Pharmacological treatment options for severe hypertriglyceridemia and familial chylomicronemia syndrome

References

• Sathiyakumar V, Park JW, Toth P, et al. Modern-day prevalence of Fredricksen-Levy-Lees dyslipidemias: more common than you think. J Am Coll Cardiol. 2018;71(11 supplement):1772.
   Web of Science ®Google Scholar
• Brunzell JD, Bierman EL. Chylomicronemia syndrome. Interaction of genetic and acquired hypertriglyceridemia. Med Clin North Am. 1982;66(2):455–468.
   PubMed Web of Science ®Google Scholar
• Stroes E, Moulin P, Parhofer KG, et al. Diagnostic algorithm for familial chylomicronemia syndrome. Atheroscler Suppl. 2017;23:1–7.
   PubMed Web of Science ®Google Scholar
• Hegele RA, Berberich AJ, Ban MR, et al. Clinical and biochemical features of different molecular etiologies of familial chylomicronemia. J Clin Lipidol. 2018 Apr 4. pii: S1933-2874(18)30198-3. doi: 10.1016/j.jacl.2018.03.093. [Epub ahead of print]
   Google Scholar
• Brahm AJ, Hegele RA. Chylomicronaemia – current diagnosis and future therapies. Nat Rev Endocrinol. 2015;11(6):352–362.
   PubMed Web of Science ®Google Scholar
• Hegele RA, Ginsberg HN, Chapman MJ, et al. The polygenic nature of hypertriglyceridaemia: implications for definition, diagnosis, and management. Lancet Diabetes Endocrinol. 2014;2(8):655–666.
   PubMed Web of Science ®Google Scholar
• Demignot S, Beilstein F, Morel E. Triglyceride-rich lipoproteins and cytosolic lipid droplets in enterocytes: key players in intestinal physiology and metabolic disorders. Biochimie. 2014;96:48–55.
   PubMed Web of Science ®Google Scholar
• The ZR. ANGPTL3-4-8 model, a molecular mechanism for triglyceride trafficking. Open Biol. 2016;6(4):150272.
   PubMed Web of Science ®Google Scholar
• Angiopoietin-Like KS. 3 in lipoprotein metabolism. Nat Rev Endocrinol. 2017;13(12):731–739.
   PubMed Web of Science ®Google Scholar
• Mendivil CO, Zheng C, Furtado J, et al. Metabolism of very-low-density lipoprotein and low-density lipoprotein containing apolipoprotein C-III and not other small apolipoproteins. Arterioscler Thromb Vasc Biol. 2010;30(2):239–245.
   PubMed Web of Science ®Google Scholar
• Vors C, Pineau G, Drai J, et al. Postprandial endotoxemia linked with chylomicrons and lipopolysaccharides handling in obese versus lean men: a lipid dose-effect trial. J Clin Endocrinol Metab. 2015;100(9):3427–3435.
   PubMed Web of Science ®Google Scholar
• Viljoen A, Wierzbicki AS. Diagnosis and treatment of severe hypertriglyceridemia. Expert Rev Cardiovasc Ther. 2012;10(4):505–514.
   PubMedGoogle Scholar
• Hayne CK, Yumerefendi H, Cao L, et al. We FRET so you don’t have to: new models of the lipoprotein lipase dimer. Biochemistry. 2018;57(2):241–254.
   PubMed Web of Science ®Google Scholar
• Brunzell JD, Deeb SS. Familial lipoprotein lipase deficiency, apoC-II deficiency, and hepatic lipase deficiency. In: Scriver CR, Beaudet AL, Sly WS, editors. The metabolic & molecular bases of inherited disease. New York (NY): McGraw-Hill; 2001. p. 2789–2816.
   Google Scholar
• Lee JH, Giannikopoulos P, Duncan SA, et al. The transcription factor cyclic AMP-responsive element-binding protein H regulates triglyceride metabolism. Nat Med. 2011;17(7):812–815.
   PubMed Web of Science ®Google Scholar
• Fong LG, Young SG, Beigneux AP, et al. GPIHBP1 and plasma triglyceride metabolism. Trends Endocrinol Metab. 2016;27(7):455–469.
