Close
New

Medscape is available in 5 Language Editions – Choose your Edition here.

 

Familial Hypercholesterolemia Medication

  • Author: Mose July, MD; Chief Editor: Romesh Khardori, MD, PhD, FACP  more...
 
Updated: Jul 10, 2016
 

Medication Summary

HMG-CoA reductase inhibitors (statins) are the medications of choice for the treatment of LDLc elevations in patients with heterozygous FH because they have the greatest efficacy and are easily tolerated and because multiple randomized, placebo-controlled trials have shown that lowering LDLc levels with statins reduces coronary morbidity and mortality and, in some cases, total mortality. The strongest statins, rosuvastatin and atorvastatin, at their maximum approved doses, can be expected to reduce LDLc levels 50-60%.[11, 47, 48, 49, 50]

The ATPIII update advises that the starting dose of a statin be sufficient to lower the LDLc 30-40% (see Table 3).[8]

Even the maximum doses of the strongest statins are usually inadequate for patients with FH, and the addition of one or more nonstatin cholesterol-lowering medications is necessary. PCSK9 inhibitors are now available in the United States to add to maximally tolerated statins for patients with HeFH.

Bile acid sequestrants (eg, cholestyramine, colestipol, colesevelam) can be added with no risk of drug interaction, with the exception of absorption of the statin (and many other medications) if taken at the same time. Bile acid sequestrants modestly decrease LDLc levels with a small increase in HDLc and triglyceride levels. Other medications should be taken 1 hour before or 4 hours after a bile acid sequestrant. Colesevelam, which is a polymer, has less gastrointestinal side effects than the older resins and is effective at a lower dose (maximum 7 tabs/d).

Nicotinic acid (niacin) not only lowers LDLc levels but also has significant HDL-raising and triglyceride-lowering effects. There are few data to support the belief that niacin increases the risk of myopathy if combined with a statin.

Fibric acid derivatives include gemfibrozil (Lopid) and fenofibrate (Tricor). Outside of the United States, bezafibrate is also available. The fibrates lower triglyceride levels and raise HDLc levels, but they do not reliably lower LDLc levels. They increase the risk of statin-induced myositis more so than niacin. Therefore, this class of drugs is not usually useful in patients with FH.

Ezetimibe reduces LDLc levels approximately 18%, with small HDLc-raising and triglyceride-lowering effects. Because the mechanism by which it inhibits cholesterol absorption is quite specific, it does not interfere with the absorption of other drugs and does not cause the constipation associated with bile acid sequestrants. This medication has a major role in LDL-lowering when a statin alone is not sufficient and can be administered as a single tablet when combined with simvastatin (Vytorin).

These statin combinations are particularly appropriate for patients with FH, most of whom will require 2 or more drugs to reach their LDLc goals. In addition, significantly greater than expected decreases in the LDLc level are frequently observed.

An extended follow-up of the Heart Protection Study examined the long-term efficacy and safety of LDLc-lowering with simvastatin treatment. In-trial cardiovascular benefits began after the first year and increased with each subsequent year of statin therapy and persisted 6 years beyond the end of the study. No difference in nonvascular morbidity or mortality was observed either during 5 years of statin therapy or in 6-year follow-up. The investigators recommend prompt initiation and long-term statin treatment in patients who are at increased risk for vascular events.[51]

In a double-blind, randomized, placebo-controlled trial, Stein et al evaluated the efficacy and safety of add-on therapy with mipomersen, an apolipoprotein B synthesis inhibitor, in 124 patients with heterozygous familial hypercholesterolemia. They found that mipomersen treatment led to further reductions in apolipoprotein B-containing lipoproteins, including lipoprotein(a) and LDL.[52]

Table 3. Statin and Statin Combination Approved Doses, Expected LDLc Decrease, and Dose Required for 30-40% LDLc Reduction (Open Table in a new window)

 



Statin



 



FDA-Approved Dose



 



Expected LDLc Decrease



 



Dose Required for 30-40% LDLc Reduction



Atorvastatin 10-80 mg daily 35-60% 10 mg
Fluvastatin 20-40 mg at bedtime 20-30% 40 mg qd/bid
40 mg bid 35% 40 mg bid
Extended-release fluvastatin



(Lescol XL)



80 mg at bedtime 35-38% 80 mg at bedtime
Lovastatin 20-80 mg at supper 25-48% 40 mg at dinner
Extended-release lovastatin



(Altoprev)



20-60 mg at bedtime 25-45% 60 mg at bedtime
Pravastatin 40-80 mg at bedtime 30-40% 40 mg at bedtime
Rosuvastatin 10-40 mg daily 40-60% 5 mg daily
Simvastatin 20-80 mg daily at bedtime 35-50% 20 mg at bedtime
Simvastatin + ezetimibe



