Inhibición de PCSK9: una nueva alternativa para reducir el colesterol y prevenir la enfermedad cardiovascular aterosclerosa

Gabriela Alexandra Solano Peña; Gabriela Fernanda Acurio Armas; Gabriela Alejandra Díaz Teran; Susana Patricia Palacios Serrano; Andrea Carolina Cobo Reyes; Daniel Albino Pullas Taboada; Gissel Katherine Carvajal Chango

doi:10.56294/saludcyt2023587

Autores/as

Gabriela Alexandra Solano Peña Solca Núcleo Tungurahua, Ecuador. https://orcid.org/0009-0005-3579-9566
Gabriela Fernanda Acurio Armas Médico Investigador Independiente, Ecuador. https://orcid.org/0009-0002-3961-2541
Gabriela Alejandra Díaz Teran Hospital General de Latacunga, Ecuador. https://orcid.org/0000-0003-4555-1554
Susana Patricia Palacios Serrano Hospital Regional Docente Ambato, Ecuador. https://orcid.org/0000-0002-8994-6155
Andrea Carolina Cobo Reyes Hospital Básico Salcedo, Ecuador. https://orcid.org/0000-0003-3209-8543
Daniel Albino Pullas Taboada Médico Investigador Independiente, Ecuador. https://orcid.org/0009-0000-2167-0626
Gissel Katherine Carvajal Chango Hospital Regional Docente Ambato, Ecuador. https://orcid.org/0009-0008-8881-1372

DOI:

https://doi.org/10.56294/saludcyt2023587

Palabras clave:

PCSK9, Inhibidores de PCSK9, Colesterol LDL, Enfermedad cardiovascular aterosclerótica, Terapia antilipidémica

Resumen

Introducción: La enfermedad cardiovascular aterosclerótica es la principal causa de mortalidad y morbilidad a nivel mundial. Uno de los factores clave en su desarrollo es el colesterol LDL elevado. La proproteína convertasa subtilisina/kexina tipo 9 (PCSK9) es una molécula que regula los niveles de colesterol LDL.
Objetivo: El propósito de esta revisión es proporcionar un análisis exhaustivo de la evidencia en torno a la inhibición de PCSK9 como una terapia efectiva para reducir el colesterol y prevenir la enfermedad cardiovascular aterosclerótica.
Metodología: Se realizó una revisión bibliográfica exhaustiva utilizando bases de datos médicas, incluyendo PubMed, Embase y Cochrane Library. Los términos de búsqueda incluyeron "PCSK9", "inhibidores de PCSK9", "colesterol", "LDL" y "enfermedad cardiovascular aterosclerótica".
Resultados: La evidencia sugiere que los inhibidores de PCSK9 son efectivos para reducir los niveles de colesterol LDL en pacientes con hipercolesterolemia. Varios ensayos clínicos han demostrado que estos fármacos pueden reducir el colesterol LDL hasta en un 60% en comparación con el placebo. Además, los inhibidores de PCSK9 parecen tener un perfil de seguridad favorable y son bien tolerados por la mayoría de los pacientes. Varios estudios también han demostrado que los inhibidores de PCSK9 pueden reducir el riesgo de eventos cardiovasculares en pacientes con enfermedad aterosclerótica preexistente.
Conclusión: Los inhibidores de PCSK9 representan una estrategia terapéutica prometedora para el control del colesterol LDL y la prevención de la enfermedad cardiovascular aterosclerótica. Los estudios futuros deben centrarse en determinar el efecto a largo plazo de estos fármacos en la morbimortalidad cardiovascular y en explorar formas de mejorar el acceso y la asequibilidad a estas terapias.

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Chapman MJ, Stock JK, Ginsberg HN. PCSK9 inhibitors and cardiovascular disease: heralding a new therapeutic era. Curr Opin Lipidol. 2015 Dec;26(6):511. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4927326/

Gallego-Colon E, Daum A, Yosefy C. Statins and PCSK9 inhibitors: A new lipid-lowering therapy. Eur J Pharmacol. 2020 Aug 5;878:173114. Available from: https://www.sciencedirect.com/science/article/abs/pii/S0014299920302065

Lusis AJ. Atherosclerosis. Nature. 2000 Sep 14;407(6801):233-41.

Herrington W, Lacey B, Sherliker P, Armitage J, Lewington S. Epidemiology of atherosclerosis and the potential to reduce the global burden of atherothrombotic disease. Circ Res. 2016 Feb 19;118(4):535-46.

