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Familial hypercholesterolemia in adults: Treatment

Authors
Robert S Rosenson, MD
Paul Durrington, MD
Section Editor
Mason W Freeman, MD
Deputy Editor
Gordon M Saperia, MD, FACC

INTRODUCTION

Familial hypercholesterolemia (FH) is the most common autosomal dominant genetic disease. The clinical syndrome (phenotype) is characterized by extremely elevated levels of low density lipoprotein cholesterol (LDL-C) and a propensity to early onset atherosclerotic cardiovascular disease. In general, homozygotes manifest the disease at a much earlier age than heterozygotes and the disease is more severe.

This topic will focus on the primary goal of therapy in FH adults: to significantly lower LDL-C levels. Other issues regarding FH in adults are presented separately. (See "Familial hypercholesterolemia in adults: Overview".)

The management of children and adolescents with heterozygous or homozygous FH is discussed separately. (See "Dyslipidemia in children: Management", section on 'Familial hypercholesterolemia'.)

REFERRAL TO A LIPID SPECIALIST

All patients with a diagnosis of homozygous familial hypercholesterolemia should be referred to a lipid specialist with particular expertise in the care of these individuals. For adult heterozygote patients who have not achieved their low density lipoprotein cholesterol goal (see 'Goal of therapy' below) on statin therapy, consideration should be given to referral.

RATIONALE FOR INTENSE LDL-C LOWERING

Intense low density lipoprotein cholesterol (LDL-C) lowering in individuals with heterozygous or homozygous familial hypercholesterolemia (FH) decreases progression of angiographically demonstrated coronary artery disease and reduces cardiovascular disease events [1-4]. The magnitude of benefit has varied in these studies due to differing populations, the end point chosen, as well as the intensity and duration of treatment. Reduction in combined end points of up to 50 percent have been found.

              

