Palabras clave
Farmacología
Interferencia de ARN
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Resumen
Objetivo: Analizar el mecanismo de acción, eficacia, seguridade, los principales estudios sobre el inclisirán en el tratamiento de la hipercolesterolemia. Revisión bibliográfica: Hipercolesterolemia es uno de los trastornos metabólicos más prevalentes en el mundo. Aunque las estatinas son los fármacos de elección para el tratamiento enfocado en la reducción del colesterol LDL (LDL-C), pueden no ser toleradas o resultar insuficientes en hasta el 20% de los pacientes. Los medicamentos dirigidos a la proproteína convertasa subtilisina/kexina tipo 9 (PCSK9) han surgido como opciones terapéuticas prometedoras. El inclisirán se une a los receptores de asialoglicoproteína (ASGPR), expresados únicamente en los hepatocitos, lo que explica su perfil de seguridad; participa en un complejo ribonucleoproteico (RISC); induce el silenciamiento del ARN mensajero (ARNm); reduce la síntesis de PCSK9; aumenta el número de receptores de LDL en la superficie de los hepatócitos, disminuye la concentración sérica de LDL-C. Consideraciones finales: El inclisirán es una molécula de interferencia génica que inhibe la síntesis de PCSK9, promueve la degradación del ARNm o inhibe su traducción, logrando una reducción robusta, sostenida y con baja variabilidad interindividual del LDL-C. Podría desempeñar un papel importante en la terapia de dislipidemias en el futuro. Es necesario considerar el costo para hacer viable esta propuesta terapéutica para un amplio espectro de pacientes.
Referencias
ALSHAER W, et al. siRNA: Mechanism of action, challenges, and therapeutic approaches. European Journal of Pharmacology, 2021; 905: 174178.
BALLANTYNE CM, et al. Role of Bempedoic Acid in Clinical Practice. Cardiovascular Drugs and Therapy, 2021; 35(4): 10557-21-7147-5.
BANACH M, et al. Personalized management of dyslipidemias in patients with diabetes-it is time for a new approach (2022). Cardiovascular Diabetology, 2022; 21(1): 12933-22-1684-5.
BANACH M, et al. PoLA/CFPiP/PCS/PSLD/PSD/PSH guidelines on diagnosis and therapy of lipid disorders in Poland 2021. Archives of Medical Science, 2021; 17(6): 141941.
BANACH M, et al. Which patients at risk of cardiovascular disease might benefit the most from inclisiran? Polish experts’ opinion. The compromise between EBM and possibilities in healthcare. Archives of Medical Science: AMS, 2022; 18(3): 147435.
BANERJEE Y, et al. Inclisiran: a small interfering RNA strategy targeting PCSK9 to treat hypercholesterolemia. Expert Opinion on Drug Safety, 2022; 21(1): 14740338-1988568.
DEC A, et al. Inclisiran-A Revolutionary Addition to a Cholesterol-Lowering Therapy. International Journal of Molecular Sciences, 2023; 24(7): 24076858.
DYRBUŚ K, et al. Inclisiran-New hope in the management of lipid disorders? Journal of Clinical Lipidology, 2020; 14(1): 111.
FALUDI AA, et al. Atualização da Diretriz Brasileira de Dislipidemias e Prevenção da Aterosclerose – 2017. Arquivos Brasileiros De Cardiologia, 2017; 109(2-1): 20170121.
FITZGERALD K, et al. A Highly Durable RNAi Therapeutic Inhibitor of PCSK9. The New England Journal of Medicine, 2017; 376(1): 1609243.
GIRARDI JM e DO COUTO AA. Role of bempedoic acid in patients with hypercholesterolemia and statin intolerance. Journal Archives of Health, 2023; 4(1): 1-011.
HOVINGH GK, et al. Inclisiran Durably Lowers Low-Density Lipoprotein Cholesterol and Proprotein Convertase Subtilisin/Kexin Type 9 Expression in Homozygous Familial Hypercholesterolemia: The ORION-2 Pilot Study. Circulation, 2020; 141(22): 119-44431.
