Endotext: Triglyceride Lowering Drugs
Endotext. MDText.com, Inc.: South Dartmouth (MA).BOOK

Abstract

The two major goals of the treatment of hypertriglyceridemia are the prevention of cardiovascular disease and pancreatitis. Here we discuss the drugs used for the treatment of hypertriglyceridemia: (niacin, fibrates, omega-3-fatty acids, and apo CIII inhibitors. Niacin decreases total cholesterol, TGs (20-50% decrease), LDL-C, and Lp(a). Additionally, niacin decreases small dense LDL resulting in a shift to large, buoyant LDL particles. Moreover, niacin increases HDL-C. Skin flushing, insulin resistance, and other side effects have limited the use of niacin. The enthusiasm for niacin has greatly decreased with the failure of AIM-HIGH and HPS-2 Thrive to decrease cardiovascular events when niacin was added to statin therapy. The omega-3-fatty acids eicosapentaenoic acid (C20:5n-3) (EPA) and docosahexaenoic acid (C22:6n-3) (DHA) lower TGs by 10-50% but do not affect total cholesterol, HDL-C, or Lp(a). LDL-C may increase with EPA + DHA when the TG levels are markedly elevated (>500mg/dL). EPA alone does not increase LDL-C. Omega-3-fatty acids have few side effects, drug interactions, or contraindications. Numerous studies of low dose omega-3-fatty acids on cardiovascular outcomes have failed to demonstrate a benefit. However, in the JELIS, REDUCE-IT, and RESPECT-EPA trials high doses of EPA alone reduced cardiovascular events while in the STRENGTH and OMEMI trials high doses of EPA+DHA did not reduce cardiovascular events. Fibrates reduce TG levels by 25-50% and increase HDL-C by 5-20%. The effect on LDL-C is variable. If the TG levels are very high (>500mg/dL), fibrate therapy may result in an increase in LDL-C, whereas if TGs are not markedly elevated fibrates decrease LDL-C by 10-30%. Fibrates also reduce apolipoprotein B, LDL particle number, and non-HDL-C and there may be a shift from small dense LDL towards large LDL particles. Fibrates do not have any major effects on Lp(a). Monotherapy with fibrates appears to reduce cardiovascular events particularly in patients with high TG and low HDL-C levels. In contrast, in the ACCORD LIPID and PROMINENT trials the addition of fibrates to statin therapy did not reduce cardiovascular disease, which has reduced the enthusiasm for using fibrates to reduce cardiovascular disease. In patients with diabetes fibrates appear to slow the progression of microvascular disease (retinopathy, nephropathy, and amputations, ulcers, and gangrene. Antisense oligonucleotides, volanesorsen and olezarsen, inhibit the production of apolipoprotein C-III and decrease TG levels in patients with severe hypertriglyceridemia including patients with the familial chylomicronemia syndrome (FCS). Studies also suggest that apo CIII inhibitors reduce episodes of pancreatitis in patients with severe hypertriglyceridemia. Patients with FCS have also reported that apo C-III inhibitors improved symptoms and reduced interference of FCS with work/school responsibilities. Of concern has been decreases in platelet levels with 47% of patients treated with volanesorsen developing platelet counts below100 x 109/L, a side effect that is not observed with olezarsen. Thus, a number of drugs are available for the treatment of hypertriglyceridemia and may be employed when lifestyle changes are not sufficient. For complete coverage of all related areas of Endocrinology, please visit our on-line FREE web-text, WWW.ENDOTEXT.ORG.

