Which medications in the drug class HMG-CoA reductase inhibitors (statins) are used in the treatment of Familial Hypercholesterolemia?

Updated: Oct 04, 2021
  • Author: Mose July, MD, CCD; Chief Editor: Romesh Khardori, MD, PhD, FACP  more...
  • Print
Answer

HMG-CoA reductase inhibitors (statins)

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) [59] 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 (heterozygous FH 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 LDLc similar to atorvastatin 10 mg/d and simvastatin 20 mg/d. It is also indicated for the reduction of elevated total cholesterol, LDLc, and apoB, in children aged 8 years or older with heterozygous FH.

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.


Did this answer your question?
Additional feedback? (Optional)
Thank you for your feedback!