(Vytorin)



10/20 mg



10/40 mg



10/80 mg



at bedtime



50-60% 10/20 mg at bedtime
Next

HMG-CoA reductase inhibitors (statins)

Class Summary

Statins inhibit HMG-CoA reductase, the rate-limiting enzyme in cholesterol synthesis. Reduction in hepatocyte cholesterol causes up-regulation of LDL (B,E) receptors, which, in turn, reduces plasma LDL levels. Statins are used adjunctively with diet and exercise to treat hypercholesterolemia and are the most potent LDL-lowering medications. All statins have modest triglyceride-lowering and HDL-raising effects. Randomized, double-blind, placebo-controlled trials demonstrate regression of coronary atherosclerosis but, even more importantly, reduction in rates of total mortality, coronary events, and stroke.

- Because hepatic cholesterol synthesis is greatest at night, most of the statins should be taken at bedtime. Lovastatin is better absorbed with food and is most effective taken with supper. Rosuvastatin and atorvastatin are the strongest statins because they have long half-lives.

- Atorvastatin, simvastatin, and lovastatin are metabolized by the P450 cytochrome 3A4, which is inhibited by many other drugs and may thereby increase the risk of myopathy. Rosuvastatin, fluvastatin, and pravastatin are metabolized by other pathways.

- The weaker statins (pravastatin, fluvastatin, lovastatin) do not lower LDLc levels as much and, therefore, are not the statins of choice for patients with FH. However, myopathy is dose and strength-related and thus these statins may not be as likely to cause severe myopathy.

- The Report of the National Lipid Association's Statin Safety Task Force published in the American Journal of Cardiology (Volume 97, Issue 8, Supplement 1, pages S1-S98, 17 April 2006)[53] provides the results of a rigorous, unbiased assessment of statin safety. It includes specific reports on the muscle, liver, renal, and neurologic effects of statins; as well as addressing drug interactions and other safety issues.

Atorvastatin and rosuvastatin are long-acting statins and do not require evening dosing. Simvastatin is the third strongest statin and should be administered at bedtime. The three weaker statins (pravastatin, fluvastatin, lovastatin) are not the statins of choice for patients with FH. Rosuvastatin, unlike atorvastatin and simvastatin is not metabolized by the cytochrome 3A4; and, therefore, may have fewer drug interactions.

Atorvastatin (Lipitor)

 

Second strongest LDL-lowering statin approved to date. Long half-life. Clinical trial has shown reduction in CHD events.

As an adjunct to diet, approved indications are to reduce total cholesterol, LDLc, triglycerides, and apoB; increase HDLc in patients with primary hypercholesterolemia (HeFH and nonfamilial) and mixed dyslipidemia (Fredrickson types IIa and IIb); decrease triglycerides in patients with type IV; and treat patients with type III dysbetalipoproteinemia.

It is approved for treatment of adults with homozygous FH as an adjunct to other LDL-lowering measures (eg, LDL apheresis) or if other treatments are not available.

It is approved for children and adolescents aged ≥10 y if after an adequate trial of diet, LDLc remains ≥190 mg/dL, or if LDLc remains ≥160 mg/dL and there is a positive family history of premature CVD or the patient has >2 other CVD risk factors.

Simvastatin (Zocor)

 

Third strongest LDL-lowering drug approved to date. Several randomized clinical trials in patients with and without CHD have shown clinically significant reductions in CHD morbidity and mortality rates and, in some cases, total mortality rates.

In addition to its multiple effects in improving lipid profiles (decrease in total cholesterol, LDLc, triglycerides, and apoB and increase in HDLc), has been approved in adults for homozygous FH and heterozygous FH, for reducing risk of total mortality by reducing CHD death, reducing risk of nonfatal MI and stroke, reducing need for coronary and noncoronary revascularization procedures, and for adolescents with heterozygous FH.

Rosuvastatin (Crestor)

 

Rosuvastatin has the strongest lipid-lowering potential of all the statins currently available. It is indicated for adults with primary hyperlipidemia and mixed dyslipidemia, homozygous FH, primary dysbetalipoproteinemia, and hypertriglyceridemia. In children and adolescents, it is indicated for homozygous FH and heterozygous FH.

Pitavastatin (Livalo)

 

HMG-CoA reductase inhibitor (statin) indicated for primary or mixed hyperlipidemia in adults. In clinical trials, 2 mg/d reduced total cholesterol and LDL cholesterol similar to atorvastatin 10 mg/d and simvastatin 20 mg/d.

