medsovetМедицинский СоветMeditsinskiy sovet = Medical Council2079-701X2658-5790REMEDIUM GROUP Ltd.10.21518/ms2023-268medsovet-7786Research ArticleДИСЛИПИДЕМИЯDISLIPIDEMIAИзменение представлений о роли комбинированной терапии статином и фибратом у пациентов с гипертриглицеридемиейChanging perceptions about the role of combination therapy with statin and fibrate in patients with hypertriglyceridemiahttps://orcid.org/0000-0002-8505-1848ГиляревскийС. Р.GilyarevskiyS. R.

Гиляревский Сергей Руджерович - доктор медицинских наук, профессор, руководитель кардиологического центра Российского геронтологического научноклинического центра, РНИМУ имени Н.И. Пирогова; профессор кафедры клинической фармакологии и терапии, РМАНПО; Researcher ID: AAN-4179-2021.

129226, Москва, ул. 1-я Леонова, д. 16; 125993, Москва, ул. Баррикадная, д. 2/1, стр. 1

Sergey R. Gilyarevskiy - Dr. Sci. (Med.), Professor, Head of the Cardiology Center of the Russian Gerontological Research and Clinical Center, Pirogov RNRMU; Professor, Department of Clinical Pharmacology and Therapy, RMACPE; Researcher ID: AAN-4179-2021.

16, 1st Leonov St., Moscow, 129226; 2/1, Bldg. 1, Barrikadnaya St., Moscow, 125993

sgilarevsky@rambler.ruРоссийский национальный исследовательский медицинский университет имени Н.И. Пирогова; Российская медицинская академия непрерывного профессионального образованияРоссияPirogov Russian National Research Medical University; Russian Medical Academy of Continuous Professional EducationRussian Federation2023201020230163340Copyright © Гиляревский С.Р., 20232023Гиляревский С.Р.Gilyarevskiy S.R.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.med-sovet.pro/jour/article/view/7786

Статья посвящена современной тактике снижения концентрации триглицеридов (ТГ) в крови. Необходимость обсуждения показаний к использованию гиполипидемической терапии у пациентов с гипертриглицеридемией обусловлена появлением новой доказательной информации. В статье приводятся данные о связи повышенной концентрации ТГ в крови с риском развития осложнений сердечно-сосудистых заболеваний (ССЗ), а также панкреатита. Рассматриваются механизмы метаболизма ТГ, которые могут обусловливать связь между повышенным уровнем ТГ в крови и риском развития осложнений ССЗ. Обсуждаются результаты крупных рандомизированных клинических исследований, в том числе недавно завершенных, на которых основываются современные клинические рекомендации по использованию препаратов, снижающих концентрацию ТГ. Рассматриваются показания к использованию фибратов у пациентов с повышенным уровнем ТГ в крови в различных клинических ситуациях. В статье подчеркивается, что в настоящее время в Российской Федерации недоступен препарат эфира икозапента, который в соответствии с последними вариантами международных рекомендаций считается препаратом первого ряда для снижения риска развития осложнений ССЗ у пациентов с установленным диагнозом ССЗ (т. е. с целью вторичной профилактики). В такой ситуации в нашей стране значение фенофибрата как средства для снижения концентарции ТГ в крови может оставаться достаточно высоким, в том числе и при вторичной профилактике осложнений ССЗ. Появление на фармацевтическом рынке Российской Федерации комбинированного препарата, содержащего розувастатин и фенофибрат, позволит повысить приверженность терапии при необходимости добавления фибрата к статину.