   PubMed Web of Science ®Google Scholar
• Beigneux AP, Miyashita K, Ploug M, et al. Autoantibodies against GPIHBP1 as a cause of hypertriglyceridemia. N Engl J Med. 2017;376(17):1647–1658.
   PubMed Web of Science ®Google Scholar
• Brunzell JD. Clinical practice. hypertriglyceridemia. N Engl J Med. 2007;357(10):1009–1017.
   PubMed Web of Science ®Google Scholar
• Ooi EM, Russell BS, Olson E, et al. Apolipoprotein B-100-containing lipoprotein metabolism in subjects with lipoprotein lipase gene mutations. Arterioscler Thromb Vasc Biol. 2012;32(2):459–466.
   PubMed Web of Science ®Google Scholar
• Burnett JR, Hooper AJ, Hegele RA. Familial lipoprotein lipase deficiency. In: Pagon RA, Bird TC, Dolan CR, et al., editors. Gene reviews. Seattle, WA, USA: University of Washington; 2009.
   Google Scholar
• Davidson M, Stevenson M, Hsieh A, et al. The burden of familial chylomicronemia syndrome: interim results from the IN-FOCUS study. Expert Rev Cardiovasc Ther. 2017;15(5):415–423.
   PubMed Web of Science ®Google Scholar
• Khera AV, Won HH, Peloso GM, et al. Association of rare and common variation in the lipoprotein lipase gene with coronary artery disease. JAMA. 2017;317(9):937–946.
   PubMed Web of Science ®Google Scholar
• Johansen CT, Wang J, Lanktree MB, et al. Excess of rare variants in genes identified by genome-wide association study of hypertriglyceridemia. Nat Genet. 2010;42(8):684–687.
   PubMed Web of Science ®Google Scholar
• Do R, Stitziel NO, Won HH, et al. Exome sequencing identifies rare LDLR and APOA5 alleles conferring risk for myocardial infarction. Nature. 2015;518(7537):102–106.
   PubMed Web of Science ®Google Scholar
• Gaudet D, de Wal J, Tremblay K, et al. Review of the clinical development of alipogene tiparvovec gene therapy for lipoprotein lipase deficiency. Atheroscler Suppl. 2010;11(1):55–60.
   PubMed Web of Science ®Google Scholar
• Lloret-Linares C, Pelletier AL, Czernichow S, et al. Acute pancreatitis in a cohort of 129 patients referred for severe hypertriglyceridemia. Pancreas. 2008;37(1):12–13.
   Web of Science ®Google Scholar
• Rabar S, Harker M, O’Flynn N, et al. Lipid modification and cardiovascular risk assessment for the primary and secondary prevention of cardiovascular disease: summary of updated NICE guidance. BMJ. 2014;349:g4356.
   PubMed Web of Science ®Google Scholar
• Chapman MJ, Ginsberg HN, Amarenco P, 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.
   PubMed Web of Science ®Google Scholar
• Lennertz A, Parhofer KG, Samtleben W, et al. Therapeutic plasma exchange in patients with chylomicronemia syndrome complicated by acute pancreatitis. Ther Apher. 1999;3(3):227–233.
   PubMedGoogle Scholar
• Heaney AP, Sharer N, Rameh B, et al. Prevention of recurrent pancreatitis in familial lipoprotein lipase deficiency with high-dose antioxidant therapy. J Clin Endocrinol Metab. 1999;84(4):1203–1205.
   PubMed Web of Science ®Google Scholar
• Viljoen A, Wierzbicki AS. Potential options to treat hypertriglyceridaemia. Curr Drug Targets. 2009;10(4):356–362.
   PubMed Web of Science ®Google Scholar
• Williams CM. Dietary interventions affecting chylomicron and chylomicron remnant clearance. Atherosclerosis. 1998;141(Suppl 1):S87–S92.
   PubMedGoogle Scholar
• Ahmad Z, Wilson DP. Familial chylomicronemia syndrome and response to medium-chain triglyceride therapy in an infant with novel mutations in GPIHBP1. J Clin Lipidol. 2014;8(6):635–639.
   PubMed Web of Science ®Google Scholar
• Rouis M, Dugi KA, Previato L, et al. Therapeutic response to medium-chain triglycerides and omega-3 fatty acids in a patient with the familial chylomicronemia syndrome. Arterioscler Thromb Vasc Biol. 1997;17(7):1400–1406.
