Volume 8, Issue 6, November 2020, Page: 279-284
Familial Hypercholesterolemia: Improving Outcomes with Newer Agents
Saumitra Ray, Department of Cardiology, Vivekananda Institute of Medical Sciences, Kolkata, India
Biswarup Sarkar, Department of Cardiology, RG Kar Medical College and Hospital, Kolkata, India
Received: Sep. 23, 2020;       Accepted: Oct. 15, 2020;       Published: Nov. 16, 2020
DOI: 10.11648/j.ajim.20200806.17      View  32      Downloads  44
Familial hypercholesterolemia (FH) is one of the commonest autosomal dominant genetic disorders which affects lipoprotein metabolism in the body, causing thereby severe hypercholesterolemia, mainly contributed by high level of low density lipoprotein cholesterol (LDLc). This causes polyvascular premature atherosclerosis with significant mortality, especially in the homozygous form (HoFH), where affected persons die in their teens. There are well developed diagnostic criteria for FH but the index of suspicion of the physician needs to be high to detect heterozygous FH. As the blood LDLc values are very high, even the highest doses of statins cannot bring down the levels to optimum. Life style management should also be rigorously implemented. Ezetimibe imparts some extra 10 to 15% reduction of LDLc on top of maximally tolerated dose of statins. PCSK9I agents are recently approved for FH. They reduce LDLc further by 30-50%. The small interfering RNA, inclisiran, reduces LDLc by almost 60% and has shown clinical benefit in FH patients. Many other newer agents are in the pipe line of development. In extreme cases, plasmapheresis is life saving, but difficult to adopt as a regular long term treatment. Often the absolute target of LDLc level is not achieved even with all available measures, and a more than 50% reduction from the baseline value is all that can be attained. Early diagnosis by screening of first degree relatives of the index case helps to attain long term clinical benefit.
Familial Hypercholesterolemia, Premature Polyvascular Atherosclerotic Disease, Statin, Ezetimibe, PCSK9I, Inclisiran
To cite this article
Saumitra Ray, Biswarup Sarkar, Familial Hypercholesterolemia: Improving Outcomes with Newer Agents, American Journal of Internal Medicine. Special Issue: Dyslipidemia: Flash Back and Vision Ahead. Vol. 8, No. 6, 2020, pp. 279-284. doi: 10.11648/j.ajim.20200806.17
Copyright © 2020 Authors retain the copyright of this article.
This article is an open access article distributed under the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Fagge CH. Xanthomatous diseases of the skin. Trans Pathol Soc Lond 1873; 242-50.
Muller C. Angina pectoris in hereditary xanthomatosis. Arch Intern Med 1939; 64: 675-700.
Goldstein JL, Brown MS. Binding and degradation of low density lipoproteins by cultured human fibroblasts. Comparison of cells from a normal subject and from a patient with homozygous familial hypercholesterolemia. J Biol Chem 1974; 249: 5153-62.
Goldstein JL, Hobbs HH, Brown MS. Familial hypercholesterolemia. The metabolic and molecular bases of inherited disease. 8th ed. New York: McGraw-Hill, Medical Publishing Division; 2000. pp. 2863-913.
Raal FJ, Santos RD. Homozygous familial hypercholesterolemia: Current perspectives on diagnosis and treatment. Atherosclerosis 2012; 223: 262-8.
Risk of fatal coronary heart disease in familial hypercholesterolaemia. Scientific Steering Committee on behalf of the Simon Broome Register Group. BMJ1991; 303: 893-6.
Williams RR, Hunt SC, Schumacher MC, et al. Diagnosing heterozygous familial hypercholesterolemia using new practical criteria validated by molecular genetics. Am J Cardiol1993; 72: 171-6.
Civeira F; International Panel on Management of Familial Hypercholesterolemia. Guidelines for the diagnosis and management of heterozygous familial hypercholesterolemia. Atherosclerosis 2004; 173: 55-68.
Daniels SR, Gidding SS, de Ferranti SD; National Lipid Association Expert Panel on Familial Hypercholesterolemia. Pediatric aspects of familial hypercholesterolemias: Recommendations from the National Lipid Association Expert Panel on Familial Hypercholesterolemia. J Clin Lipidol 2011; 5 (3Suppl): S30-7.
Descamps OS, Tenoutasse S, Stephenne X, et al. Management of familial hypercholesterolemia in children and young adults: Consensus paper developed by a panel of lipidologists, cardiologists, paediatricians, nutritionists, gastroenterologists, general practitioners and a patient organization. Atherosclerosis 2011; 218: 272-80.
Stein EA, Marais AD, Szamosi T, et al. Colesevelam hydrochloride: Efficacy and safety in pediatric subjects with heterozygous familial hypercholesterolemia. J Pediatr 2010; 156: 231-6. e1-3.
Lughetti L, Bruzzi P, Predieri B. Evaluation and management of hyperlipidemia in children and adolescents. Curr Opin Pediatr 2010; 22: 485-93.
Kastelein JJP, Akdim F, Stroes ES, et al. Simvastatin with or without ezetimibe in familial hypercholesterolemia. N Engl J Med2008; 358: 1431-43.
Rossebø AB, Pedersen TR, Boman K, et al.; SEAS Investigators. Intensive lipid lowering with simvastatin and ezetimibe in aortic stenosis. N Engl J Med 2008; 359: 1343-56.
Cuchel M, Bloedon LT, Szapary PO, et al. Inhibition of microsomal triglyceride transfer protein in familial hypercholesterolemia. N EnglJ Med 2007; 356: 148-56.
Stein EA, Dufour R, Gagne C, et al. Apolipoprotein B synthesis inhibition with mipomersen in heterozygous familial hypercholesterolemia: Results of a randomized, double blind, placebo-controlled trial to assess efficacy and safety as add-on therapy in patients with coronary artery disease. Circulation 2012; 126: 2283-92.
Abifadel M, Varret M, Rab`es J-P, et al. 2003. Mutations in PCSK9 cause autosomal dominant hypercholesterolemia. Nat. Genet. 34 (2): 154–56.
Ray KK, Landmesser U, Leiter LA, et al. 2017. Inclisiran in patients at high cardiovascular risk with elevated LDL cholesterol. N. Engl. J. Med. 376 (15): 1430–40.
Pinkosky SL, Newton RS, Day EA, et al. 2016. Liver-specific ATP-citrate lyase inhibition by bempedoic acid decreases LDL-C and attenuates atherosclerosis. Nat. Commun. 7: 13457.
Tall AR, Rader DJ. 2017. The trials and tribulations of CETP inhibitors. Circ. Res. In press.
Dewey FE, Gusarova V, Dunbar RL, et al. 2017. Genetic and pharmacologic inactivation of ANGPTL3and cardiovascular disease. N. Engl. J. Med. 377 (3): 211–21.
Bisgaier CL, Essenburg AD, Barnett BC, et al. 1998. A novel compound that elevates high density lipoprotein and activates the peroxisome proliferator activated receptor. J. Lipid Res. 39 (1): 17–30.
Ajufo E, Cuchel M. 2016. Recent developments in gene therapy for homozygous familial hypercholesterolemia. Curr. Atheroscler. Rep. 18 (5): 22
Thompson GR; HEART-UK LDL Apheresis Working Group. Recommendations for the use of LDL apheresis. Atherosclerosis 2008; 198: 247-55.
Küçükkartallar T, Yankol Y, Kanmaz T, et al. Liver transplantation as a treatment option for three siblings with homozygous familial hypercholesterolemia. Pediatr Transplant2011; 15: 281-4.
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