The article discusses the modern therapeutic approach to lowering blood triglyceride levels. The need to consider indications for the use of lipid-lowering therapy in patients with hypertriglyceridemia is caused by the emergence of new evidence-based information. The article describes how elevated blood TG levels are associated with the risk of developing cardiovascular (CV) complications, as well as pancreatitis. The mechanisms of TG metabolism that may regulate the relationship between elevated blood TG levels and the risk of developing CV complications are considered. The findings of large randomized clinical trials, including recent ones, which laid the foundation for the current clinical guidelines for the use of drugs to lower triglycerides levels, are discussed. Indications for fibrate therapy in patients with elevated blood TG levels in various clinical situations are considered. The article emphasizes that the icosapent ethyl ester drug is not currently available in the Russian Federation. According to the latest versions of international guidelines, it is considered a first-line drug to reduce the risk of developing CV complications in patients with an established diagnosis of CVD (i.e. for the purpose of secondary prevention). In this context, the significance of fenofibrate as a drug to lower blood triglyceride levels, specifically in secondary prevention of CV complications, can remain quite high in our country. The appearance of a rosuvastatin and fenofibrate combination drug on the pharmaceutical market of the Russian Federation will increase adherence to the therapy, if a fibrate is required to be added to statin therapy.

триглицеридыфенофибратсердечно-сосудистые заболеванияостаточный рискпервичная профилактикавторичная профилактикапанкреатитtriglyceridesfenofibratecardiovascular diseaseresidual riskprimary preventionsecondary preventionpancreatitisReferencesWatts GF, Ooi EM, Chan DC. Demystifying the management of hypertriglyceridaemia. Nat Rev Cardiol. 2013;10(11):648–661. https://doi.org/10.1038/nrcardio.2013.140.Watts GF, Ooi EM, Chan DC. Demystifying the management of hypertriglyceridaemia. Nat Rev Cardiol. 2013;10(11):648–661. https://doi.org/10.1038/nrcardio.2013.140.Miller M, Stone NJ, Ballantyne C, Bittner V, Criqui MH, Ginsberg HN et al. Triglycerides and cardiovascular disease: a scientific statement from the American Heart Association. Circulation. 2011;123(20):2292–2333. https://doi.org/10.1161/CIR.0b013e3182160726.Miller M, Stone NJ, Ballantyne C, Bittner V, Criqui MH, Ginsberg HN et al. Triglycerides and cardiovascular disease: a scientific statement from the American Heart Association. Circulation. 2011;123(20):2292–2333. https://doi.org/10.1161/CIR.0b013e3182160726.National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation. 2002;106(25):3143–3421. https://doi.org/10.1161/circ.106.25.3143.National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation. 