimibe, which require daily dosing. When added on top of statins, a greater proportion of patients achieved recommended cholesterol goals. It has also demonstrated a good safety profile with few adverse effects. Inclisiran is a promising treatment for lowering LDL-C levels in people at high risk of atherosclerotic cardiovascular disease. It is a practical and well tolerated option for those who struggle to stick to medication regimes because of its twice-yearly dosage schedule and a good safety profile. Although it has been demonstrated to be effective in decreasing LDL-C, further research is needed to determine its impact on reducing cardiovascular events. Nonetheless, Inclisiran is a significant advancement in lipid-lowering medication and could improve patient outcomes.
Identifiants
pubmed: 37522763
doi: 10.1097/HCO.0000000000001074
pii: 00001573-990000000-00087
doi:
Substances chimiques
Cholesterol, LDL
0
Hydroxymethylglutaryl-CoA Reductase Inhibitors
0
ALN-PCS
0
Cholesterol
97C5T2UQ7J
RNA, Small Interfering
0
Proprotein Convertase 9
EC 3.4.21.-
Anticholesteremic Agents
0
Types de publication
Review
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
527-532Informations de copyright
Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.
Références
Arnett DK, Blumenthal RS, Albert MA, et al. 2019 ACC/AHA guideline on the primary prevention of cardiovascular disease: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation 2019; 140:e563–e595.
Gupta M, Blumenthal C, Chatterjee S, et al. Novel emerging therapies in atherosclerosis targeting lipid metabolism. Expert Opin Invest Drugs 2020; 29:611–622.
Lopez-Jimenez F, Almahmeed W, Bays H, et al. Obesity and cardiovascular disease: mechanistic insights and management strategies. A joint position paper by the World Heart Federation and World Obesity Federation. Eur J Prev Cardiol 2022; 29:2218–2237.
Ikezaki H, Lim E, Cupples LA, et al. Small dense low-density lipoprotein cholesterol is the most atherogenic lipoprotein parameter in the prospective Framingham Offspring Study. J Am Heart Assoc 2021; 10:e019140.
Nanna MG, Navar AM, Wojdyla D, et al. The association between low-density lipoprotein cholesterol and incident atherosclerotic cardiovascular disease in older adults: results from the national institutes of health pooled cohorts. J Am Geriatr Soc 2019; 67:2560–2567.
Rosenson RS, Hegele RA. Koenig W: cholesterol-lowering agents: PCSK9 inhibitors today and tomorrow. Circ Res 2019; 124:364–385.
Ray KK, Ference BA, Séverin T, et al. World Heart Federation Cholesterol Roadmap 2022. Glob Heart 2022; 17:75.
Morita SY. Metabolism and modification of apolipoprotein B-containing lipoproteins involved in dyslipidemia and atherosclerosis. Biol Pharm Bull 2016; 39:1–24.
Carr SS, Hooper AJ, Sullivan DR, et al. Non-HDL-cholesterol and apolipoprotein B compared with LDL-cholesterol in atherosclerotic cardiovascular disease risk assessment. Pathology 2019; 51:148–154.
Olofsson SO, Boren J. Apolipoprotein B: a clinically important apolipoprotein which assembles atherogenic lipoproteins and promotes the development of atherosclerosis. J Intern Med 2005; 258:395–410.
Ross S, D’Mello M, Anand SS, et al. Effect of bile acid sequestrants on the risk of cardiovascular events: a mendelian randomization analysis. Circ Cardiovasc Genet 2015; 8:618–627.
Zhang B, Kuipers F, de Boer JF, et al. Modulation of bile acid metabolism to improve plasma lipid and lipoprotein profiles. J Clin Med 2022; 11:4.
Bochem A, Kuivenhoven J, Stroes E. The promise of cholesteryl ester transfer protein (CETP) inhibition in the treatment of cardiovascular disease. Curr Pharm Design 2013; 19:3143–3149.
Silverman MG, Ference BA, Im K, et al. Association between lowering LDL-C and cardiovascular risk reduction among different therapeutic interventions: a systematic review and meta-analysis. JAMA 2016; 316:1289–1297.
Viccica G, Vignali E, Marcocci C. Role of the cholesterol biosynthetic pathway in osteoblastic differentiation. J Endocrinol Invest 2007; 30: (6 Suppl): 8–12.
Stancu C, Sima A. Statins: mechanism of action and effects. J Cell Mol Med 2001; 5:378–387.
Turner T, Stein EA. Nonstatin treatments for managing LDL cholesterol and their outcomes. Clin Ther 2015; 37:2751–2769.
Rossi M, Fabris E, Barbisan D, et al. Lipid-lowering drug therapy: critical approach for implementation in clinical practice. Am J Cardiovasc Drugs 2022; 22:1–15.
Gragnano F, Calabro P. Role of dual lipid-lowering therapy in coronary atherosclerosis regression: evidence from recent studies. Atherosclerosis 2018; 269:219–228.
