Keywords
Dyslipidemias
LDL-Cholesterol
Hypercholesterolemia
How to Cite
Abstract
Introduction: Familial hypercholesterolemia (FH) is an autosomal dominant disease caused by mutations in the gene that codes for the low-density cholesterol receptor (LDLR) or in molecules associated with its function. The heterozygous form (HeFH) occurs with a prevalence of 1 in 200 to 300 people, with elevations in low-density cholesterol (LDL-C) between 160 and 580 mg / dL and an increased risk of early cardiovascular disease. Diagnosis requires scoring scales such as the Simon Broome or Dutch Lipid Clinic Network and confirmation through genetic diagnostic tests. Lifestyle modification and statins are the first-line therapy, however, it is common that the goal of LDL-C reduction is not reached or drug intolerance is present; in these cases, the use of inhibitors the proprotein convertase subtilisin-kexin type 9 (PCSK9) is recommended.
Objective: To describe the use of lomitapide in heterozygous familial hypercholesterolemia.
Case presentation: We present the case of a 68-year-old woman with HeFH who presented intolerance to statins and did not respond to PCSK9 inhibitors. Lomitapide was started, with a 50% reduction in LDL-C and adequate tolerance. This medication is approved for the treatment of homozygous familial hypercholesterolemia (HoFH) (15).
Discussion and conclusion: HeFH is associated with cardiovascular complications and mortality. In our case, statin therapy was not continued
due to intolerance, she did not respond to management with evolocumab and alirocumab either. Lomitapide is a microsomal triglyceride transfer protein (MTP) inhibitor approved for HoFH, it reduces LDL-C independent of LDLR, reaching up to 50%. There is no literature
supporting the use of lomitapide in patients with simple HeFH, as in our patient. Thus, lomitapide may be indicated as an alternative in patients with HeFH.
References
Schmidt EB, Hedegaard BS, Retterstøl K. Familial hypercholesterolaemia: history, diagnosis, screening, management and challenges. Heart. 2020;106(24):1940-1946. doi:10.1136/heartjnl-2019-316276
Benito-Vicente A, Uribe KB, Jebari S, Galicia-Garcia U, Ostolaza H, Martin C. Familial Hypercholesterolemia: The Most Frequent Cholesterol Metabolism Disorder Caused Disease. Int J Mol Sci. 2018;19(11):3426. Published 2018 Nov 1. doi:10.3390/ijms19113426
Shah NP, Ahmed HM, Wilson Tang WH. Familial hypercholesterolemia: Detect, treat, and ask about family [published correction appears in Cleve Clin J Med. 2020 May;87(5):311]. Cleve Clin J Med. 2020;87(2):109-120. doi:10.3949/ccjm.87a.19021
Mikhailova S, Ivanoshchuk D, Timoshchenko O, Shakhtshneider E. Genes Potentially Associated with Familial Hypercholesterolemia. Biomolecules. 2019;9(12):807. Published 2019 Nov 29. doi:10.3390/biom9120807
Moldovan V, Banescu C, Dobreanu M. Molecular diagnosis methods in familial hypercholesterolemia. Anatol J Cardiol. 2020;23(3):120-127. doi:10.14744/AnatolJCardiol.2019.95038
Mach F, Baigent C, Catapano AL, et al. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk [published correction appears in Eur Heart J. 2020 Nov 21;41(44):4255]. Eur Heart J. 2020;41(1):111-188. doi:10.1093/eurheartj/ehz455
McGowan MP, Hosseini Dehkordi SH, Moriarty PM, Duell PB. Diagnosis and Treatment of Heterozygous Familial Hypercholesterolemia. J Am Heart Assoc. 2019;8(24):e013225. doi:10.1161/JAHA.119.013225
Barkas F, Elisaf M, Milionis H. Statins decrease the risk of stroke in individuals with heterozygous familial hypercholesterolemia: A systematic review and meta-analysis. Atherosclerosis. 2015;243(1):60-64. doi:10.1016/j.atherosclerosis.2015.08.038