2002;106(25):3143–3421. https://doi.org/10.1161/circ.106.25.3143.Chapman MJ, Ginsberg HN, Amarenco P, Andreotti F, Borén J, Catapano AL et al. Triglyceride-rich lipoproteins and high-density lipoprotein cholesterol in patients at high risk of cardiovascular disease: evidence and guidance for management. Eur Heart J. 2011;32(11):1345–1361. https://doi.org/10.1093/eurheartj/ehr112.Chapman MJ, Ginsberg HN, Amarenco P, Andreotti F, Borén J, Catapano AL et al. Triglyceride-rich lipoproteins and high-density lipoprotein cholesterol in patients at high risk of cardiovascular disease: evidence and guidance for management. Eur Heart J. 2011;32(11):1345–1361. https://doi.org/10.1093/eurheartj/ehr112.Leiter LA, Lundman P, da Silva PM, Drexel H, Jünger C, Gitt AK. Persistent lipid abnormalities in statin-treated patients with diabetes mellitus in Europe and Canada: results of the Dyslipidaemia International Study. Diabet Med. 2011;28(11):1343–1351. https://doi.org/10.1111/j.1464-5491.2011.03360.x.Leiter LA, Lundman P, da Silva PM, Drexel H, Jünger C, Gitt AK. Persistent lipid abnormalities in statin-treated patients with diabetes mellitus in Europe and Canada: results of the Dyslipidaemia International Study. Diabet Med. 2011;28(11):1343–1351. https://doi.org/10.1111/j.1464-5491.2011.03360.x.Drexel H, Tamargo J, Kaski JC, Lewis BS, Saely CH, Fraunberger P et al. Triglycerides Revisited: is Hypertriglyceridaemia a Necessary Therapeutic Target in Cardiovascular Disease? Eur Heart J Cardiovasc Pharmacother. 2023;9(6):570–582. https://doi.org/10.1093/ehjcvp/pvad044.Drexel H, Tamargo J, Kaski JC, Lewis BS, Saely CH, Fraunberger P et al. Triglycerides Revisited: is Hypertriglyceridaemia a Necessary Therapeutic Target in Cardiovascular Disease? Eur Heart J Cardiovasc Pharmacother. 2023;9(6):570–582. https://doi.org/10.1093/ehjcvp/pvad044.Wang N, Woodward M, Huffman MD, Rodgers A. Compounding Benefits of Cholesterol-Lowering Therapy for the Reduction of Major Cardiovascular Events: Systematic Review and Meta-Analysis. Circ Cardiovasc Qual Outcomes. 2022;15(6):e008552. https://doi.org/10.1161/CIRCOUTCOMES.121.008552.Wang N, Woodward M, Huffman MD, Rodgers A. Compounding Benefits of Cholesterol-Lowering Therapy for the Reduction of Major Cardiovascular Events: Systematic Review and Meta-Analysis. Circ Cardiovasc Qual Outcomes. 2022;15(6):e008552. https://doi.org/10.1161/CIRCOUTCOMES.121.008552.Boekholdt SM, Hovingh GK, Mora S, Arsenault BJ, Amarenco P, Pedersen TR et al. Very low levels of atherogenic lipoproteins and the risk for cardiovascular events: a meta-analysis of statin trials. J Am Coll Cardiol. 2014;64(5):485–494. https://doi.org/10.1016/j.jacc.2014.02.615.Boekholdt SM, Hovingh GK, Mora S, Arsenault BJ, Amarenco P, Pedersen TR et al. Very low levels of atherogenic lipoproteins and the risk for cardiovascular events: a meta-analysis of statin trials. J Am Coll Cardiol. 2014;64(5):485–494. https://doi.org/10.1016/j.jacc.2014.02.615.Raposeiras-Roubin S, Rosselló X, Oliva B, Fernández-Friera L, Mendiguren JM, Andrés V et al. Triglycerides and Residual Atherosclerotic Risk. J Am Coll Cardiol. 2021;77(24):3031–3041. https://doi.org/10.1016/j.jacc.2021.04.059.Raposeiras-Roubin S, Rosselló X, Oliva B, Fernández-Friera L, Mendiguren JM, Andrés V et al. Triglycerides and Residual Atherosclerotic Risk. J Am Coll Cardiol. 2021;77(24):3031–3041. https://doi.org/10.1016/j.jacc.2021.04.059.Vallejo-Vaz AJ, Corral P, Schreier L, Ray KK. Triglycerides and residual risk. Curr Opin Endocrinol Diabetes Obes. 2020;27(2):95–103. https://doi.org/10.1097/MED.0000000000000530.Vallejo-Vaz AJ, Corral P, Schreier L, Ray KK. Triglycerides and residual risk. Curr Opin Endocrinol Diabetes Obes. 2020;27(2):95–103. https://doi.org/10.1097/MED.0000000000000530.Goldstein JL, Brown MS. The LDL receptor. Arterioscler Thromb Vasc Biol. 2009;29(4):431–438. https://doi.org/10.1161/ATVBAHA.108.179564.Goldstein JL, Brown MS. The LDL receptor. Arterioscler Thromb Vasc Biol. 2009;29(4):431–438. https://doi.org/10.1161/ATVBAHA.108.179564.Saeed A, Feofanova EV, Yu B, Sun W, Virani SS, Nambi V et al. RemnantLike Particle Cholesterol, Low-Density Lipoprotein Triglycerides, and Incident Cardiovascular Disease. J Am Coll Cardiol. 