   PubMed Web of Science ®Google Scholar
• Santamarina-Fojo S, Brewer HB Jr. The familial hyperchylomicronemia syndrome. New insights into underlying genetic defects. JAMA. 1991;265(7):904–908.
   PubMed Web of Science ®Google Scholar
• Harris WS, Connor WE, Alam N, et al. Reduction of postprandial triglyceridemia in humans by dietary n-3 fatty acids. J Lipid Res. 1988;29(11):1451–1460.
   PubMed Web of Science ®Google Scholar
• Chang CL, Seo T, Matsuzaki M, et al. n-3 fatty acids reduce arterial LDL-cholesterol delivery and arterial lipoprotein lipase levels and lipase distribution. Arterioscler Thromb Vasc Biol. 2009;29(4):555–561.
   PubMed Web of Science ®Google Scholar
• Ooi EM, Lichtenstein AH, Millar JS, et al. Effects of therapeutic lifestyle change diets high and low in dietary fish-derived FAs on lipoprotein metabolism in middle-aged and elderly subjects. J Lipid Res. 2012;53(9):1958–1967.
   PubMed Web of Science ®Google Scholar
• Oh DY, Talukdar S, Bae EJ, et al. GPR120 is an omega-3 fatty acid receptor mediating potent anti-inflammatory and insulin-sensitizing effects. Cell. 2010;142(5):687–698.
   PubMed Web of Science ®Google Scholar
• Park KS, Lim JW, Kim H. Inhibitory mechanism of omega-3 fatty acids in pancreatic inflammation and apoptosis. Ann N Y Acad Sci. 2009;1171:421–427.
   PubMed Web of Science ®Google Scholar
• Richter WO, Jacob BG, Ritter MM, et al. Treatment of primary chylomicronemia due to familial hypertriglyceridemia by omega-3 fatty acids. Metabolism. 1992;41(10):1100–1105.
   PubMed Web of Science ®Google Scholar
• Grogan K. Amarin excited as omega-3 drug impresses in Phase III. Leatherhead, Surrey, UK: PharmaTimes; 2010.
   Google Scholar
• Goldberg AP, Applebaum-Bowden DM, Bierman EL, et al. Increase in lipoprotein lipase during clofibrate treatment of hypertriglyceridemia in patients on hemodialysis. N Engl J Med. 1979;301(20):1073–1076.
   PubMed Web of Science ®Google Scholar
• Kersten S, Stienstra R. The role and regulation of the peroxisome proliferator activated receptor alpha in human liver. Biochimie. 2017;136:75–84.
   PubMed Web of Science ®Google Scholar
• Al-Shali K, Wang J, Fellows F, et al. Successful pregnancy outcome in a patient with severe chylomicronemia due to compound heterozygosity for mutant lipoprotein lipase. Clin Biochem. 2002;35(2):125–130.
   PubMed Web of Science ®Google Scholar
• Wierzbicki AS. FIELDS of dreams, fields of tears: a perspective on the fibrate trials. Int J Clin Pract. 2006;60(4):442–449.
   PubMed Web of Science ®Google Scholar
• Kamanna VS, Kashyap ML. Mechanism of action of niacin. Am J Cardiol. 2008;101(8A):20B–26B.
   PubMed Web of Science ®Google Scholar
• Hernandez C, Molusky M, Li Y, et al. Regulation of hepatic ApoC3 expression by PGC-1beta mediates hypolipidemic effect of nicotinic acid. Cell Metab. 2010;12(4):411–419.
   PubMed Web of Science ®Google Scholar
• Blasiole DA, Davis RA, Attie AD. The physiological and molecular regulation of lipoprotein assembly and secretion. Mol Biosyst. 2007;3(9):608–619.
   PubMed Web of Science ®Google Scholar
• Hanson J, Gille A, Zwykiel S, et al. Nicotinic acid- and monomethyl fumarate-induced flushing involves GPR109A expressed by keratinocytes and COX-2-dependent prostanoid formation in mice. J Clin Invest. 2010;120(8):2910–2919.