JABARPOUR M, et al. Protection of renal damage by HMG-CoA inhibitors: A comparative study between atorvastatin and rosuvastatin. Iranian Journal of Basic Medical Sciences, 2020; 23(2): 38239-9080.
KADDOURA R, et al. Efficacy and safety of PCSK9 monoclonal antibodies: an evidence-based review and update. Journal of Drug Assessment, 2020; 9(1): 21556660-1801452.
KHVOROVA A. Oligonucleotide Therapeutics - A New Class of Cholesterol-Lowering Drugs. The New England Journal of Medicine, 2017; 376(1): 1614154.
LI J, et al. Effectiveness and safety of Inclisiran in hyperlipidemia treatment: An overview of systematic reviews. Medicine, 2023; 102(3): 32728.
LUO M, et al. Efficacy and safety of inclisiran in stroke or cerebrovascular disease prevention: a systematic review and meta-analysis of randomized controlled trials. Frontiers in Pharmacology, 2023; 14: 1158274.
NISHIKIDO T. Clinical potential of inclisiran for patients with a high risk of atherosclerotic cardiovascular disease. Cardiovascular Diabetology, 2023; 22(1): 12933-23-1752-4.
RAAL FJ, et al. Inclisiran for the Treatment of Heterozygous Familial Hypercholesterolemia. The New England Journal of Medicine, 2020; 382(16): 1913805.
RAY KK, et al. Effect of an siRNA Therapeutic Targeting PCSK9 on Atherogenic Lipoproteins: Prespecified Secondary End Points in ORION 1. Circulation, 2018; 138(13): 118-34710.
RAY KK, et al. Inclisiran in Patients at High Cardiovascular Risk with Elevated LDL Cholesterol. The New England Journal of Medicine, 2017; 376(15): 1615758.
RAY KK, 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. The Lancet. Diabetes & Endocrinology, 2023; 11(2): 2213-858722353-9.
RAY KK, et al. Two Phase 3 Trials of Inclisiran in Patients with Elevated LDL Cholesterol. The New England Journal of Medicine, 2020; 382(16): 1912387.
REIJMAN MD, et al. Rationale and design of two trials assessing the efficacy, safety, and tolerability of inclisiran in adolescents with homozygous and heterozygous familial hypercholesterolaemia. European Journal of Preventive Cardiology, 2022; 29(9): 25.
RUSCICA M, et al. Lipid Lowering Drugs: Present Status and Future Developments. Current Atherosclerosis Reports, 2021; 23(5): 11883-21-918-3.
SMITH KW e WHITE CM. Inclisiran: A Novel Small Interfering RNA Drug for Low-Density Lipoprotein Reduction. Journal of Clinical Pharmacology, 2022; 62(9): 2045.
SOPPERT J, et al. Lipoproteins and lipids in cardiovascular disease: from mechanistic insights to therapeutic targeting. Advanced Drug Delivery Reviews, 2020; 159: 7.19.
STOEKENBROEK RM, et al. Inclisiran for the treatment of cardiovascular disease: the ORION clinical development program. Future Cardiology, 2018; 14(6): 2018-67.
TOTH PP, et al. Management of Statin Intolerance in 2018: Still More Questions Than Answers. American Journal of Cardiovascular Drugs: Drugs, Devices, and Other Interventions, 2018; 18(3): 40256-17-259-7.
TRABER GM e YU AM. The Growing Class of Novel RNAi Therapeutics. Molecular Pharmacology, 2024; 106(1): 124. 895.
UGOVŠEK S, et al. Influence of lipid-lowering drugs on inflammation: what is yet to be done? Archives of medical science: AMS, 2022; 18(4): 133936.
VIRANI SS, et al. 2023 AHA/ACC/ACCP/ASPC/NLA/PCNA Guideline for the Management of Patients with Chronic Coronary Disease: A Report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines. Circulation, 2023; 148: (9): 1168.
VISSEREN FLJ, et al. 2021 ESC Guidelines on cardiovascular disease prevention in clinical practice. European Heart Journal, 2021; 42(34): 484.