{"id":252967,"date":"2024-12-30T19:28:18","date_gmt":"2024-12-30T18:28:18","guid":{"rendered":"https:\/\/r3i.org\/editoriales-r3i\/editorial-10-20-dirigirse-a-los-trigliceridos-nuevos-agentes-amplian-el-campo\/"},"modified":"2025-02-15T01:17:45","modified_gmt":"2025-02-15T00:17:45","slug":"editorial-10-20-dirigirse-a-los-trigliceridos-nuevos-agentes-amplian-el-campo","status":"publish","type":"page","link":"https:\/\/r3i.org\/es\/editoriales-r3i\/editorial-10-20-dirigirse-a-los-trigliceridos-nuevos-agentes-amplian-el-campo\/","title":{"rendered":"Editorial 10\/20 – Dirigirse a los triglic\u00e9ridos: Nuevos agentes ampl\u00edan el campo"},"content":{"rendered":"

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Editoriales R3i<\/h2>\n

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Octubre 2020<\/span><\/h5>\n
Agentes nuevos que act\u00faan sobre los triglic\u00e9ridos ampl\u00edan el panorama<\/h5>\n
Prof. Jean-Charles Fruchart, Prof. Michel Hermans, Prof. Pierre Amarenco<\/span><\/h6>\n

Durante mucho tiempo los lineamientos han reconocido que los triglic\u00e9ridos (TG) elevados son un marcador del riesgo cardiovascular 1. En efecto, los TG y las lipoprote\u00ednas ricas en TG se encuentran entre los l\u00edpidos y las lipoprote\u00ednas aterog\u00e9nicos que se cree que son tanto factores causales como pron\u00f3sticos de la enfermedad cardiovascular ateroescler\u00f3tica (ASCVD) 2,3. Hasta el momento, no obstante, los grupos de lineamientos proporcionan \u00abniveles deseables de TG\u00bb en lugar de objetivos, debido a los datos definitivos limitados de evidencia de los estudios de resultados cardiovasculares que usan abordajes terap\u00e9uticos convencionales. Los \u00e1cidos grasos omega-3, espec\u00edficamente el \u00e1cido icosapentaenoico (EPA), han logrado aceptaci\u00f3n a la luz de los resultados del estudio de referencia REDUCE-IT (Reducci\u00f3n de Episodios Cardiovasculares con Etilo de Icosapento) 4, con el aval del estudio m\u00e1s antiguo JELIS (estudio de intervenci\u00f3n de l\u00edpidos con \u00e1cido eicosapentaenoico de Jap\u00f3n [EPA]) 5. Los grupos de lineamiento han incorporado ahora los resultados de REDUCE-IT en las recomendaciones actualizadas (6-8). Sin embargo, tambi\u00e9n es evidente que la disminuci\u00f3n de TG por s\u00ed sola no explica los beneficios observados en REDUCE-IT, lo que suscita debates continuos.
Se necesitan abordajes nuevos para el manejo de la hipertrigliceridemia. Los estudios con aleatorizaci\u00f3n mendeliana han sido una herramienta crucial en la b\u00fasqueda de objetivos terap\u00e9uticos nuevos. Los resultados han impulsado desarrollos cl\u00ednicos continuos centrados en dos objetivos prometedores: la apolipoprote\u00edna CIII (ApoCIII) y la prote\u00edna 3 similar a la angiopoyetina (ANGPTL3) (9-11). La apoCIII es una reguladora clave del metabolismo de la lipoprote\u00edna rica en TG debido a su inhibici\u00f3n de la lipoprote\u00edna lipasa y la lipasa hep\u00e1tica, lo que lleva a una disminuci\u00f3n de la reabsorci\u00f3n hep\u00e1tica de lipoprote\u00ednas ricas en TG, adem\u00e1s de una mejora de la s\u00edntesis y secreci\u00f3n de lipoprote\u00ednas de muy baja densidad (VLDL) del h\u00edgado. La ANGPTL3 se expresa exclusivamente en el h\u00edgado e inhibe la hidr\u00f3lisis de TG mediante la inhibici\u00f3n de la funci\u00f3n de la lipoprote\u00edna lipasa. Existen estudios experimentales que tambi\u00e9n proporcionan evidencia de que la ANGPTL3 intracelular tiene otros modos de acci\u00f3n potenciales, incluida la interferencia con la secreci\u00f3n de VLDL, lo que lleva a una reducci\u00f3n de VLDL-TG 12, aunque es necesario que m\u00e1s investigaciones expliquen la funci\u00f3n intracelular de la ANGPTL3 y su efecto en el metabolismo de las lipoprote\u00ednas.<\/p>\n