Pravastatin (Pravachol)

 

Pravastatin is indicated for heterozygous FH in children and adolescents aged ≥8 y if after an adequate trial of diet, LDLc remains ≥190 mg/dL, or if LDLc remains ≥160 mg/dL and there is a positive family history of premature CVD or the patient has >2 other CVD risk factors.

Lovastatin (Altoprev, Mevacor)

 

Lovastatin is indicated for heterozygous FH in adults and in children and adolescents aged ≥10 y if after an adequate trial of diet, LDLc remains ≥190 mg/dL, or if LDLc remains ≥160 mg/dL and there is a positive family history of premature CVD or the patient has >2 other CVD risk factors.

Fluvastatin (Lescol, Lescol XL)

 

Fluvastatin is indicated for heterozygous FH in adults and in children and adolescents aged ≥10 y if after an adequate trial of diet, LDLc remains ≥190 mg/dL, or if LDLc remains ≥160 mg/dL and there is a positive family history of premature CVD or the patient has >2 other CVD risk factors.

Previous
Next

Vitamins

Class Summary

Niacin at doses of at least 1-1.5 g/d lowers LDLc levels 10-25%. HDLc levels can increase substantially, 30% or more, particularly at higher doses. Triglyceride levels decrease approximately 50%. Niacin, whether OTC or by prescription, costs less than any other lipid-lowering medication. For reasons not clearly understood, changing brands during treatment is more likely to cause hepatotoxicity, more so with time-release niacin than with regular niacin, particularly at a dose of 3 g/d or more. Nicotinamide, while acceptable treatment for vitamin B-3 deficiency, does not affect lipid levels, nor do most of the "no flush" niacin preparations, including inositol hexaniacinate.

On April 15, 2016, the FDA announced that it was withdrawing approval for the new drug applications (NDAs) for the use of niacin ER with statins. The action stemmed from the results of several large cardiovascular outcome trials, including AIM-HIGH, ACCORD, and HPS2-THRIVE, with the FDA determining that "scientific evidence no longer supports the conclusion that a drug-induced reduction in triglyceride levels and/or increase in HDL-cholesterol levels in statin-treated patients results in a reduction in the risk of cardiovascular events."[54]

Immediate-release niacin/vitamin B-3 (nicotinic acid, Niacor, Nicolar)

 

Less hepatotoxic than SR niacin but not as well tolerated by patients because of prostaglandin-mediated flushing, itching, or rash. IR niacin started at low doses and gradually increased over several wk allows some patients to accommodate to these adverse effects.

Higher doses (4-6 g/d) can be used more safely than those of SR niacin.

Niacor and Nicolar are prescription formulations of IR niacin that, while more expensive than OTC brands, may decrease likelihood of patient switching brands. Changing formulation of niacin while on high doses may increase risk of hepatotoxicity.

SR niacin (Slo-Niacin, Niaspan)

 

More hepatotoxic than IR niacin; therefore, strongly advise against switching formulations or brands during treatment. Both OTC and prescription SR niacin is available. OTC brands cost less, but if using this option, only recommend reliable manufacturers.

Slo-Niacin is an OTC formulation available in 250-, 500-, and 750-mg tabs. Sundown also manufactures OTC SR niacin. Prescription SR niacin, Niaspan, is available in 375-, 500-, and 1000-mg tabs.

Previous
Next

Bile acid sequestrants (resins)

Class Summary

Anion-exchange compounds that work by preventing reabsorption of bile in the intestine. Modestly lower LDLc and increase HDLc levels but can raise triglyceride levels. When used with a statin, the LDLc-lowering effects are additive. Not absorbed systemically and, therefore, are safer than most medications. Powder should never be taken in dry form. Combine with water, other noncarbonated fluid, or soft food (eg, applesauce, soup). Probably more effective at mealtime. Colestipol is formulated both as a powder and a tablet; however, 1 tablet contains only 1 g of colestipol. Given that the maximum dose of colestipol powder is 30 g, taking an even 10 tablets (which most patients will object to) will have only minimal LDL-lowering impact.

Because resins can decrease absorption of many other medications, those medications should be taken 1 h before or 4 h after the resin. Major adverse effect is constipation, and patient compliance is often an issue.

WelChol is a polymer (not a resin) and is the newest bile acid sequestrant to enter the market. It is formulated as a tablet, and the maximum number is 7 tab/d, which may improve compliance. Reportedly causes fewer adverse GI effects and fewer drug interactions. Added to a statin, further LDLc reductions of as much as 20% can be expected.

Cholestyramine (Questran)

 

Orange-flavored and sweetened with either sucrose (Questran) or aspartame (Questran Light). Must be mixed with fluids or soft, high-moisture foods.