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Literature review current through: Jul 2017. | This topic last updated: May 15, 2017.
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References
Top
  1. Kane JP, Malloy MJ, Ports TA, et al. Regression of coronary atherosclerosis during treatment of familial hypercholesterolemia with combined drug regimens. JAMA 1990; 264:3007.
  2. Raal FJ, Pilcher GJ, Panz VR, et al. Reduction in mortality in subjects with homozygous familial hypercholesterolemia associated with advances in lipid-lowering therapy. Circulation 2011; 124:2202.
  3. Neil A, Cooper J, Betteridge J, et al. Reductions in all-cause, cancer, and coronary mortality in statin-treated patients with heterozygous familial hypercholesterolaemia: a prospective registry study. Eur Heart J 2008; 29:2625.
  4. Versmissen J, Oosterveer DM, Yazdanpanah M, et al. Efficacy of statins in familial hypercholesterolaemia: a long term cohort study. BMJ 2008; 337:a2423.
  5. Stein EA. PCSK9: the Critical Role of Familial Hypercholesterolemia from Discovery to Benefit for all : Editorial to: "Efficacy and Safety of Alirocumab in Patients with Heterozygous Familial Hypercholesterolemia and LDL-C of 160 mg/Dl or Higher" by Henry N. Ginsberg et Al. Cardiovasc Drugs Ther 2016; 30:427.
  6. Stein EA, Honarpour N, Wasserman SM, et al. Effect of the proprotein convertase subtilisin/kexin 9 monoclonal antibody, AMG 145, in homozygous familial hypercholesterolemia. Circulation 2013; 128:2113.
  7. 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; 385:341.
  8. Smilde TJ, van Wissen S, Wollersheim H, et al. Effect of aggressive versus conventional lipid lowering on atherosclerosis progression in familial hypercholesterolaemia (ASAP): a prospective, randomised, double-blind trial. Lancet 2001; 357:577.
  9. Davidson MH, Stein EA, Dujovne CA, et al. The efficacy and six-week tolerability of simvastatin 80 and 160 mg/day. Am J Cardiol 1997; 79:38.
  10. Jones P, Kafonek S, Laurora I, Hunninghake D. Comparative dose efficacy study of atorvastatin versus simvastatin, pravastatin, lovastatin, and fluvastatin in patients with hypercholesterolemia (the CURVES study). Am J Cardiol 1998; 81:582.
  11. Stein EA, Strutt K, Southworth H, et al. Comparison of rosuvastatin versus atorvastatin in patients with heterozygous familial hypercholesterolemia. Am J Cardiol 2003; 92:1287.
  12. Perez de Isla L, Alonso R, Watts GF, et al. Attainment of LDL-Cholesterol Treatment Goals in Patients With Familial Hypercholesterolemia: 5-Year SAFEHEART Registry Follow-Up. J Am Coll Cardiol 2016; 67:1278.
  13. 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; 9:240.
  14. Kastelein JJ, Akdim F, Stroes ES, et al. Simvastatin with or without ezetimibe in familial hypercholesterolemia. N Engl J Med 2008; 358:1431.
  15. Aji W, Ravalli S, Szabolcs M, et al. L-arginine prevents xanthoma development and inhibits atherosclerosis in LDL receptor knockout mice. Circulation 1997; 95:430.
  16. Cuchel M, Bloedon LT, Szapary PO, et al. Inhibition of microsomal triglyceride transfer protein in familial hypercholesterolemia. N Engl J Med 2007; 356:148.
  17. Illingworth DR, Stein EA, Mitchel YB, et al. Comparative effects of lovastatin and niacin in primary hypercholesterolemia. A prospective trial. Arch Intern Med 1994; 154:1586.
  18. Yamamoto A, Matsuzawa Y, Yokoyama S, et al. Effects of probucol on xanthomata regression in familial hypercholesterolemia. Am J Cardiol 1986; 57:29H.
  19. http://www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_events/news/2015/07/news_detail_002377.jsp&mid=WC0b01ac058004d5c1.
  20. http://www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_events/news/2015/05/news_detail_002336.jsp&mid=WC0b01ac058004d5c1.
  21. Carroll C, Tappenden P, Rafia R, et al. Evolocumab for Treating Primary Hypercholesterolaemia and Mixed Dyslipidaemia: An Evidence Review Group Perspective of a NICE Single Technology Appraisal. Pharmacoeconomics 2017; 35:537.
  22. Kastelein JJ, Ginsberg HN, Langslet G, et al. ODYSSEY FH I and FH II: 78 week results with alirocumab treatment in 735 patients with heterozygous familial hypercholesterolaemia. Eur Heart J 2015; 36:2996.
  23. Moriarty PM, Parhofer KG, Babirak SP, et al. Alirocumab in patients with heterozygous familial hypercholesterolaemia undergoing lipoprotein apheresis: the ODYSSEY ESCAPE trial. Eur Heart J 2016; 37:3588.
  24. Wang A, Richhariya A, Gandra SR, et al. Systematic Review of Low-Density Lipoprotein Cholesterol Apheresis for the Treatment of Familial Hypercholesterolemia. J Am Heart Assoc 2016; 5.
  25. Thorogood M, Seed M, De Mott K, Guideline Development Group. Management of fertility in women with familial hypercholesterolaemia: summary of NICE guidance. BJOG 2009; 116:478.
  26. www.nice3.org.uk/nicemedia/pdf/CG071FullGuideline.pdf (Accessed on March 18, 2009).
  27. Toleikyte I, Retterstøl K, Leren TP, Iversen PO. Pregnancy outcomes in familial hypercholesterolemia: a registry-based study. Circulation 2011; 124:1606.
  28. Stone NJ, Robinson JG, Lichtenstein AH, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2014; 63:2889.
  29. Writing Committee, Lloyd-Jones DM, Morris PB, et al. 2016 ACC Expert Consensus Decision Pathway on the Role of Non-Statin Therapies for LDL-Cholesterol Lowering in the Management of Atherosclerotic Cardiovascular Disease Risk: A Report of the American College of Cardiology Task Force on Clinical Expert Consensus Documents. J Am Coll Cardiol 2016; 68:92.
  30. Catapano AL, Graham I, De Backer G, et al. 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias. Eur Heart J 2016; 37:2999.
  31. Landmesser U, John Chapman M, Farnier M, et al. European Society of Cardiology/European Atherosclerosis Society Task Force consensus statement on proprotein convertase subtilisin/kexin type 9 inhibitors: practical guidance for use in patients at very high cardiovascular risk. Eur Heart J 2016.
  32. Goldberg AC, Hopkins PN, Toth PP, et al. Familial hypercholesterolemia: screening, diagnosis and management of pediatric and adult patients: clinical guidance from the National Lipid Association Expert Panel on Familial Hypercholesterolemia. J Clin Lipidol 2011; 5:133.
  33. https://www.nice.org.uk/guidance/ta394/history.