   PubMed Web of Science ®Google Scholar
• Lai E, Waters MG, Tata JR, et al. Effects of a niacin receptor partial agonist, MK-0354, on plasma free fatty acids, lipids, and cutaneous flushing in humans. J Clin Lipidol. 2008;2(5):375–383.
   PubMed Web of Science ®Google Scholar
• Vogt A, Kassner U, Hostalek U, et al. Evaluation of the safety and tolerability of prolonged-release nicotinic acid in a usual care setting: the NAUTILUS study. Curr Med Res Opin. 2006;22(2):417–425.
   PubMed Web of Science ®Google Scholar
• Carlson LA, Froberg S, Oro L. A case of massive hypertriglyceridemia corrected by nicotinic acid or nicotinamide therapy. Atherosclerosis. 1972;16(3):359–368.
   PubMed Web of Science ®Google Scholar
• Pang J, Chan DC, Hamilton SJ, et al. Effect of niacin on triglyceride-rich lipoprotein apolipoprotein B-48 kinetics in statin-treated patients with type 2 diabetes. Diabetes Obes Metab. 2016;18(4):384–391.
   PubMed Web of Science ®Google Scholar
• Stein EA, Lane M, Laskarzewski P. Comparison of statins in hypertriglyceridemia. Am J Cardiol. 1998;81(4A):66B–69B.
   PubMed Web of Science ®Google Scholar
• Bakker-Arkema RG, Davidson MH, Goldstein RJ, et al. Efficacy and safety of a new HMG-CoA reductase inhibitor, atorvastatin, in patients with hypertriglyceridemia. JAMA. 1996;275(2):128–133.
   PubMed Web of Science ®Google Scholar
• Watts GF, Barrett PH, Ji J, et al. Differential regulation of lipoprotein kinetics by atorvastatin and fenofibrate in subjects with the metabolic syndrome. Diabetes. 2003;52(3):803–811.
   PubMed Web of Science ®Google Scholar
• Wierzbicki AS, Reynolds TM. Familial hyperchylomicronaemia. Lancet. 1996;348(9040):1524–1525.
   PubMed Web of Science ®Google Scholar
• Wierzbicki AS, Morrell J, Hemsley D, et al. The effect of fibrate-statin combination therapy on cardiovascular events: a retrospective cohort analysis. Curr Med Res Opin. 2010;26(9):2141–2146.
   PubMed Web of Science ®Google Scholar
• Hogue JC, Lamarche B, Deshaies Y, et al. Differential effect of fenofibrate and atorvastatin on in vivo kinetics of apolipoproteins B-100 and B-48 in subjects with type 2 diabetes mellitus with marked hypertriglyceridemia. Metabolism. 2008;57(2):246–254.
   PubMed Web of Science ®Google Scholar
• Preiss D, MJ T, Welsh P, et al. Lipid-modifying therapies and risk of pancreatitis: a meta-analysis. JAMA. 2012;308(8):804–811.
   PubMed Web of Science ®Google Scholar
• Wierzbicki AS, Reynolds TM, Crook MA. Usefulness of Orlistat in the treatment of severe hypertriglyceridemia. Am J Cardiol. 2002;89(2):229–231.
   PubMed Web of Science ®Google Scholar
• Blackett P, Tryggestad J, Krishnan S, et al. Lipoprotein abnormalities in compound heterozygous lipoprotein lipase deficiency after treatment with a low-fat diet and orlistat. J Clin Lipidol. 2013;7(2):132–139.
   PubMed Web of Science ®Google Scholar
• Napier S, Thomas M. 36 year old man presenting with pancreatitis and a history of recent commencement of Orlistat case report. Nutr J. 2006;5:19.
   PubMed Web of Science ®Google Scholar
• Eleftheriadou I, Grigoropoulou P, Katsilambros N, et al. The effects of medications used for the management of diabetes and obesity on postprandial lipid metabolism. Curr Diabetes Rev. 2008;4(4):340–356.
   PubMedGoogle Scholar
• Chappuis B, Braun M, Stettler C, et al. Differential effect of pioglitazone (PGZ) and rosiglitazone (RGZ) on postprandial glucose and lipid metabolism in patients with type 2 diabetes mellitus: a prospective, randomized crossover study. Diabetes Metab Res Rev. 2007;23(5):392–399.
