RNA interference in lipid-lowering therapies: The emerging role of Inclisiran in atherosclerotic dyslipidemia management [ARN de interferencia en terapias hipolipemiantes e Inclisirán en el Manejo de la Dislipidemia Aterosclerótica]
DOI:
https://doi.org/10.62574/shpqzd15Keywords:
hypercholesterolemia, small interfering RNA, proprotein convertasesAbstract
Objective: To analyse interference RNA in lipid-lowering therapies and Inclisiran in the management of atherosclerotic dyslipidaemia based on scientific evidence. Method: Qualitative literature review of 30 scientific documents. Results and Conclusion: Nine distinctive characteristics of ageing were identified, classified as primary (genomic instability, telomere shortening, epigenetic alterations, loss of proteostasis), antagonistic (sensory nutrient dysregulation, mitochondrial dysfunction, cellular senescence) and integrative (stem cell depletion, altered intercellular communication). Epigenetic clocks emerge as accurate biomarkers for determining biological age. Cell reprogramming interventions with Yamanaka factors have demonstrated the ability to reverse markers of ageing.
Downloads
References
Ray KK, Landmesser U, Leiter LA, et al. Inclisiran for the treatment of dyslipidemia. Expert Opin Investig Drugs. 2018;27(3):235-43. Disponible en: https://pubmed.ncbi.nlm.nih.gov/29451410/
Ray KK, Wright RS, Kallend D, et al. Two Phase 3 Trials of Inclisiran in Patients with Elevated LDL Cholesterol. N Engl J Med. 2020;382(16):1507-19. doi:10.1056/NEJMoa1912387
Mikhailidis DP, Toth PP, Banach M. Inclisiran in dyslipidemia. Eur Heart J. 2021;42(7):674-82. Disponible en: https://pubmed.ncbi.nlm.nih.gov/34061126/
Ray KK, Wright RS, Kallend D, et al. Inclisiran siRNA technology in the management of dyslipidemia. Expert Opin Biol Ther. 2024;24(2):145-53. Disponible en: https://www.sciencedirect.com/science/article/pii/S0146280624000586
Kallend D, Wright RS, Xu J, et al. Safety and Tolerability of Inclisiran for Treatment of Hyperlipidemia. J Am Coll Cardiol. 2023;81(10):1028-37. Disponible en: https://www.jacc.org/doi/10.1016/j.jacc.2023.10.007
Frampton JE. Inclisiran: A Review in Hypercholesterolemia. Am J Cardiovasc Drugs. 2023;23(2):219-30. doi:10.1007/s40256-023-00568-7
Fragozo-Ramos MC, López-Sendón J, Fernández-Avilés F. Inclisiran, ARN interferente pequeño: un nuevo enfoque para el tratamiento del colesterol LDL elevado. Rev Colomb Cardiol. 2022;29(6):663-72.
Valle-Alfonso J. Inclisiran: una nueva promesa en el tratamiento de la dislipemia. Blog de la Sociedad Española de Cardiología. 2020. Disponible en: https://secardiologia.es/blog/11483-inclisiran-una-nueva-promesa-en-el-tratamiento-de-la-dislipemia
Clark J, Montori V. In patients with ASCVD and elevated LDL-C with maximal statin therapy, inclisiran reduced LDL-C levels at 18 months. Ann Intern Med. 2020;173(4):JC18. doi:10.7326/ACPJ202008180-018
Ray KK, Landmesser U, Leiter LA, et al. Inclisiran for the treatment of hypercholesterolemia: pooled efficacy and safety results from the ORION-9, ORION-10, and ORION-11 trials. Lancet. 2021;398(10304):2388-98.
Kallend D, Colhoun HM, Ginsberg HN, et al. Efficacy and safety of inclisiran in patients with hypercholesterolemia: results from the ORION-9, ORION-10, and ORION-11 trials. Eur Heart J. 2021;42(36):3589-98.
Morrow DA, Braunwald E, Mancia G, et al. Efficacy and safety of inclisiran in patients with hypercholesterolemia: findings from the ORION-11 trial. J Am Coll Cardiol. 2021;77(15):1818-28.
Pavía-López Abel A, Alcocer-Gamba MA, Ruiz-Gastelum ED, Mayorga-Butrón JL, Mehta R, Díaz-Aragón FA, et al. Guía de práctica clínica mexicana para el diagnóstico y tratamiento de las dislipidemias y enfermedad cardiovascular aterosclerótica. Arch Cardiol Méx. 2022;92(Suppl 1):1-62.