2018;72(2):156–169. https://doi.org/10.1016/j.jacc.2018.04.050.Saeed A, Feofanova EV, Yu B, Sun W, Virani SS, Nambi V et al. RemnantLike Particle Cholesterol, Low-Density Lipoprotein Triglycerides, and Incident Cardiovascular Disease. J Am Coll Cardiol. 2018;72(2):156–169. https://doi.org/10.1016/j.jacc.2018.04.050.Toth PP. Triglyceride-rich lipoproteins as a causal factor for cardiovascular disease. Vasc Health Risk Manag. 2016;12:171–183. https://doi.org/10.2147/VHRM.S104369.Toth PP. Triglyceride-rich lipoproteins as a causal factor for cardiovascular disease. Vasc Health Risk Manag. 2016;12:171–183. https://doi.org/10.2147/VHRM.S104369.Hoogeveen RC, Ballantyne CM. Residual Cardiovascular Risk at Low LDL: Remnants, Lipoprotein(a), and Inflammation. Clin Chem. 2021;67(1):143–153. https://doi.org/10.1093/clinchem/hvaa252.Hoogeveen RC, Ballantyne CM. Residual Cardiovascular Risk at Low LDL: Remnants, Lipoprotein(a), and Inflammation. Clin Chem. 2021;67(1):143–153. https://doi.org/10.1093/clinchem/hvaa252.Mach F, Baigent C, Catapano AL, Koskinas KC, Casula M, Badimon L et al. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J. 2020;41(1):111–188. https://doi.org/10.1093/eurheartj/ehz455.Mach F, Baigent C, Catapano AL, Koskinas KC, Casula M, Badimon L et al. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J. 2020;41(1):111–188. https://doi.org/10.1093/eurheartj/ehz455.Berglund L, Brunzell JD, Goldberg AC, Goldberg IJ, Sacks F, Murad MH, Stalenhoef AF. Evaluation and treatment of hypertriglyceridemia: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2012;97(9):2969–2989. https://doi.org/10.1210/jc.2011-3213.Berglund L, Brunzell JD, Goldberg AC, Goldberg IJ, Sacks F, Murad MH, Stalenhoef AF. Evaluation and treatment of hypertriglyceridemia: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2012;97(9):2969–2989. https://doi.org/10.1210/jc.2011-3213.Anderson TJ, Grégoire J, Hegele RA, Couture P, Mancini GB, McPherson R et al. 2012 update of the Canadian Cardiovascular Society guidelines for the diagnosis and treatment of dyslipidemia for the prevention of cardiovascular disease in the adult. Can J Cardiol. 2013;29(2):151–167. https://doi.org/10.1016/j.cjca.2012.11.032.Anderson TJ, Grégoire J, Hegele RA, Couture P, Mancini GB, McPherson R et al. 2012 update of the Canadian Cardiovascular Society guidelines for the diagnosis and treatment of dyslipidemia for the prevention of cardiovascular disease in the adult. Can J Cardiol. 2013;29(2):151–167. https://doi.org/10.1016/j.cjca.2012.11.032.Teramoto T, Sasaki J, Ishibashi S, Birou S, Daida H, Dohi S et al. Executive summary of the Japan Atherosclerosis Society (JAS) guidelines for the diagnosis and prevention of atherosclerotic cardiovascular diseases in Japan – 2012 version. J Atheroscler Thromb. 