   PubMed Web of Science ®Google Scholar
• Al Majali K, Cooper MB, Staels B, et al. The effect of sensitisation to insulin with pioglitazone on fasting and postprandial lipid metabolism, lipoprotein modification by lipases, and lipid transfer activities in type 2 diabetic patients. Diabetologia. 2006;49(3):527–537.
   PubMed Web of Science ®Google Scholar
• Xiao C, Dash S, Morgantini C, et al. Sitagliptin, a DPP-4 inhibitor, acutely inhibits intestinal lipoprotein particle secretion in healthy humans. Diabetes. 2014;63(7):2394–2401.
   PubMed Web of Science ®Google Scholar
• Cuchel M, Meagher EA, du Toit Theron H, et al. Efficacy and safety of a microsomal triglyceride transfer protein inhibitor in patients with homozygous familial hypercholesterolaemia: a single-arm, open-label, phase 3 study. Lancet. 2013;381(9860):40–46.
   PubMed Web of Science ®Google Scholar
• Sacks FM, Stanesa M, Hegele RA. Severe hypertriglyceridemia with pancreatitis: thirteen years’ treatment with lomitapide. JAMA Intern Med. 2014;174(3):443–447.
   Web of Science ®Google Scholar
• Costet P. Molecular pathways and agents for lowering LDL-cholesterol in addition to statins. Pharmacol Ther. 2010;126(3):263–278.
   PubMed Web of Science ®Google Scholar
• Ganji SH, Tavintharan S, Zhu D, et al. Niacin noncompetitively inhibits DGAT2 but not DGAT1 activity in HepG2 cells. J Lipid Res. 2004;45(10):1835–1845.
   PubMed Web of Science ®Google Scholar
• Meyers CD, Tremblay K, Amer A, et al. Effect of the DGAT1 inhibitor pradigastat on triglyceride and apoB48 levels in patients with familial chylomicronemia syndrome. Lipids Health Dis. 2015;14:8.
   PubMed Web of Science ®Google Scholar
• Alexander IE, Cunningham SC, Logan GJ, et al. Potential of AAV vectors in the treatment of metabolic disease. Gene Ther. 2008;15(11):831–839.
   PubMed Web of Science ®Google Scholar
• Rader DJ. Gain-of-function mutations and therapeutic implications: lipoprotein lipase S447X to the rescue. Arterioscler Thromb Vasc Biol. 2005;25(10):2018–2019.
   PubMed Web of Science ®Google Scholar
• Wierzbicki AS, Viljoen A. Alipogene tiparvovec: gene therapy for lipoprotein lipase deficiency. Expert Opin Biol Ther. 2013;13(1):7–10.
   PubMed Web of Science ®Google Scholar
• Gaudet D, Methot J, Dery S, et al. Efficacy and long-term safety of alipogene tiparvovec (AAV1-LPL(S447X)) gene therapy for lipoprotein lipase deficiency: an open-label trial. Gene Therapy. 2013;20(4):361–369.
   Google Scholar
• Mingozzi F, Meulenberg JJ, Hui DJ, et al. AAV-1-mediated gene transfer to skeletal muscle in humans results in dose-dependent activation of capsid-specific T cells. Blood. 2009;114(10):2077–2086.
   PubMed Web of Science ®Google Scholar
• Carpentier AC, Frisch F, Labbe SM, et al. Effect of alipogene tiparvovec (AAV1-LPL(S447X)) on postprandial chylomicron metabolism in lipoprotein lipase-deficient patients. J Clin Endocrinol Metab. 2012;97(5):1635–1644.
   PubMed Web of Science ®Google Scholar
• Gaudet D, Stroes ES, Methot J, et al. Long-term retrospective analysis of gene therapy with alipogene tiparvovec and its effect on lipoprotein lipase deficiency-induced pancreatitis. Hum Gene Ther. 2016;27(11):916–925.
   PubMed Web of Science ®Google Scholar
• Jorgensen AB, Frikke-Schmidt R, Nordestgaard BG, et al. Loss-of-function mutations in APOC3 and risk of ischemic vascular disease. N Engl J Med. 2014;371(1):32–41.
   PubMed Web of Science ®Google Scholar
• Koska J, Yassine H, Trenchevska O, et al. Disialylated apolipoprotein C-III proteoform is associated with improved lipids in prediabetes and type 2 diabetes. J Lipid Res. 2016;57(5):894–905.
