Conventional Therapies for Treating FH

Statin drugs are first-line, with a goal of reducing LDL-C by 50%. In patients with the highest risk of CVD, the recommended LDL-C goal is < 100 mg/dL.1 (Table 3) Reduction in CVD risk is directly correlated with higher statin dose intensity, regardless of LDL-C levels.1 Moderate-intensity statins (eg, simvastatin and pitavastatin) may be utilized but are less likely to achieve adequate LDL-C lowering than are high-intensity agents (eg, atorvastatin and rosuvastatin), which should be used as aggressive initial treatment.2 Individuals who are unable to tolerate high-dose statins and require additional LDL-C lowering may benefit from nonstatin therapies.1

Ezetimibe, which inhibits cholesterol absorption in the small intestine, is another conventional cholesterol-lowering agent. Bile acid sequestrants and niacin are limited in their use, due to adverse effects (gastrointestinal events and flushing, respectively).1

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Contemporary Therapies

Mipomersen, a second-generation antisense oligonucleotide, works by pairing with the coding region of the apo-B-100 mRNA and is used as an adjunct to lipid-lowering agents and lifestyle modification in patients with HoFH.1 It has been found effective both in patients with HeFH and with HoFH and severe hypercholesterolemia. For example, one study conducted in patients with HeFH who were treated with mipomersen or placebo in addition to conventional lipid-lowering agents found significantly greater mean percentage reduction in LDL-C with mipomersen than with placebo.8 Mipomersen also resulted in significant reductions in apo B-100, total cholesterol, and non-HDL cholesterol.8 Similar results were obtained in studies of patients with HoFH.9 Common adverse events included injection site reactions and flu-like symptoms as well as elevations in alanine aminotransferase and increased liver fat.8,9

Lomitapide, a selective microsomal triglyceride protein (MTP) inhibitor, is indicated as an adjunct to lifestyle modifications and other lipid-lowering treatments in patients with HoFH.1 Inhibition of MTP prevents the synthesis of very low-density lipoproteins, thereby reducing circulating LDL-C levels.10 A single-arm trial of lomitapide plus concomitant lipid-lowering strategies in patients with HoFH found significant reductions of LDL-C by an average of 50% from baseline after the 26-week efficacy phase.11 Adverse effects include elevation in aminotransferase levels and hepatic steatosis. Additional adverse effects are gastrointestinal, and there are drug-drug interactions with several agents, including warfarin.1