10
Treatment
Î For patients at low or moderate risk, lifestyle therapies should be
given an adequate trial (≥3 months) before initiation of drug therapy.
• Figure 1 shows a model for the steps in application of lifestyle therapies.
Î In patients at very high risk, drug therapy may be started concurrently
with lifestyle therapies.
• Figure 2 shows a model for progression of cholesterol-lowering drug therapy.
Î Although LDL-C has traditionally been the primary target of therapy,
non-HDL-C is a better primary target for modification than LDL-C.
• Non-HDL-C includes the cholesterol carried by all potentially atherogenic
particles including LDL, intermediate-density lipoproteins, very-low-density
lipoproteins (VLDL) and VLDL remnants, chylomicron remnants, and
lipoprotein (a).
• Apo B is considered an optional, secondary target for treatment.
Î When triglyceride levels are between 200 and 499 mg/dL, the targets
of therapy are non-HDL-C and LDL-C. When the triglyceride level is
very high (≥500 mg/dL, and especially if ≥1000 mg/dL), reducing the
level to <500 mg/dL to prevent pancreatitis becomes the primary goal
of therapy.
Î If the fasting triglyceride level is ≥1000 mg/dL, an agent that primarily
lowers triglycerides and VLDL-C (fibric acids, high-dose [2-4 g/d]
long-chain omega-3 fatty acids, or nicotinic acid) should be the first-
line agent.
Î For patients with triglyceride levels 500-999 mg/dL, a triglyceride-
lowering agent or a statin (if no history of pancreatitis) may be
reasonable first-line drug options.
Î HDL-C is not recommended as a target of therapy per se.
Î The presence of the metabolic syndrome indicates high potential to
benefit from lifestyle therapies (particularly weight loss if overweight/
obese) and increased physical activity.
Î Patients with severe hypercholesterolemia (LDL-C ≥190 mg/dL)
may not achieve goal levels of atherogenic cholesterol, even with
combination drug therapy.
• An alternative goal is to lower atherogenic cholesterol levels by at least 50%.
• Mipomersen, an injectable antisense inhibitor of apo B synthesis, when given in
combination with maximum tolerated doses of lipid-lowering therapy, can reduce
LDL-C by an additional 25% in homozygous FH patients.
a
• Lomitapide, an oral inhibitor of microsomal triglyceride transfer protein, can also
reduce LDL-C levels by up to 50% in homozygous FH patients on maximum
tolerated lipid-lowering therapy and LDL apheresis.
a
• For selected patients with severe hypercholesterolemia, LDL apheresis may be
considered. (See Table 14)
a
Mipomersen and lomitapide are available only through Risk Evaluation and Mitigation Strateg y
programs.