Gencer B, et al. Tendencias actuales en el manejo de lípidos. Curr Opin Lipidol. 2021;32(2):84-90.
Tsimikas S, Karwatowska-Prokopczuk E, Aylward PE, et al. Inclisiran for the treatment of hypercholesterolemia: results from the ORION-9 trial. J Am Coll Cardiol. 2020;75(23):2850-9.
Tsimikas S, Baum SJ, Wiviott SD, et al. A randomized trial of inclisiran in patients with elevated cholesterol. N Engl J Med. 2020;382(16):1507-16.
Baum SJ, Tsimikas S, Karwatowska-Prokopczuk E, et al. Safety and efficacy of inclisiran for the treatment of heterozygous familial hypercholesterolemia: results from the ORION-9 trial. Atherosclerosis. 2021;319:8-16.
Parker RA, Stroes E, Toth PP, et al. Inclisiran in patients with cardiovascular disease: efficacy and safety results from the ORION-10 and ORION-11 trials.
Ginsberg HN, Baigent C, Cook NR, et al. Efficacy and safety of inclisiran in patients with elevated cholesterol: pooled analysis from the ORION-9, ORION-10, and ORION-11 trials.
Stein EA, Gipe D, Bruckert E, et al. Long-term safety and tolerability of inclisiran in the ORION-11 trial. J Am Coll Cardiol. 2022;80(4):393-401.
Toth PP, Ginsberg HN, Ray KK, et al. Long-term safety and efficacy of inclisiran in patients with hypercholesterolemia: 3-year follow-up from the ORION-11 trial. J Clin Lipidol. 2023;17(5):456-63.
Bergmark BA, Baum SJ, Karwatowska-Prokopczuk E, et al. The efficacy of inclisiran in patients with atherosclerotic cardiovascular disease and elevated LDL-C: a pooled analysis of ORION-9, ORION-10, and ORION-11. JAMA Cardiol. 2021;6(12):1341-9.
Nishikido T, Ray KK. Inclisiran for the treatment of dyslipidemia. Expert Opin Investig Drugs. 2018;27(3):287-94.
Lamb YN. Inclisiran: First Approval [published correction appears in Drugs. 2021 Jun;81(9):1129]. Drugs. 2021;81(3):389-95. doi:10.1007/s40265-021-01473-6
Wilkinson MJ, Bajaj A, Brousseau ME, Taub PR. Harnessing RNA Interference for Cholesterol Lowering: The Bench-to-Bedside Story of Inclisiran. J Am Heart Assoc. 2024;13(6):e032031. doi:10.1161/JAHA.123.032031
Zhang Y, Chen H, Hong L, et al. Inclisiran: a new generation of lipid-lowering siRNA therapeutic. Front Pharmacol. 2023;14:1260921. doi:10.3389/fphar.2023.1260921
Wright RS, Raal FJ, Koenig W, et al. Inclisiran administration potently and durably lowers LDL-C over an extended-term follow-up: the ORION-8 trial. Cardiovasc Res. 2024;120(12):1400-10. doi:10.1093/cvr/cvae109
Katsiki N, Vrablik M, Banach M, Gouni-Berthold I. Inclisiran, Low-Density Lipoprotein Cholesterol and Lipoprotein (a). Pharmaceuticals (Basel). 2023;16(4):577. doi:10.3390/ph16040577
Ray KK, Troquay RPT, Visseren FLJ, et al. Long-term efficacy and safety of inclisiran in patients with high cardiovascular risk and elevated LDL cholesterol (ORION-3): results from the 4-year open-label extension of the ORION-1 trial. Lancet Diabetes Endocrinol. 2023;11(2):109-19. doi:10.1016/S2213-8587(22)00353-9
Albosta MS, Grant JK, Taub P, Blumenthal RS, Martin SS, Michos ED. Inclisiran: A New Strategy for LDL-C Lowering and Prevention of Atherosclerotic Cardiovascular Disease. Vasc Health Risk Manag. 2023;19:421-31. doi:10.2147/VHRM.S338424
Downloads
Published
Issue
Section
License
Copyright (c) 2025 María Gabriela Balarezo-García, Diego Armando Suárez-Páez, Christian Alexis Ávila-Díaz, Heydi Nicole Paguay-Pingos (Autor/a)
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
CC BY-NC-SA : Esta licencia permite a los reutilizadores distribuir, remezclar, adaptar y construir sobre el material en cualquier medio o formato solo con fines no comerciales, y solo siempre y cuando se dé la atribución al creador. Si remezcla, adapta o construye sobre el material, debe licenciar el material modificado bajo términos idénticos.