deGoma EM, Ahmad ZS, O'Brien EC, et al. Treatment Gaps in Adults With Heterozygous Familial Hypercholesterolemia in the United States: Data From the CASCADE-FH Registry. Circ Cardiovasc Genet. 2016;9(3):240-249. doi:10.1161/CIRCGENETICS.116.001381
Pang J, Chan DC, Watts GF. The Knowns and Unknowns of Contemporary Statin Therapy for Familial Hypercholesterolemia. Curr Atheroscler Rep. 2020;22(11):64. Published 2020 Sep 1. doi:10.1007/s11883-020-00884-2
Santos RD. Screening and management of familial hypercholesterolemia. Curr Opin Cardiol. 2019;34(5):526-530. doi:10.1097/HCO.0000000000000660
Mazidi M, Rezaie P, Karimi E, Kengne AP. The effects of bile acid sequestrants on lipid profile and blood glucose concentrations: A systematic review and meta-analysis of randomized controlled trials. Int J Cardiol. 2017;227:850-857. doi:10.1016/j.ijcard.2016.10.011
Sabatine MS, Giugliano RP, Keech AC, et al. Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease. N Engl J Med. 2017;376(18):1713-1722. doi:10.1056/NEJMoa1615664
Schwartz GG, Steg PG, Szarek M, et al. Alirocumab and Cardiovascular Outcomes after Acute Coronary Syndrome. N Engl J Med. 2018;379(22):2097-2107. doi:10.1056/NEJMoa1801174
Raal FJ, Hovingh GK, Catapano AL. Familial hypercholesterolemia treatments: Guidelines and new therapies. Atherosclerosis. 2018;277:483-492. doi:10.1016/j.atherosclerosis.2018.06.859
Polychronopoulos G, Tziomalos K. Treatment of heterozygous familial hypercholesterolemia: what does the future hold?. Expert Rev Clin Pharmacol. 2020;13(11):1229-1234. doi:10.1080/17512433.2020.1839417
Chmara M, Wasag B, Zuk M, et al. Molecular characterization of Polish patients with familial hypercholesterolemia: novel and recurrent LDLR mutations. J Appl Genet. 2010;51(1):95-106. doi:10.1007/BF03195716
Brunham LR, Ruel I, Aljenedil S, et al. Canadian Cardiovascular Society Position Statement on Familial Hypercholesterolemia: Update 2018. Can J Cardiol. 2018;34(12):1553-1563. doi:10.1016/j.cjca.2018.09.005
Raal FJ, Honarpour N, Blom DJ, et al. Inhibition of PCSK9 with evolocumab in homozygous familial hypercholesterolaemia (TESLA Part B): a randomised, double-blind, placebo-controlled trial. Lancet. 2015;385(9965):341-350. doi:10.1016/S0140-6736(14)61374-X
Raal FJ, Stein EA, Dufour R, et al. PCSK9 inhibition with evolocumab (AMG 145) in heterozygous familial hypercholesterolaemia (RUTHERFORD-2): a randomised, double-blind, placebo-controlled trial. Lancet. 2015;385(9965):331-340. doi:10.1016/S0140-6736(14)61399-4
Tomlinson B, Patil NG, Fok M, Lam CWK. Role of PCSK9 Inhibitors in Patients with Familial Hypercholesterolemia. Endocrinol Metab (Seoul). 2021;36(2):279-295. doi:10.3803/EnM.2021.964
Khoury E, Brisson D, Roy N, Tremblay G, Gaudet D. Review of the long-term safety of lomitapide: a microsomal triglycerides transfer protein inhibitor for treating homozygous familial hypercholesterolemia. Expert Opin Drug Saf. 2019;18(5):403-414. doi:10.1080/14740338.2019.1602606
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. doi:10.1016/S0140-6736(12)61731-0
Underberg JA, Cannon CP, Larrey D, Makris L, Blom D, Phillips H. Long-term safety and efficacy of lomitapide in patients with homozygous familial hypercholesterolemia: Five-year data from the Lomitapide Observational Worldwide Evaluation Registry (LOWER). J Clin Lipidol. 2020;14(6):807-817. doi:10.1016/j.jacl.2020.08.006
Alonso R, Cuevas A, Mata P. Lomitapide: a review of its clinical use, efficacy, and tolerability. Core Evid. 2019;14:19-30. Published 2019 Jul 1. doi:10.2147/CE.S174169
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
Copyright (c) 2022 Revista Endocrino