2013;20(6):517–523. https://doi.org/10.5551/jat.15792.Teramoto T, Sasaki J, Ishibashi S, Birou S, Daida H, Dohi S et al. Executive summary of the Japan Atherosclerosis Society (JAS) guidelines for the diagnosis and prevention of atherosclerotic cardiovascular diseases in Japan – 2012 version. J Atheroscler Thromb. 2013;20(6):517–523. https://doi.org/10.5551/jat.15792.Bhatt DL, Steg PG, Miller M, Brinton EA, Jacobson TA, Ketchum SB et al. Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia. N Engl J Med. 2019;380(1):11–22. https://doi.org/10.1056/NEJMoa1812792.Bhatt DL, Steg PG, Miller M, Brinton EA, Jacobson TA, Ketchum SB et al. Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia. N Engl J Med. 2019;380(1):11–22. https://doi.org/10.1056/NEJMoa1812792.Keech A, Simes RJ, Barter P, Best J, Scott R, Taskinen MR et al. Effects of long-term fenofibrate therapy on cardiovascular events in 9795 people with type 2 diabetes mellitus (the FIELD study): randomised controlled trial. Lancet. 2005;366(9500):1849–1861. https://doi.org/10.1016/S0140-6736(05)67667-2.Keech A, Simes RJ, Barter P, Best J, Scott R, Taskinen MR et al. Effects of long-term fenofibrate therapy on cardiovascular events in 9795 people with type 2 diabetes mellitus (the FIELD study): randomised controlled trial. Lancet. 2005;366(9500):1849–1861. https://doi.org/10.1016/S0140-6736(05)67667-2.Ginsberg HN, Elam MB, Lovato LC, Crouse JR 3rd, Leiter LA, Linz P et al. Effects of combination lipid therapy in type 2 diabetes mellitus. N Engl J Med. 2010;362(17):1563–1574. https://doi.org/10.1056/NEJMoa1001282.Ginsberg HN, Elam MB, Lovato LC, Crouse JR 3rd, Leiter LA, Linz P et al. Effects of combination lipid therapy in type 2 diabetes mellitus. N Engl J Med. 2010;362(17):1563–1574. https://doi.org/10.1056/NEJMoa1001282.Zhu L, Hayen A, Bell KJL. Legacy effect of fibrate add-on therapy in diabetic patients with dyslipidemia: a secondary analysis of the ACCORDION study. Cardiovasc Diabetol. 2020;19(1):28. https://doi.org/10.1186/s12933-020-01002-x.Zhu L, Hayen A, Bell KJL. Legacy effect of fibrate add-on therapy in diabetic patients with dyslipidemia: a secondary analysis of the ACCORDION study. Cardiovasc Diabetol. 2020;19(1):28. https://doi.org/10.1186/s12933-020-01002-x.Banach M, Burchardt P, Chlebus K, Dobrowolski P, Dudek D, Dyrbuś K et al. PoLA/CFPiP/PCS/PSLD/PSD/PSH guidelines on diagnosis and therapy of lipid disorders in Poland 2021. Arch Med Sci. 2021;17(6):1447–1547. https://doi.org/10.5114/aoms/141941.Banach M, Burchardt P, Chlebus K, Dobrowolski P, Dudek D, Dyrbuś K et al. PoLA/CFPiP/PCS/PSLD/PSD/PSH guidelines on diagnosis and therapy of lipid disorders in Poland 2021. Arch Med Sci. 2021;17(6):1447–1547. https://doi.org/10.5114/aoms/141941.Averna M, Banach M, Bruckert E, Drexel H, Farnier M, Gaita D et al. Practical guidance for combination lipid-modifying therapy in highand very-high-risk patients: A statement from a European Atherosclerosis Society Task Force. Atherosclerosis. 2021;325:99–109. https://doi.org/10.1016/j.atherosclerosis.2021.03.039.Averna M, Banach M, Bruckert E, Drexel H, Farnier M, Gaita D et al. Practical guidance for combination lipid-modifying therapy in highand very-high-risk patients: A statement from a European Atherosclerosis Society Task Force. Atherosclerosis. 2021;325:99–109. https://doi.org/10.1016/j.atherosclerosis.2021.03.039.Ежов МВ, Кухарчук ВВ, Сергиенко ИВ, Алиева АС, Анциферов МБ, Аншелес АА и др. Нарушения липидного обмена: клинические рекомендации. М.; 2023. 