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Treatment of drug-resistant hypercholesterolemia

Robert S Rosenson, MD
Sarah D de Ferranti, MD, MPH
Paul Durrington, MD
Section Editor
Mason W Freeman, MD
Deputy Editor
Gordon M Saperia, MD, FACC


Hypercholesterolemia, and in particular, an elevated level of serum (or plasma) low density lipoprotein cholesterol (LDL-C), is associated with an increased risk of adverse cardiovascular events. Lipid lowering drug therapy, particularly with statins, is indicated to decrease the risk of cardiovascular events in most individuals with established atherosclerotic cardiovascular disease and in many who are at high risk. (See "Management of elevated low density lipoprotein-cholesterol (LDL-C) in primary prevention of cardiovascular disease", section on 'Summary and recommendations' and "Management of low density lipoprotein cholesterol (LDL-C) in secondary prevention of cardiovascular disease".)

Statins are the preferred therapy for most patients requiring treatment of dyslipidemia and in particular those with an elevated LDL-C. The goals of therapy are discussed elsewhere. (See "Management of low density lipoprotein cholesterol (LDL-C) in secondary prevention of cardiovascular disease".)

If after treatment with the maximal tolerated dose of statin the patient has not achieved the LDL-C goal, a number of other agents are available with varying levels of evidence for clinical benefits. These agents include nicotinic acid (niacin), bile acid sequestrants, and ezetimibe and their use is discussed elsewhere. (See "Low density lipoprotein cholesterol lowering with drugs other than statins and PCSK9 inhibitors".)

However, some patients, including young individuals with severe hypercholesterolemia such as occurs in familial hypercholesterolemia, are unable to sufficiently lower their LDL-C to values with the use of these drugs. These individuals remain at high risk for cardiovascular events.

This topic will discuss therapeutic options for these individuals, including low density lipoprotein (LDL) apheresis, lomitapide, mipomersen, as well as a number of procedures that are rarely performed such as partial ileal bypass surgery, liver transplantation, and portocaval shunting. Gene therapy is a possible future alternative in selected patients such as those with familial hypercholesterolemia (FH), some of who have a defect in the LDL receptor. (See "Inherited disorders of LDL-cholesterol metabolism other than familial hypercholesterolemia", section on 'Familial combined hyperlipidemia'.)

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Literature review current through: Nov 2017. | This topic last updated: Jan 04, 2017.
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