Authors

Feingold KRProfessor of Medicine Emeritus, University of California, San Francisco, CA
Adler RAChief of Endocrinology and Metabolism at the Richmond Veterans Affairs Medical Center and Professor of Internal Medicine at Virginia Commonwealth University.
Ahmed SFDevelopmental Endocrinology Research Group, University of Glasgow, Glasgow, UK
Anawalt BChief of Medicine at the University of Washington Medical Center and Professor and Vice Chair of the Department of Medicine, University of Washington
Blackman MRSr. Physician Scientist, Washington DC VA Medical Center; Professor of Medicine & Rehabilitation Medicine, Georgetown University; Clinical Professor of Medicine, Biochemistry and Molecular Medicine, George Washington University; and Professor of Medicine (Part-time), Johns Hopkins University
Chrousos GProfessor of Pediatrics and Endocrinology, Division of Endocrinology, Metabolism and Diabetes, First Department of Pediatrics, National and Kapodistrian University of Athens Medical School, "Aghia Sophia" Children's Hospital, Athens, Greece
Corpas EM.D. Ph.D in Gerontology. Honorary Professor of Medicine, Universidad de Alcalá, Madrid. Consultant in Endocrinology, Hospital HLA Guadalajara (Spain).
de Herder WWProfessor of Endocrine Oncology, Erasmus MC and Erasmus MC Cancer Center, Rotterdam, the Netherlands
Dhatariya KConsultant in Diabetes, Endocrinology and General Medicine, Norfolk and Norwich University Hospitals NHS Foundation Trust and University of East Anglia, Norwich, UK.
Dungan KProfessor of Medicine, Division of Endocrinology, Diabetes, and Metabolism, Ohio State University
Hamilton EConsultant Endocrinologist at Fiona Stanley (FSH) and Fremantle Hospitals (FH) in Perth, Western Australia
Hofland JConsultant Endocrinologist, Erasmus MC and Erasmus MC Cancer Center, Rotterdam, the Netherlands
Jan de Beur SProfessor of Endocrinology and Chief of the Division of Endocrinology and Metabolism at the University of Virginia School of Medicine.
Kalra SConsultant Endocrinologist, Department of Endocrinology, Bharti Hospital, Karnal, India
Kaltsas GProfessor of General Medicine-Endocrinology, 1st Department of Propaedeutic Medicine, National and Kapodistrian University of Athens, Athens, Greece
Kapoor NProfessor of Endocrinology, Department of Endocrinology, Diabetes and Metabolism, Christian Medical College & Hospital, Vellore, Tamil Nadu, India, Melbourne School of Population and Global Health, Faculty of Medicine, Dentistry and Health Science, The University of Melbourne, Australia.
Kim MClinical Director of the Division of Endocrinology, Diabetes and Hypertension at Brigham and Women’s Hospital and an Assistant Professor of Medicine at Harvard Medical School. 18. Professor, Division of Endocrinology, Diabetes, Metabolism, Department of Medicine, The University of Tennessee Health Science Center, Memphis, TN, and University of Florida, Jacksonville, FL.
Koch CProfessor, The University of Tennessee Health Science Center, Memphis, Tennessee
Kopp PProfessor of Medicine and Chief of the Division of Endocrinology, Diabetology and Metabolism, University of Lausanne, Switzerland
Korbonits MProfessor of Endocrinology and Metabolism, Centre Lead for Endocrinology and Deputy Institute Director, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, England
Kovacs CSUniversity Research Professor and Professor of Medicine (Endocrinology and Metabolism), Obstetrics & Gynecology, and BioMedical Sciences, at Memorial University of Newfoundland in St. John’s, Newfoundland, Canada.
Kuohung WDirector of the Division of Reproductive Endocrinology at Boston Medical Center and an Associate Professor of Obstetrics and Gynecology at the Boston University School of Medicine
Laferrère BProfessor of Medicine, New York Nutrition Obesity Research Center, Division of Endocrinology, Department of Medicine, Columbia University Irving Medical Center, New York, NY, USA.
Levy MConsultant endocrinologist at University Hospitals of Leicester and Honorary Associate Professor at Leicester University
McGee EAProfessor of Obstetrics and Gynecology at the University of Vermont and Director of the Division of Reproductive Endocrinology and Infertility. Burlington, Vermont
McLachlan RDirector of Clinical Research, Hudson Institute of Medical Research; Consultant Endocrinologist, Monash Medical Centre, Melbourne, Australia
Muzumdar RAllan L. Drash Endowed Chair, Chief, Division of Endocrinology and Diabetes, UPMC Children’s Hospital of Pittsburgh, Professor of Pediatrics and Cell Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA
Purnell JProfessor of Medicine, Knight Cardiovascular Institute and the Division of Endocrinology, and Associate Director, Bob and Charlee Moore Institute for Nutrition and Wellness, Oregon Health and Science University, Portland, OR
Rey RCentro de Investigaciones Endocrinológicas “Dr. César Bergadá” (CEDIE), CONICET-FEI-División de Endocrinología, Hospital de Niños Ricardo Gutiérrez, Gallo 1330, C1425EFD Buenos Aires; and Departamento de Histología, Biología Celular, Embriología y Genética, Facultad de Medicina, Universidad de Buenos Aires, C1121ABG Buenos Aires, Argentina
Sahay RProfessor and Head of Department of Endocrinology, Osmania Medical College and Osmania General Hospital, Hyderabad, India.
Shah ASProfessor of Pediatrics, The University of Cincinnati, Department of Pediatrics and Cincinnati Children’s Hospital Medical Center, Division of Endocrinology, Cincinnati, OH, USA
Sperling MAProfessorial Lecturer, Division of Pediatric Endocrinology and Diabetes, Icahn School of Medicine at Mount Sinai, New York, NY. Emeritus Professor and Chair, Department of Pediatrics, University of Pittsburgh.
Stratakis CACSO, ELPEN, Inc. & Director, Research Institute, Athens, Greece & Senior Investigator, Human Genetics & Precision Medicine, FORTH (ITE), Heraklion, Greece. Emeritus Scientific Director & Senior Investigator, NICHD, NIH, Bethesda, MD, USA
Trence DLProfessor of Medicine, Emeritus, University of Washington, Seattle, WA
Wilson DPEndowed Chair, Cardiovascular Health and Risk Prevention, Pediatric Endocrinology and Diabetes, Cook Children's Medical Center, Fort Worth, TX

Publisher

MDText.com, Inc.
South Dartmouth (MA)

Language

eng

PubMed ID

28402615