103 с. Режим доступа: https://cr.minzdrav.gov.ru/recomend/752_1.Ежов МВ, Кухарчук ВВ, Сергиенко ИВ, Алиева АС, Анциферов МБ, Аншелес АА и др. Нарушения липидного обмена: клинические рекомендации. М.; 2023. 103 с. Режим доступа: https://cr.minzdrav.gov.ru/recomend/752_1.Fruchart JC. Selective peroxisome proliferator-activated receptor α modulators (SPPARMα): the next generation of peroxisome proliferatoractivated receptor α-agonists. Cardiovasc Diabetol. 2013;12:82. https://doi.org/10.1186/1475-2840-12-82.Fruchart JC. Selective peroxisome proliferator-activated receptor α modulators (SPPARMα): the next generation of peroxisome proliferatoractivated receptor α-agonists. Cardiovasc Diabetol. 2013;12:82. https://doi.org/10.1186/1475-2840-12-82.Yamashita S, Masuda D, Matsuzawa Y. Clinical Applications of a Novel Selective PPARα Modulator, Pemafibrate, in Dyslipidemia and Metabolic Diseases. J Atheroscler Thromb. 2019;26(5):389–402. https://doi.org/10.5551/jat.48918.Yamashita S, Masuda D, Matsuzawa Y. Clinical Applications of a Novel Selective PPARα Modulator, Pemafibrate, in Dyslipidemia and Metabolic Diseases. J Atheroscler Thromb. 2019;26(5):389–402. https://doi.org/10.5551/jat.48918.Das Pradhan A, Glynn RJ, Fruchart JC, MacFadyen JG, Zaharris ES, Everett BM et al. Triglyceride Lowering with Pemafibrate to Reduce Cardiovascular Risk. N Engl J Med. 2022;387(21):1923–1934. https://doi.org/10.1056/NEJMoa2210645.Das Pradhan A, Glynn RJ, Fruchart JC, MacFadyen JG, Zaharris ES, Everett BM et al. Triglyceride Lowering with Pemafibrate to Reduce Cardiovascular Risk. N Engl J Med. 2022;387(21):1923–1934. https://doi.org/10.1056/NEJMoa2210645.Drexel H, Saely CH, Agewall S. Fibrates: one more lost paradise in lipid treatment. Eur Heart J Cardiovasc Pharmacother. 2023;9(2):121. https://doi.org/10.1093/ehjcvp/pvac072.Drexel H, Saely CH, Agewall S. Fibrates: one more lost paradise in lipid treatment. Eur Heart J Cardiovasc Pharmacother. 2023;9(2):121. https://doi.org/10.1093/ehjcvp/pvac072.Virani SS. The Fibrates Story – A Tepid End to a PROMINENT Drug. N Engl J Med. 2022;387(21):1991–1992. https://doi.org/10.1056/NEJMe2213208.Virani SS. The Fibrates Story – A Tepid End to a PROMINENT Drug. N Engl J Med. 2022;387(21):1991–1992. https://doi.org/10.1056/NEJMe2213208.Sherratt SCR, Libby P, Budoff MJ, Bhatt DL, Mason RP. Role of Omega-3 Fatty Acids in Cardiovascular Disease: the Debate Continues. Curr Atheroscler Rep. 2023;25(1):1–17. https://doi.org/10.1007/s11883-022-01075-x.Sherratt SCR, Libby P, Budoff MJ, Bhatt DL, Mason RP. Role of Omega-3 Fatty Acids in Cardiovascular Disease: the Debate Continues. Curr Atheroscler Rep. 2023;25(1):1–17. https://doi.org/10.1007/s11883-022-01075-x.Arai H, Yamashita S, Yokote K, Araki E, Suganami H, Ishibashi S. Efficacy and Safety of Pemafibrate Versus Fenofibrate in Patients with High Triglyceride and Low HDL Cholesterol Levels: A Multicenter, PlaceboControlled, Double-Blind, Randomized Trial. J Atheroscler Thromb. 2018;25(6):521–538. https://doi.org/10.5551/jat.44412.Arai H, Yamashita S, Yokote K, Araki E, Suganami H, Ishibashi S. Efficacy and Safety of Pemafibrate Versus Fenofibrate in Patients with High Triglyceride and Low HDL Cholesterol Levels: A Multicenter, PlaceboControlled, Double-Blind, Randomized Trial. J Atheroscler Thromb. 