Forms a nonabsorbable complex with bile acids in the intestine, which, in turn, inhibits enterohepatic reuptake of intestinal bile salts.

Safer than most medications.

Colestipol (Colestid)

 

Formulated as dry, flavorless powder and as a tab. Otherwise, similar to cholestyramine. Because contains no flavoring or sweeteners, can be mixed with a wider variety of liquid foods (eg, soup, tomato juice).

Colesevelam (WelChol)

 

Better tolerated than older agents (eg, cholestyramine, colestipol), and drug interactions are less of a problem. Can lower LDLc 15-18% as monotherapy. Useful in patients who cannot tolerate statins, who have contraindications for statin therapy, or who request nonsystemic therapy. Can also be used in combination with a statin for additive LDLc lowering. Has no effect on serum triglycerides or beneficial effects on HDLc. Available in a 643-mg tab.

Previous
Next

Lipid-Lowering Agents, Other

Class Summary

A variety of agents are emerging on the market as adjuncts to existing drugs and other therapies.

Lomitapide (Juxtapid)

 

Lomitapide directly binds and inhibits microsomal triglyceride transfer protein (MTP), which resides in the lumen of the endoplasmic reticulum, thereby preventing apo B-containing lipoproteins assembly in enterocytes and hepatocytes. This inhibits the synthesis of chylomicrons and VLDL; inhibition of VLDL synthesis leads to reduced LDL-C plasma levels. This agent is indicated as an adjunct to a low-fat diet and other lipid lowering treatments, including LDL apheresis where available, to reduce LDL-C, TC, apo B, and non-HDL-C in patients with homozygous familial hypercholesterolemia.

Mipomersen (Kynamro)

 

Mipomersen is an antisense oligonucleotide inhibitor that targets mRNA for apolipoprotein B-100, the principal apolipoprotein of LDL and its metabolic precursor, VLDL. It is indicated as an adjunct to lipid-lowering medications and diet to reduce LDL-C, apoB, TC, and non-HDL-C in patients with homozygous familial hypercholesterolemia (HoFH). Safety and effectiveness as an adjunct to LDL apheresis have not been established.

Ezetimibe (Zetia)

 

First in a new class of cholesterol-lowering agents. Inhibits cholesterol intestinal absorption. Approved as monotherapy or in combination with HMG-CoA reductase inhibitors.

Previous
Next

PCSK9 Inhibitors

Class Summary

Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors decrease LDLR degradation by PCSK9, and thereby improve LDL-C clearance and lower plasma LDL-C.

Alirocumab (Praluent)

 

Alirocumab is a monoclonal antibody that binds to PCSK9. LDL-C is cleared from the circulation preferentially through the LDL receptor (LDLR) pathway. PCSK9 is a serine protease that destroys LDLR in the liver resulting in decreased LDL-C clearance and increased plasma LDL-C. PCSK9 inhibitors decrease LDLR degradation by PCSK9. It is indicated as adjunct to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia (HeFH) or clinical atherosclerotic cardiovascular disease, who require additional lowering of LDL-C.

Evolocumab (Repatha)

 

Evolocumab is a monoclonal antibody that inhibits the serine protease PCSK9. PCSK9 destroys the LDL receptor in the liver; therefore, decreasing LDL-C clearance. It is indicated as an adjunct to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia (HeFH) or clinical atherosclerotic CVD, who require additional lowering of LDL-C. Evolocumab is also indicated as an adjunct to diet and other LDL-lowering therapies (eg, statins, ezetimibe, LDL apheresis) for the treatment of adults and adolescents aged 13-17 y with homozygous familial hypercholesterolemia (HoFH) who require additional lowering of LDL-C.

Previous
 
 
Contributor Information and Disclosures
Author

Mose July, MD Fellow in Endocrinology, Diabetes and Metabolism, Marshall University School of Medicine

Mose July, MD is a member of the following medical societies: American Association of Clinical Endocrinologists, Endocrine Society

Disclosure: Nothing to disclose.

Coauthor(s)

Omolola Bolaji Olajide, MD, FACE Associate Professor, Consultant, Department of Internal Medicine, Program Director, Fellowship Program, Section of Endocrinology, Joan C Edwards School of Medicine at Marshall University

Omolola Bolaji Olajide, MD, FACE is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Physicians, Endocrine Society, International Society for Clinical Densitometry

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Yoram Shenker, MD Chief of Endocrinology Section, Veterans Affairs Medical Center of Madison; Interim Chief, Associate Professor, Department of Internal Medicine, Section of Endocrinology, Diabetes and Metabolism, University of Wisconsin at Madison

Yoram Shenker, MD is a member of the following medical societies: American Heart Association, Central Society for Clinical and Translational Research, Endocrine Society

Disclosure: Nothing to disclose.