   PubMed Web of Science ®Google Scholar
• Graham MJ, Lee RG, Bell TA, et al. Antisense oligonucleotide inhibition of apolipoprotein C-III reduces plasma triglycerides in rodents, nonhuman primates, and humans. Circ Res. 2013;112(11):1479–1490.
   PubMed Web of Science ®Google Scholar
• Gaudet D, Alexander VJ, Baker BF, et al. Antisense inhibition of apolipoprotein C-III in patients with hypertriglyceridemia. N Engl J Med. 2015;373(5):438–447.
   PubMed Web of Science ®Google Scholar
• Yang X, Lee SR, Choi YS, et al. Reduction in lipoprotein-associated apoC-III levels following volanesorsen therapy: phase 2 randomized trial results. J Lipid Res. 2016;57(4):706–713.
   PubMed Web of Science ®Google Scholar
• Gaudet D, Brisson D, Tremblay K, et al. Targeting APOC3 in the familial chylomicronemia syndrome. N Engl J Med. 2014;371(23):2200–2206.
   PubMed Web of Science ®Google Scholar
• Gaudet D, Digenio A, Alexander V, et al. The APPROACH study: a randomized, double-blind, placebo-controlled, phase 3 study of volanesorsen administered subcutaneously to patients with familial chylomicronemia syndrome (FCS). Atherosclerosis. 2017;263:e10.
   Web of Science ®Google Scholar
• Chi X, Gatti P, Papoian T. Safety of antisense oligonucleotide and siRNA-based therapeutics. Drug Discov Today. 2017;22(5):823–833.
   PubMed Web of Science ®Google Scholar
• O’Connell C, Horwood K, Nadamuni M. Correction of refractory thrombocytopenia and anemia following withdrawal of extended release niacin. Am J Hematol. 2016;91(7):E318.
   PubMed Web of Science ®Google Scholar
• Tarrant JM, Dhawan P, Singh J, et al. Preclinical models of nicotinamide phosphoribosyltransferase inhibitor-mediated hematotoxicity and mitigation by co-treatment with nicotinic acid. Toxicol Mech Methods. 2015;25(3):201–211.
   PubMed Web of Science ®Google Scholar
• Cvetkovic Z, Suvajdzic-Vukovic N, Todorovic Z, et al. Simvastatin and amlodipine induced thrombocytopenia in the same patient: double trouble and a literature review. J Clin Pharm Ther. 2013;38(3):246–248.
   PubMed Web of Science ®Google Scholar
• Simpson-Haidaris PJ, Seweryniak KE, Spinelli SL, et al. A putative role for platelet-derived PPARgamma in vascular homeostasis demonstrated by anti-PPARgamma induction of bleeding, thrombocytopenia and compensatory megakaryocytopoiesis. J Biotechnol. 2010;150(3):417–427.
   PubMed Web of Science ®Google Scholar
• Preclinical HY. Clinical advances of GalNAc-decorated nucleic acid therapeutics. Mol Ther Nucleic Acids. 2017;6:116–132.
   PubMedGoogle Scholar
• Gaudet D, Gipe D, Hovingh K, et al. Safety and efficacy of evinacumab, a monoclonal antibody to ANGPTL3, in patients with homozygous familial hypercholesterolemia: a single-arm, open-label, proof-of-concept study. Atherosclerosis. 2017;263:e9.
   Web of Science ®Google Scholar
• Graham MJ, Lee RG, Brandt TA, et al. Cardiovascular and metabolic effects of ANGPTL3 antisense oligonucleotides. N Engl J Med. 2017;377(3):222–232.
   PubMed Web of Science ®Google Scholar
• Dewey FE, Gusarova V, O’Dushlaine C, et al. Inactivating variants in ANGPTL4 and risk of coronary artery disease. N Engl J Med. 2016;374(12):1123–1133.
   PubMed Web of Science ®Google Scholar
• Furtado JD, Wedel MK, Sacks FM. Antisense inhibition of apoB synthesis with mipomersen reduces plasma apoC-III and apoC-III-containing lipoproteins. J Lipid Res. 2012;53(4):784–791.
   PubMed Web of Science ®Google Scholar