2018;25(6):521–538. https://doi.org/10.5551/jat.44412.Sacks FM, Carey VJ, Fruchart JC. Combination lipid therapy in type 2 diabetes. N Engl J Med. 2010;363(7):692–694. https://doi.org/10.1056/NEJMc1006407.Sacks FM, Carey VJ, Fruchart JC. Combination lipid therapy in type 2 diabetes. N Engl J Med. 2010;363(7):692–694. https://doi.org/10.1056/NEJMc1006407.Jun M, Foote C, Lv J, Neal B, Patel A, Nicholls SJ et al. Effects of fibrates on cardiovascular outcomes: a systematic review and meta-analysis. Lancet. 2010;375(9729):1875–1884. https://doi.org/10.1016/S0140-6736(10)60656-3.Jun M, Foote C, Lv J, Neal B, Patel A, Nicholls SJ et al. Effects of fibrates on cardiovascular outcomes: a systematic review and meta-analysis. Lancet. 2010;375(9729):1875–1884. https://doi.org/10.1016/S0140-6736(10)60656-3.Drexel H, Pocock SJ, Lewis BS, Saely CH, Kaski JC, Rosano GMC et al. Subgroup analyses in randomized clinical trials: value and limitations. Review #3 on important aspects of randomized clinical trials in cardiovascular pharmacotherapy. Eur Heart J Cardiovasc Pharmacother. 2022;8(3):302–310. https://doi.org/10.1093/ehjcvp/pvab048.Drexel H, Pocock SJ, Lewis BS, Saely CH, Kaski JC, Rosano GMC et al. Subgroup analyses in randomized clinical trials: value and limitations. Review #3 on important aspects of randomized clinical trials in cardiovascular pharmacotherapy. Eur Heart J Cardiovasc Pharmacother. 2022;8(3):302–310. https://doi.org/10.1093/ehjcvp/pvab048.Moulin P, Dufour R, Averna M, Arca M, Cefalù AB, Noto D et al. Identification and diagnosis of patients with familial chylomicronaemia syndrome (FCS): Expert panel recommendations and proposal of an “FCS score”. Atherosclerosis. 2018;275:265–272. https://doi.org/10.1016/j.atherosclerosis.2018.06.814.Moulin P, Dufour R, Averna M, Arca M, Cefalù AB, Noto D et al. Identification and diagnosis of patients with familial chylomicronaemia syndrome (FCS): Expert panel recommendations and proposal of an “FCS score”. Atherosclerosis. 2018;275:265–272. https://doi.org/10.1016/j.atherosclerosis.2018.06.814.Meyers CD, Tremblay K, Amer A, Chen J, Jiang L, Gaudet D. Effect of the DGAT1 inhibitor pradigastat on triglyceride and apoB48 levels in patients with familial chylomicronemia syndrome. Lipids Health Dis. 2015;14:8. https://doi.org/10.1186/s12944-015-0006-5.Meyers CD, Tremblay K, Amer A, Chen J, Jiang L, Gaudet D. Effect of the DGAT1 inhibitor pradigastat on triglyceride and apoB48 levels in patients with familial chylomicronemia syndrome. Lipids Health Dis. 2015;14:8. https://doi.org/10.1186/s12944-015-0006-5.Lindkvist B, Appelros S, Regnér S, Manjer J. A prospective cohort study on risk of acute pancreatitis related to serum triglycerides, cholesterol and fasting glucose. Pancreatology. 2012;12(4):317–324. https://doi.org/10.1016/j.pan.2012.05.002.Lindkvist B, Appelros S, Regnér S, Manjer J. A prospective cohort study on risk of acute pancreatitis related to serum triglycerides, cholesterol and fasting glucose. Pancreatology. 2012;12(4):317–324. https://doi.org/10.1016/j.pan.2012.05.002.Hegele RA, Ginsberg HN, Chapman MJ, Nordestgaard BG, Kuivenhoven JA, Averna M et al. The polygenic nature of hypertriglyceridaemia: implications for definition, diagnosis, and management. Lancet Diabetes Endocrinol. 2014;2(8):655–666. https://doi.org/10.1016/S2213-8587(13)70191-8.Hegele RA, Ginsberg HN, Chapman MJ, Nordestgaard BG, Kuivenhoven JA, Averna M et al. The polygenic nature of hypertriglyceridaemia: implications for definition, diagnosis, and management. Lancet Diabetes Endocrinol. 