Chief Editor

Romesh Khardori, MD, PhD, FACP Professor of Endocrinology, Director of Training Program, Division of Endocrinology, Diabetes and Metabolism, Strelitz Diabetes and Endocrine Disorders Institute, Department of Internal Medicine, Eastern Virginia Medical School

Romesh Khardori, MD, PhD, FACP is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Physicians, American Diabetes Association, Endocrine Society

Disclosure: Nothing to disclose.

Additional Contributors

Gregory William Rutecki, MD Professor of Medicine, Fellow of The Center for Bioethics and Human Dignity, University of South Alabama College of Medicine

Gregory William Rutecki, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American Society of Nephrology, National Kidney Foundation, Society of General Internal Medicine

Disclosure: Nothing to disclose.

References
  1. Illingworth DR, Duell PB, Connor WE. Disorders of lipid metabolism. Felig P, Baxter JD, Frohmin LA, eds. Endocrinology and Metabolism. 1315-1403.

  2. Ueda M. Familial hypercholesterolemia. Mol Genet Metab. 2005 Dec. 86(4):423-6. [Medline].

  3. Marks D, Thorogood M, Neil HA, Humphries SE. A review on the diagnosis, natural history, and treatment of familial hypercholesterolaemia. Atherosclerosis. 2003 May. 168(1):1-14. [Medline].

  4. Wood S. New EAS Consensus Document Tackles Familial Hypercholesterolemia. Medscape Medical News. Available at http://www.medscape.com/viewarticle/805252. Accessed: September 5, 2013.

  5. Nordestgaard BG, Chapman MJ, Humphries SE, Ginsberg HN, Masana L, Descamps OS, et al. Familial hypercholesterolaemia is underdiagnosed and undertreated in the general population: guidance for clinicians to prevent coronary heart disease: Consensus Statement of the European Atherosclerosis Society. Eur Heart J. 2013 Aug 15. [Medline].

  6. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III). JAMA. 2001 May 16. 285(19):2486-97. [Medline].

  7. National Cholesterol Education Program Expert Panel. Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. The Expert Panel. Arch Intern Med. 1988 Jan. 148(1):36-69. [Medline].

  8. Grundy SM, Cleeman JI, Merz CN, Brewer HB Jr, Clark LT, Hunninghake DB, et al. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation. 2004 Jul 13. 110(2):227-39. [Medline].

  9. Connor WE, Connor SL. Dietary treatment of familial hypercholesterolemia. Arteriosclerosis. 1989 Jan-Feb. 9(1 Suppl):I91-105. [Medline].

  10. Illingworth DR. Management of hypercholesterolemia. Med Clin North Am. 2000 Jan. 84(1):23-42. [Medline].

  11. Brown BG, Zhao XQ, Chait A, Fisher LD, Cheung MC, Morse JS. Simvastatin and niacin, antioxidant vitamins, or the combination for the prevention of coronary disease. N Engl J Med. 2001 Nov 29. 345(22):1583-92. [Medline].

  12. Toklu B, Amirian J, Giugliano RP. Current indications, cost, and clinical use of anti-PCSK9 monoclonal antibodies. American College of Cardiology. Available at http://www.acc.org/latest-in-cardiology/articles/2016/05/18/14/34/current-indications-cost-and-clinical-use-of-anti-pcsk9-monoclonal-antibodies. May 19, 2016; Accessed: July 10, 2016.

  13. Wiegman A et al. Familial hypercholesterolaemia in children and adolescents: gaining decades of life by optimizing detection and treatment. Eur Heart J. 2015 Sep 21. 36 (36):2425-37. [Medline]. [Full Text].

  14. Austin MA, Hutter CM, Zimmern RL, Humphries SE. Familial hypercholesterolemia and coronary heart disease: a HuGE association review. Am J Epidemiol. 2004 Sep 1. 160(5):421-9. [Medline].

  15. Sibley C, Stone NJ. Familial hypercholesterolemia: a challenge of diagnosis and therapy. Cleve Clin J Med. 2006 Jan. 73(1):57-64. [Medline].

  16. Bjorkhem I, Boberg KM. Inborn errors in bile acid biosynthesis and storage of sterols other than cholesterol. Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The Metabolic and Molecular Bases of Inherited Disease. 8th ed. New York, NY: McGraw-Hill; 2001. 2073-2099.