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Hay varios agentes nuevos que act\u00faan sobre estas dianas terap\u00e9uticas que se encuentran en ensayos en fase 2 y 3. Entre estos se incluyen los oligonucle\u00f3tidos antisentido, los abordajes de silenciamiento g\u00e9nico y los tratamientos con anticuerpos monoclonales. En el congreso virtual de la Sociedad Europea de Cardiolog\u00eda de este a\u00f1o, se presentaron datos de dos agentes nuevos: ARO-ANG3, un peque\u00f1o ARN de interferencia 13,14 y el vupanorsen, un medicamento antisentido conjugado con N-acetilgalactosamina que act\u00faa sobre la ANGPTL3, este \u00faltimo comentado en el enfoque de este mes 15. Ambos presentan una interesante promesa en la b\u00fasqueda de nuevos abordajes terap\u00e9uticos para los TG elevados.<\/p>\n

Por supuesto, el candidato favorito en este campo es el pemafibrato, un modulador de receptores alfa activado por proliferadores peroxisomales (SPPARM\u03b1). Existen pruebas confiables que diferencian a este agente de los fibratos convencionales (agonistas de PPAR\u03b1), en particular en relaci\u00f3n con su perfil de seguridad, dada la ausencia de elevaci\u00f3n de la creatinina en suero, un inconveniente del fenofibrato en la pr\u00e1ctica cl\u00ednica habitual, en particular entre los pacientes con alg\u00fan grado de insuficiencia renal (16, 17). Lo esencial es determinar si la disminuci\u00f3n de los TG con pemafibrato en pacientes de alto riesgo con hipertrigliceridemia tratados con estatinas reduce los episodios cardiovasculares. En tal sentido, esperamos los resultados de PROMINENT 18, que son cruciales para responder las preguntas pendientes relacionadas con el rol de las lipoprote\u00ednas ricas en TG en el riesgo cardiovascular residual.<\/p>\n

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Referencias<\/strong><\/p>\n