2014;2(8):655–666. https://doi.org/10.1016/S2213-8587(13)70191-8.Ewald N, Hardt PD, Kloer HU. Severe hypertriglyceridemia and pancreatitis: presentation and management. Curr Opin Lipidol. 2009;20(6):497–504. https://doi.org/10.1097/MOL.0b013e3283319a1d.Ewald N, Hardt PD, Kloer HU. Severe hypertriglyceridemia and pancreatitis: presentation and management. Curr Opin Lipidol. 2009;20(6):497–504. https://doi.org/10.1097/MOL.0b013e3283319a1d.Gryn SE, Hegele RA. Novel therapeutics in hypertriglyceridemia. Curr Opin Lipidol. 2015;26(6):484–491. https://doi.org/10.1097/MOL.0000000000000231.Gryn SE, Hegele RA. Novel therapeutics in hypertriglyceridemia. Curr Opin Lipidol. 2015;26(6):484–491. https://doi.org/10.1097/MOL.0000000000000231.Qamar A, Libby P, Bhatt DL. Targeting RNA to lower triglycerides: long strides from short molecules. Eur Heart J. 2019;40(33):2797–2800. https://doi.org/10.1093/eurheartj/ehz321.Qamar A, Libby P, Bhatt DL. Targeting RNA to lower triglycerides: long strides from short molecules. Eur Heart J. 2019;40(33):2797–2800. https://doi.org/10.1093/eurheartj/ehz321.Gaudet D, Alexander VJ, Baker BF, Brisson D, Tremblay K, Singleton W et al. Antisense Inhibition of Apolipoprotein C-III in Patients with Hypertriglyceridemia. N Engl J Med. 2015;373(5):438–447. https://doi.org/10.1056/NEJMoa1400283.Gaudet D, Alexander VJ, Baker BF, Brisson D, Tremblay K, Singleton W et al. Antisense Inhibition of Apolipoprotein C-III in Patients with Hypertriglyceridemia. N Engl J Med. 2015;373(5):438–447. https://doi.org/10.1056/NEJMoa1400283.Calcaterra I, Lupoli R, Di Minno A, Di Minno MND. Volanesorsen to treat severe hypertriglyceridaemia: A pooled analysis of randomized controlled trials. Eur J Clin Invest. 2022;52(11):e13841. https://doi.org/10.1111/eci.13841.Calcaterra I, Lupoli R, Di Minno A, Di Minno MND. Volanesorsen to treat severe hypertriglyceridaemia: A pooled analysis of randomized controlled trials. Eur J Clin Invest. 2022;52(11):e13841. https://doi.org/10.1111/eci.13841.Stitziel NO, Khera AV, Wang X, Bierhals AJ, Vourakis AC, Sperry AE et al. ANGPTL3 Deficiency and Protection Against Coronary Artery Disease. J Am Coll Cardiol. 2017;69(16):2054–2063. https://doi.org/10.1016/j.jacc.2017.02.030.Stitziel NO, Khera AV, Wang X, Bierhals AJ, Vourakis AC, Sperry AE et al. ANGPTL3 Deficiency and Protection Against Coronary Artery Disease. J Am Coll Cardiol. 2017;69(16):2054–2063. https://doi.org/10.1016/j.jacc.2017.02.030.Wang Y, Gusarova V, Banfi S, Gromada J, Cohen JC, Hobbs HH. Inactivation of ANGPTL3 reduces hepatic VLDL-triglyceride secretion. J Lipid Res. 2015;56(7):1296–1307. https://doi.org/10.1194/jlr.M054882.Wang Y, Gusarova V, Banfi S, Gromada J, Cohen JC, Hobbs HH. Inactivation of ANGPTL3 reduces hepatic VLDL-triglyceride secretion. J Lipid Res. 2015;56(7):1296–1307. https://doi.org/10.1194/jlr.M054882.Laufs U, Parhofer KG, Ginsberg HN, Hegele RA. Clinical review on triglycerides. Eur Heart J. 2020;41(1):99–109c. https://doi.org/10.1093/eurheartj/ehz785.Laufs U, Parhofer KG, Ginsberg HN, Hegele RA. Clinical review on triglycerides. Eur Heart J. 2020;41(1):99–109c. https://doi.org/10.1093/eurheartj/ehz785.

The authors declare that there are no conflicts of interest present.