  17. Garcia CK, Wilund K, Arca M, Zuliani G, Fellin R, Maioli M, et al. Autosomal recessive hypercholesterolemia caused by mutations in a putative LDL receptor adaptor protein. Science. 2001 May 18. 292(5520):1394-8. [Medline].

  18. Kane JP, Havel RJ. Disorders of the biogenesis and secretion of lipoproteins containing the B apolipoproteins. Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The Metabolic and Molecular Bases of Inherited Disease. 8th ed. New York, NY: McGraw-Hill; 2001. 2717-2752.

  19. Goldstein JL, Brown MS. Regulation of low-density lipoprotein receptors: implications for pathogenesis and therapy of hypercholesterolemia and atherosclerosis. Circulation. 1987 Sep. 76(3):504-7. [Medline].

  20. Goldstein JL, Brown MS. Molecular medicine. The cholesterol quartet. Science. 2001 May 18. 292(5520):1310-2. [Medline].

  21. Hammond E, Watts GF, Rubinstein Y, et al. Role of international registries in enhancing the care of familial hypercholesterolaemia. Int J Evid Based Healthc. 2013 Jun. 11(2):134-9. [Medline]. [Full Text].

  22. de Ferranti SD, Rodday AM, Mendelson MM, Wong JB, Leslie LK, Sheldrick RC. Prevalence of Familial Hypercholesterolemia in the 1999 to 2012 United States National Health and Nutrition Examination Surveys (NHANES). Circulation. 2016 Mar 15. 133 (11):1067-72. [Medline].

  23. Khachadurian AK, Uthman SM. Experiences with the homozygous cases of familial hypercholesterolemia. A report of 52 patients. Nutr Metab. 1973. 15(1):132-40. [Medline].

  24. Pisciotta L, Priore Oliva C, Pes GM, Di Scala L, Bellocchio A, Fresa R, et al. Autosomal recessive hypercholesterolemia (ARH) and homozygous familial hypercholesterolemia (FH): a phenotypic comparison. Atherosclerosis. 2006 Oct. 188(2):398-405. [Medline].

  25. Williams RR, Hunt SC, Schumacher MC, et al. Diagnosing heterozygous familial hypercholesterolemia using new practical criteria validated by molecular genetics. Am J Cardiol. 1993 Jul 15. 72(2):171-6. [Medline].

  26. Patel MD, Thompson PD. Phytosterols and vascular disease. Atherosclerosis. 2006 May. 186(1):12-9.

  27. [Guideline] Catapano AL, Reiner Z, De Backer G, et al. ESC/EAS Guidelines for the management of dyslipidaemias The Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS). Atherosclerosis. 2011 Jul. 217(1):3-46. [Medline].

  28. [Guideline] 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 Jul 1. 63 (25 Pt B):2889-934. [Medline]. [Full Text].

  29. European Atherosclerosis Society. New EAS Consensus Panel Statement on Homozygous FH. Available at http://www.eas-society.org/02-2014---consensus-on-homozygous-fh.aspx. Accessed: August 8, 2014.

  30. FDA Approves Atorvastatin/Ezetimibe Combo Tablet. Medscape. May 3 2013. [Full Text].

  31. Richter WO, Donner MG, Hofling B, Schwandt P. Long-term effect of low-density lipoprotein apheresis on plasma lipoproteins and coronary heart disease in native vessels and coronary bypass in severe heterozygous familial hypercholesterolemia. Metabolism. 47(7):863-8. [Medline].

  32. Thompsen J, Thompson PD. A systematic review of LDL apheresis in the treatment of cardiovascular disease. Atherosclerosis. 2006 Mar 16. [Epub ahead of print].

  33. Sabatine MS, Giugliano RP, Wiviott SD, Raal FJ, Blom DJ, Robinson J, et al. Efficacy and safety of evolocumab in reducing lipids and cardiovascular events. N Engl J Med. 2015 Apr 16. 372 (16):1500-9. [Medline].

  34. Koren MJ, Giugliano RP, Raal FJ, Sullivan D, Bolognese M, Langslet G, et al. Efficacy and safety of longer-term administration of evolocumab (AMG 145) in patients with hypercholesterolemia: 52-week results from the Open-Label Study of Long-Term Evaluation Against LDL-C (OSLER) randomized trial. Circulation. 2014 Jan 14. 129 (2):234-43. [Medline]. [Full Text].

  35. Langslet G, Emery M, Wasserman SM. Evolocumab (AMG 145) for primary hypercholesterolemia. Expert Rev Cardiovasc Ther. 2015 May. 13 (5):477-88. [Medline].

  36. Cuchel M, Meagher EA, du Toit Theron H, Blom DJ, Marais AD, Hegele RA, 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. 2012 Nov 1. [Medline].

