Which medications are used in the treatment of familial hypercholesterolemia (FH)?

Updated: Oct 04, 2021
  • Author: Mose July, MD, CCD; Chief Editor: Romesh Khardori, MD, PhD, FACP  more...
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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, 54, 55, 56, 57]

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. ACL inhibitors [43, 44]  and PCSK9 inhibitors [33, 34, 46, 47] 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.

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)




FDA-Approved Dose


Expected LDLc Decrease


Dose Required for 30-40% LDLc Reduction


10-80 mg daily


10 mg


20-40 mg at bedtime


40 mg qd/bid

40 mg bid


40 mg bid

Extended-release fluvastatin

(Lescol XL)

80 mg at bedtime


80 mg at bedtime


20-80 mg at supper


40 mg at dinner

Extended-release lovastatin


20-60 mg at bedtime


60 mg at bedtime


40-80 mg at bedtime


40 mg at bedtime


10-40 mg daily


5 mg daily


20-80 mg daily at bedtime


20 mg at bedtime

Simvastatin + ezetimibe


10/20 mg

10/40 mg

10/80 mg

at bedtime


10/20 mg at bedtime

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