Organización Mundial de la Salud. Las enfermedades cardiovasculares (ECV). [Internet]. 2017 [cited 2023 Oct 12]. Available from: https://www.who.int/es/news-room/fact-sheets/detail/cardiovascular-diseases-(cvds)

Organización Panamericana de la Salud. Enfermedades cardiovasculares. [Internet]. 2020 [cited 2023 Oct 12]. Available from: https://www.paho.org/es/temas/enfermedades-cardiovasculares

Instituto Nacional de Estadística y Censos. Anuario de estadísticas de salud, mortalidad. [Internet]. 2017 [cited 2023 Oct 12]. Available from: https://www.indec.gob.ar/ftp/cuadros/sociedad/anuario_salud_mortalidad_2017.pdf

Della Badia LA, Elshourbagy NA, Mousa SA. Targeting PCSK9 as a promising new mechanism for lowering low-density lipoprotein cholesterol. Pharmacol Ther. 2016 Dec;164:183-94. Available from: https://www.sciencedirect.com/science/article/abs/pii/S0163725816300572

Fihn SD, Blankenship JC, Alexander KP, Bittl JA, Byrne JG, Fletcher BJ, et al. ACC/AHA/AATS/PCNA/SCAI/STS focused update of the guideline for the diagnosis and management of patients with stable ischemic heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines, and the American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. J Am Coll Cardiol. 2012 Dec 18;60(24):645-81.

Sabatine MS, Giugliano RP, Keech AC, Honarpour N, Wiviott SD, Murphy SA, et al. Evolocumab and clinical outcomes in patients with cardiovascular disease. N Engl J Med. 2017 May 4;376(18):1713-22.

Delialis D, Dimopoulou MA, Papaioannou M, Kotsira G, Maneta E, Mavraganis G, et al. Pcsk9 inhibition in Atherosclerotic cardiovascular disease. Curr Pharm Des. 2023;29(23):1-1.

Adorni MP, Zimetti F, Lupo MG, Ruscica M, Ferri N. Naturally occurring PCSK9 inhibitors. Nutrients. 2020;12(5):1440.

Päth G, Perakakis N, Mantzoros CS, Seufert J. PCSK9 inhibition and cholesterol homeostasis in insulin producing β-cells. Lipids Health Dis. 2022;21(1):138.

Beltran RA, Zemeir KJ, Kimberling CR, Kneer MS, Mifflin MD, Broderick TL. Is a PCSK9 Inhibitor Right for Your Patient? A Review of Treatment Data for Individualized Therapy. Int J Environ Res Public Health. 2022;19(24):16899.

Grundy SM, Stone NJ, Bailey AL, Beam C, Birtcher KK, Blumenthal RS, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2019;73(24):e285-e350.

Montano M de las NV, Martínez M de la CG, Lemus LP. Rehabilitation of occupational stress from the perspective of Health Education. Community and Interculturality in Dialogue 2023;3:71–71. https://doi.org/10.56294/cid202371.

Robinson JG, Farnier M, Krempf M, Bergeron J, Luc G, Averna M, et al. Efficacy and safety of alirocumab in reducing lipids and cardiovascular events. N Engl J Med. 2015;372(16):1489-1499.

Nissen SE, Stroes E, Dent-Acosta RE, Rosenson RS, Lehman SJ, Sattar N, et al. Efficacy and tolerability of evolocumab vs ezetimibe in patients with muscle-related statin intolerance: the GAUSS-3 randomized clinical trial. JAMA. 2016;315(15):1580-1590.

Bernelot Moens SJ, Neele AE, Kroon J, van der Valk FM, Van den Bossche J, Hoeksema MA, et al. PCSK9 monoclonal antibodies reverse the pro-inflammatory profile of monocytes in familial hypercholesterolaemia. Eur Heart J. 2017;38(20):1584-1593.

Wong ND, Young D, Zhao Y, Nguyen H, Caballes J, Khan I, et al. Prevalence of the American College of Cardiology/American Heart Association statin eligibility groups, statin use, and low-density lipoprotein cholesterol control in US adults using the National Health and Nutrition Examination Survey 2011-2012. J Clin Lipidol. 2020;10(5):1109-1118.

Rasmussen, K. L. (2016). Plasma levels of apolipoprotein E, APOE genotype and risk of dementia and ischemic heart disease: A review. Atherosclerosis, 255, 145-155.

Tian, Z., Liu, Y., Zhang, H., Zhang, Y., Liu, W., Li, L., Liu, J., & Shi, Y. (2016). Inhibition of PCSK9 potentiates immune checkpoint therapy for cancer. Nature, 588(7838), 693-698.

Zhou, Q., & Liao, J. K. (2020). PCSK9 and atherosclerosis: looking beyond LDL. The Lancet, 396(10260), 1441-1443.