  37. Nainggolan L. Mipomersen Approved in US for Homozygous FH. Available at http://www.medscape.com/viewarticle/778465. Accessed: February 12, 2013.

  38. Raal FJ, Santos RD, Blom DJ, Marais AD, Charng MJ, Cromwell WC, et al. Mipomersen, an apolipoprotein B synthesis inhibitor, for lowering of LDL cholesterol concentrations in patients with homozygous familial hypercholesterolaemia: a randomised, double-blind, placebo-controlled trial. Lancet. 2010 Mar 20. 375(9719):998-1006. [Medline].

  39. Kane JP, Malloy MJ, Tun P, Phillips NR, Freedman DD, Williams ML, et al. Normalization of low-density-lipoprotein levels in heterozygous familial hypercholesterolemia with a combined drug regimen. N Engl J Med. 1981 Jan 29. 304(5):251-8. [Medline].

  40. Preiss D, Seshasai SR, Welsh P, et al. Risk of incident diabetes with intensive-dose compared with moderate-dose statin therapy: a meta-analysis. JAMA. 2011 Jun 22. 305(24):2556-64. [Medline].

  41. ODYSSEY outcomes: Evaluation of cardiovascular outcomes after an acute coronary syndrome during treatment with alirocumab SAR236553 (REGN727). ClinicalTrials.gov. NCT01663402. ClinicalTrials.gov. Available at https://clinicaltrials.gov/ct2/show/NCT01663402. 2015 Jul 10; Accessed: July 27, 2015.

  42. Robinson JG, Farnier M, Krempf M, Bergeron J, Luc G, Averna M, et al. Efficacy and safety of alirocumab in reducing lipids and cardiovascular events. N Engl J Med. 2015 Apr 16. 372 (16):1489-99. [Medline].

  43. Kereiakes DJ, Robinson JG, Cannon CP, Lorenzato C, Pordy R, Chaudhari U, et al. Efficacy and safety of the proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab among high cardiovascular risk patients on maximally tolerated statin therapy: The ODYSSEY COMBO I study. Am Heart J. 2015 Jun. 169 (6):906-915.e13. [Medline]. [Full Text].

  44. O'Riordan M. Rosuvastatin slows atherosclerosis in FH kids. Heartwire. June 6, 2014. [Full Text].

  45. Braamskamp M, Langslet G, McCrindle BW, et al. Efficacy and safety of rosuvastatin in children aged 6–17 years with familial hypercholesterolemia: findings from the CHARON study (abstract M140). Presented at EAS 2014: The 82nd European Atherosclerosis Society Congress; June 2, 2014; Madrid, Spain.

  46. Braamskamp MJAM, Langslet G, McCrindle BW, et al. Effect of rosuvastatin therapy on carotid intima media thickness in children with familial hypercholesterolemia: findings from the CHARON study. Presented at EAS 2014: The 82nd European Atherosclerosis Society Congress; June 3, 2014; Madrid, Spain.

  47. Cohen DE, Anania FA, Chalasani N,. An assessment of statin safety by hepatologists. Am J Cardiol. 2006 Apr 17. 97(8A):77C-81C. [Medline].

  48. Scandinavian Simvastatin Survival Study. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet. 1994 Nov 19. 344(8934):1383-9. [Medline].

  49. Jones PH, Davidson MH, Stein EA. Comparison of the efficacy and safety of rosuvastatin versus atorvastatin, simvastatin, and pravastatin across doses (STELLAR* Trial). Am J Cardiol. 2003 Jul 15. 92(2):152-60. [Medline].

  50. Thompson PD, Clarkson PM, Rosenson RS, National Lipid Association Statin Safety Task Force Liver Exert Panel. An assessment of statin safety by muscle experts. Am J Cardiol. 2006 Apr 17. 97(8A):69C-76C.

  51. Bulbulia R, Bowman L, Wallendszus K, et al. Effects on 11-year mortality and morbidity of lowering LDL cholesterol with simvastatin for about 5 years in 20,536 high-risk individuals: a randomised controlled trial. Lancet. 2011 Dec 10. 378(9808):2013-20. [Medline]. [Full Text].

  52. Stein EA, Dufour R, Gagne C, Gaudet D, East C, Donovan JM, 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 Oct 11. [Medline].

  53. McKenney JM, Davidson MH, Jacobson TA, Guyton JR, National Lipid Association Statin Safety Task Force Liver Expert Panel. Final conclusions and recommendations of the National Lipid Association Statin Safety Assessment Task Force. Am J Cardiol. 2006 Apr 17. 97(8A):89C-94C.