Schwartz GG, Bessac L, Berdan LG, et al. Effect of alirocumab, a monoclonal antibody to PCSK9, on long-term cardiovascular outcomes following acute coronary syndromes: rationale and design of the ODYSSEY outcomes trial. Am Heart J 2014; 168:682–689. e681.
Gareri C, Polimeni A, Giordano S, et al. Antisense oligonucleotides and small interfering RNA for the treatment of dyslipidemias. J Clin Med 2022; 11:3884.
Ickenstein LM, Garidel P. Lipid-based nanoparticle formulations for small molecules and RNA drugs. Expert Opin Drug Deliv 2019; 16:1205–1226.
Landmesser U, Poller W, Tsimikas S, et al. From traditional pharmacological towards nucleic acid-based therapies for cardiovascular diseases. Eur Heart J 2020; 41:3884–3899.
Do RQ, Vogel RA, Schwartz GG. PCSK9 Inhibitors: potential in cardiovascular therapeutics. Curr Cardiol Rep 2013; 15:1–12.
Tavori H, Fan D, Blakemore JL, et al. Serum proprotein convertase subtilisin/kexin type 9 and cell surface low-density lipoprotein receptor: evidence for a reciprocal regulation. Circulation 2013; 127:2403–2413.
Sniderman A, Thanassoulis G, Couture P, et al. Is lower and lower better and better? A re-evaluation of the evidence from the Cholesterol Treatment Trialists’ Collaboration meta-analysis for low-density lipoprotein lowering. Current Atherosclerosis Reports 2012; 14:303–309.
Wong ND, Shapiro MD. Interpreting the findings from the recent PCSK9 monoclonal antibody cardiovascular outcomes trials. Fron Cardiovasc Med 2019; 6:14.
Douglas G, Channon KM. The pathogenesis of atherosclerosis. Medicine 2014; 42:480–484.
Ference BA, Ginsberg HN, Graham I, et al. Low-density lipoproteins cause atherosclerotic cardiovascular disease. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the European Atherosclerosis Society Consensus Panel. Eur Heart J 2017; 38:2459–2472.
Warden BA, Duell PB. Inclisiran: a novel agent for lowering apolipoprotein B–containing lipoproteins. J Cardiovasc Pharmacol 2021; 78:e157–e174.
Ebenezer O, Comoglio P, Wong GK-S, Tuszynski JA. Development of novel siRNA therapeutics: a review with a focus on Inclisiran for the treatment of hypercholesterolemia. Int J Mol Sci 2023; 24:4019.
Cui H, Zhu X, Li S, et al. Liver-targeted delivery of oligonucleotides with N-acetylgalactosamine conjugation. ACS Omega 2021; 6:16259–16265.
Brandts J, Ray KK. Novel and future lipid-modulating therapies for the prevention of cardiovascular disease. Nat Rev Cardiol 2023; 20:1–17.
Katzmann JL, Packard CJ, Chapman MJ, et al. Targeting RNA with antisense oligonucleotides and small interfering RNA in dyslipidemias: JACC state-of-the-art review. J Am Coll Cardiol 2020; 76:563–579.
Ray KK, Raal FJ, Kallend DG, et al. Inclisiran and cardiovascular events: a patient-level analysis of phase III trials. Eur Heart J 2023; 44:129–138.
Vallejo-Vaz AJ, Bray S, Villa G, et al. Implications of ACC/AHA versus ESC/EAS LDL-C recommendations for residual risk reduction in ASCVD: a simulation study from DA VINCI. Cardiovasc Drugs Ther 2022; 22:1–13.
Serban M-C, Banach M, Mikhailidis DP. Clinical implications of the IMPROVE-IT trial in the light of current and future lipid-lowering treatment options. Expert Opin Pharmacother 2016; 17:369–380.
Brandts J, Ray KK. Clinical implications and outcomes of the ORION Phase III trials. Future Cardiol 2020; 17:769–777.
Stoekenbroek RM, Kallend D, Wijngaard PL, Kastelein JJ. Inclisiran for the treatment of cardiovascular disease: the ORION clinical development program. Future Cardiol 2018; 14:433–442.
Scicchitano P, Milo M, Mallamaci R, et al. Inclisiran in lipid management: a literature overview and future perspectives. Biomed Pharmacother 2021; 143:112227.
Koenig W, Conde LG, Landmesser U, et al. Efficacy and safety of inclisiran in patients with polyvascular disease: pooled, post hoc analysis of the ORION-9, ORION-10, and ORION-11 Phase 3 randomized controlled trials. Cardiovasc Drugs Ther 2022; 22:1–11.
Dixon DL, Pamulapati LG, Bucheit JD, et al. Recent updates on the use of PCSK9 inhibitors in patients with atherosclerotic cardiovascular disease. Curr Atheroscler Rep 2019; 21:16.
DePhillips C. The role of RNA interference therapeutics in hypercholesterolemia and implications for practice. J Nurse Practition 2023; 19:104619.