    \n
  1. \n
    \u00a0Miller M, Stone NJ, Ballantyne C, et al. Triglycerides and cardiovascular disease: a scientific statement from the American Heart Association. Circulation 2011;123:2292\u20132333.
    2. Ganda OP, Bhatt DL, Mason RP, et al. Unmet need for adjunctive dyslipidemia therapy in hypertriglyderidemia management. J Am Coll Cardiol 2018;72:330\u2013343.
    3. Budoff M. Triglycerides and triglyceride-rich lipoproteins in the causal pathway of cardiovascular disease. Am J Cardiol 2016;118:138\u2013145.
    4. Bhatt DL, Steg PG, Miller M, et al; REDUCE-IT Investigators. Cardiovascular risk reduction with icosapent ethyl for hypertriglyceridemia. N Engl J Med 2019;380:11-22.
    5. Yokoyama M, Origasa H, Matsuzaki M, et al. Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis. Lancet. 2007;369:1090\u20131098.
    6. Mach F, Baigent C Catapano AL, et al. 2019 ESC\/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk: The Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS) Eur Heart J. 2020;41:111\u2013188.
    7. NLA position on the use of icosapent ethyl in high and very-high risk patients. Jacksonville, FL: National Lipid Association, 2019. https:\/\/www.lipid.org\/nla\/nla-position-use-icosapent-ethyl-high-and-very-high-risk-patients<\/a>.
    8. Skulas-Ray AC, Wilson PWF, Harris WS, et al. Omega-3 fatty acids for the management of hypertriglyceridemia: A science advisory from the American Heart Association. Circulation 2019;140:e673\u2013e691.
    9. J\u00f8rgensenAB, Frikke-SchmidtR, NordestgaardBG, et al. Loss-of-function mutations in APOC3 and risk of ischemic vascular disease. N Engl J Med 2014;371:32\u201341.
    10. TG and HDL Working Group of the Exome Sequencing Project NH, Lung, and Blood Institute Loss-of-function mutations in APOC3, triglycerides, and coronary disease. N Engl J Med 2014;371:22\u201331.
    11. Stitziel NO, KheraAV, WangX, et al. ANGPTL3 deficiency and protection against coronary artery disease. J Am Coll Cardiol 2017;69:2054\u20132063.
    12. Wang Y, Gusarova V, BanfiS, et al. Inactivation of ANGPTL3 reduces hepatic VLDL-triglyceride secretion. J Lipid Res 2015;56:1296\u20131307.
    13. Ballantyne C. RNA interference targeting apolipoprotein C-III with ARO-APOC3 in healthy volunteers mimics lipid and lipoprotein findings seen in subjects with inherited apolipoprotein C-III deficiency. ESC Congress Virtual Meeting 2020.
    14. Watts G. RNAi inhibition of angiopoietin-like protein 3 (ANGPTL3) with ARO-ANG3 mimics the lipid and lipoprotein profile of familial combined hypolipidemia. ESC Congress Virtual Meeting 2020.
    15. Gaudet D, Karwatowska-Prokopczuk E, Baum SJ et al. Vupanorsen, an N-acetyl galactosamine-conjugated antisense drug to ANGPTL3 mRNA, lowers triglycerides and atherogenic lipoproteins in patients with diabetes, hepatic steatosis, and hypertriglyceridaemia. Eur Heart J 2020; doi:10.1093\/eurheartj\/ehaa689
    16. Yamashita S, Masuda D, Matsuzawa Y. Pemafibrate, a new selective PPAR\u03b1 Modulator: drug concept and its clinical applications for dyslipidemia and metabolic diseases. Curr Atheroscler Rep 2020;221:5.
    17. Fruchart JC, Hermans MP, Fruchart-Najib J. Selective Peroxisome Proliferator-Activated Receptor Alpha Modulators (SPPARM\u03b1): new opportunities to reduce residual cardiovascular risk in chronic kidney disease? Curr Atheroscler Rep 2020;228:43.
    18. Pemafibrate to reduce cardiovascular outcomes by reducing triglycerides in patients with diabetes (PROMINENT) [NCT03071692]     https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03071692<\/a><\/div>\n
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    Editoriales R3iOctubre 2020 Agentes nuevos que act\u00faan sobre los triglic\u00e9ridos ampl\u00edan el panorama Prof. Jean-Charles Fruchart, Prof. Michel Hermans, Prof. Pierre Amarenco Durante mucho tiempo los lineamientos han reconocido que los triglic\u00e9ridos (TG) elevados son un marcador del riesgo cardiovascular 1. En efecto, los TG y las lipoprote\u00ednas ricas en TG se encuentran entre los […]<\/p>\n","protected":false},"author":258497324,"featured_media":0,"parent":252805,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":{"_et_pb_use_builder":"on","_et_pb_old_content":"","_et_gb_content_width":"","_crdt_document":"","jetpack_post_was_ever_published":false,"footnotes":""},"class_list":["post-252967","page","type-page","status-publish","hentry"],"yoast_head":"\nEditorial 10\/20 - Dirigirse a los triglic\u00e9ridos: Nuevos agentes ampl\u00edan el campo - R3I<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/r3i.org\/es\/editoriales-r3i\/editorial-10-20-dirigirse-a-los-trigliceridos-nuevos-agentes-amplian-el-campo\/\" \/>\n<meta property=\"og:locale\" content=\"es_ES\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Editorial 10\/20 - Dirigirse a los triglic\u00e9ridos: Nuevos agentes ampl\u00edan el campo - R3I\" \/>\n<meta property=\"og:description\" content=\"Editoriales R3iOctubre 2020 Agentes nuevos que act\u00faan sobre los triglic\u00e9ridos ampl\u00edan el panorama Prof. Jean-Charles Fruchart, Prof. Michel Hermans, Prof. Pierre Amarenco Durante mucho tiempo los lineamientos han reconocido que los triglic\u00e9ridos (TG) elevados son un marcador del riesgo cardiovascular 1. 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