  54. Wending P. FDA pulls approval of niacin, fibrate in combo with statins. Heartwire. 2016 Apr 15. Available at http://www.medscape.com/viewarticle/862022.

  55. Amundsen AL, Khoury J, Iversen PO, Bergei C, Ose L, Tonstad S. Marked changes in plasma lipids and lipoproteins during pregnancy in women with familial hypercholesterolemia. Atherosclerosis. 2006 Feb 6. [Epub ahead of print].

  56. Aegerion Pharmaceuticals. FDA approves Aegerion Pharmaceuticals' Juxtapid (lomitapide) capsules for homozygous familial hypercholesterolemia (HoFH) [press release]. December 24, 2012. Available at http://ir.aegerion.com/releasedetail.cfm?ReleaseID=728650. Accessed: January 10, 2013.

  57. Buchwald H, Matts JP, Fitch LL, Campos CT, Sanmarco ME, Amplatz K, et al. Changes in sequential coronary arteriograms and subsequent coronary events. Surgical Control of the Hyperlipidemias (POSCH) Group. JAMA. 1992 Sep 16. 268(11):1429-33. [Medline].

  58. Nainggolan L. Lomitapide approved for homozygous familial hypercholesterolemia. Medscape Medical News. December 24, 2012. Available at http://www.medscape.com/viewarticle/776699. Accessed: January 10, 2013.

  59. Rader DJ, Cohen J, Hobbs HH. Monogenic hypercholesterolemia: new insights in pathogenesis and treatment. J Clin Invest. 2003. 111(12):1795-803. [Medline]. [Full Text].

  60. Zuliani G, Vigna GB, Corsini A, Maioli M, Romagnoni F, Fellin R. Severe hypercholesterolaemia: unusual inheritance in an Italian pedigree. Eur J Clin Invest. 1995 May. 25(5):322-31. [Medline].

 
Previous
Next
 
Metacarpophalangeal joint tendon xanthomas in a 45-year-old man with heterozygous familial hypercholesterolemia.
Table 1. LDLc Target levels and levels Indicating Therapeutic Lifestyle Changes (TLC) and Drug Therapy
 



Risk Category



 



LDLc Target level,



mg/dL



 



LDLc level Indicating TLC,



mg/dL



 



LDLc level for Considering Drug Therapy,



mg/dL*



High risk:



CHD or CHD risk equivalent



(10-y risk >20%)



<100



Optional goal <70



>100 >100
Moderately high risk:



More than 2 risk factors



(10-y risk 10-20%)



130



Optional goal <100



>130 >130



(100-129 may consider drug options)



Moderate risk:



More than 2 risk factors



(10-y risk 10%)



<130 >130 >160
Lower risk:



0-1 risk factor



<160 >160 >190



(160-189 LDL-lowering drug optional)



*The 2004 update recommended that when statin therapy is initiated in patients at high or moderately high risk, a dose and strength should be chosen that achieves at least a 30-40% LDLc reduction (see Table 3).
Table 2. Recommended Dietary Intake
 



Food Category



 



Typical US Diet



 



NCEP Diet



 



Diet for FH



Cholesterol, mg/d 500 < 200 100
Total fat, % energy (calories) 40 25-35 20
Saturated fat, % energy (calories) 14 < 7 < 6
Carbohydrate, % energy (calories) 45 50-60 65
Protein, % energy (calories) Approximately 15 15 N/A
Table 3. Statin and Statin Combination Approved Doses, Expected LDLc Decrease, and Dose Required for 30-40% LDLc Reduction
 



Statin



 



FDA-Approved Dose



 



Expected LDLc Decrease



 



Dose Required for 30-40% LDLc Reduction



Atorvastatin 10-80 mg daily 35-60% 10 mg
Fluvastatin 20-40 mg at bedtime 20-30% 40 mg qd/bid
40 mg bid 35% 40 mg bid
Extended-release fluvastatin



(Lescol XL)



80 mg at bedtime 35-38% 80 mg at bedtime
Lovastatin 20-80 mg at supper 25-48% 40 mg at dinner
Extended-release lovastatin



(Altoprev)



20-60 mg at bedtime 25-45% 60 mg at bedtime
Pravastatin 40-80 mg at bedtime 30-40% 40 mg at bedtime
Rosuvastatin 10-40 mg daily 40-60% 5 mg daily
Simvastatin 20-80 mg daily at bedtime 35-50% 20 mg at bedtime
Simvastatin + ezetimibe



(Vytorin)



10/20 mg



10/40 mg



10/80 mg



at bedtime



50-60% 10/20 mg at bedtime
Previous
Next
 
 
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.