Seidah, N. G. (2016). PCSK9 as a therapeutic target of dyslipidemia. Expert opinion on therapeutic targets, 13(1), 19-28.

Steffens, D., Bramlage, P., Scheeff, C., Kasner, M., Hassanein, A., Friebel, J., & Rauch-Kröhnert, U. (2020). PCSK9 inhibitors and cardiovascular outcomes. Expert opinion on biological therapy, 20(1), 35-47.

Reiner, Ž. (2015). PCSK9 inhibitors–past, present and future. Expert Opinion on Drug Metabolism & Toxicology, 11(10), 1517-1521.

Gencer, B., Lambert, G., & Mach, F. (2015). PCSK9 inhibitors. Swiss Medical Weekly, 145(1516), w14094-w14094.

Chaudhary, R., Garg, J., Shah, N., & Sumner, A. (2017). PCSK9 inhibitors: a new era of lipid lowering therapy. World journal of cardiology, 9(2), 76.

Urban, D., Pöss, J., Böhm, M., & Laufs, U. (2013). Targeting the proprotein convertase subtilisin/kexin type 9 for the treatment of dyslipidemia and atherosclerosis. Journal of the American College of Cardiology, 62(16), 1401-1408.

Raal, F. J., Honarpour, N., Blom, D. J., Hovingh, G. K., Xu, F., Scott, R., Wasserman, S. M., & Stein, E. A. (2015). Inhibition of PCSK9 with evolocumab in homozygous familial hypercholesterolaemia (TESLA Part B): a randomised, double-blind, placebo-controlled trial. The Lancet, 385(9965), 341-350.

Téllez FC, Gimenez M, González C. Education for the control of arterial hypertension in older adults: An effective approach. Community and Interculturality in Dialogue 2021;1:3–3. https://doi.org/10.56294/cid20213.

Tian Y, Yang B, Qiu W, Hao Y, Zhang Z, Yang B, et al. PCSK9 regulates apoptosis in human neuroglioma U251 cells via mitochondrial signaling pathways. Int J Clin Exp Pathol. 2016;9(6):6606-14.

Liu C, Chen J, Chen H, Zhang T, He D, Luo Q, et al. PCSK9 inhibition: from current advances to evolving future. Cells. 2022;11(19):2972. Available from: https://www.mdpi.com/2073-4409/11/19/2972

Cannon CP, Cariou B, Blom D, McKenney JM, Lorenzato C, Pordy R, et al. Efficacy and safety of alirocumab in high cardiovascular risk patients with inadequately controlled hypercholesterolaemia on maximally tolerated doses of statins: the ODYSSEY COMBO II randomized controlled trial. Eur Heart J. 2015;36(19):1186-94.

Farnier M, Jones P, Severance R, Averna M, Steinhagen-Thiessen E, Colhoun H, et al. Efficacy and safety of adding alirocumab to rosuvastatin versus adding ezetimibe or doubling the rosuvastatin dose in high cardiovascular-risk patients: The ODYSSEY OPTIONS II randomized trial. Atherosclerosis. 2016;244:138-46.

Kazi DS, Moran AE, Coxson PG, Penko J, Ollendorf DA, Pearson SD, et al. Cost-effectiveness of PCSK9 inhibitor therapy in patients with heterozygous familial hypercholesterolemia or atherosclerotic cardiovascular disease. JAMA. 2016;316(7):743-53.

Kastelein JJ, Ginsberg HN, Langslet G, Hovingh GK, Ceska R, Dufour R, et al. ODYSSEY FH I and FH II: 78 week results with alirocumab treatment in 735 patients with heterozygous familial hypercholesterolaemia. Eur Heart J. 2015;36(43):2996-3003.

Ridker PM, Revkin J, Amarenco P, Brunell R, Curto M, Civeira F, et al. Cardiovascular efficacy and safety of bococizumab in high-risk patients. N Engl J Med. 2017;376(16):1527-39.

Ballantyne CM, Neutel J, Cropp A, Duggan W, Wang EQ, Plowchalk D, et al. Safety and efficacy of bococizumab (RN316/PF-04950615), a monoclonal antibody that inhibits proprotein convertase subtilisin/kexin type 9, in hypercholesterolaemic patients. Eur Heart J. 2015;36(29):1957-65.

Stein EA, Honarpour N, Wasserman SM, Xu F, Scott R, Raal FJ. Effect of the proprotein convertase subtilisin/kexin 9 monoclonal antibody, AMG 145, in homozygous familial hypercholesterolemia. Circulation. 2013;128(19):2113-20.