Treatment of drug-resistant hypercholesterolemia
- Robert S Rosenson, MD
Robert S Rosenson, MD
- Section Editor — Lipids
- Professor of Medicine
- Mount Sinai School of Medicine
- Director, Cardiometabolic Disorders
- Mount Sinai Heart
- Sarah D de Ferranti, MD, MPH
Sarah D de Ferranti, MD, MPH
- Director, Preventive Cardiology Clinic
- Department of Cardiology
- Boston Children's Hospital
- Paul Durrington, MD
Paul Durrington, MD
- Professor of Medicine
- Physician to Manchester Royal Infirmary
- University of Manchester
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 "Treatment of lipids (including hypercholesterolemia) in secondary prevention", section on 'Summary and recommendations' and "Treatment of lipids (including hypercholesterolemia) in primary prevention", section on 'Summary and recommendations'.)
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 "Intensity of lipid lowering therapy 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", section on 'Familial hypercholesterolemia'.)
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- LDL-C GOALS
- REFERRAL TO A SPECIALIST
- PCSK9 ANTIBODIES
- LDL APHERESIS
- Efficacy and safety
- Clinical use
- Recommendations of others
- PARTIAL ILEAL BYPASS SURGERY
- LIVER TRANSPLANTATION
- PORTOCAVAL SHUNT
- POTENTIAL FUTURE APPROACHES
- Gene therapy
- CETP inhibition
- Antibody removal of resistin
- SOCIETY GUIDELINE LINKS
- SUMMARY AND RECOMMENDATIONS