Ezetimibe Therapy for Lowering LDL Cholesterol

Primary Indications and Treatment Algorithm

The American College of Cardiology recommends ezetimibe as a second-line therapy after maximally tolerated statin therapy when LDL-C targets are not achieved, particularly in high-risk and very high-risk patients with atherosclerotic cardiovascular disease (ASCVD) 1, 2
For patients with clinical ASCVD who are receiving maximally tolerated statin therapy and whose LDL-C level remains ≥70 mg/dL, adding ezetimibe is reasonable, as recommended by the American College of Cardiology 2, 3
In patients 20-75 years with LDL-C ≥190 mg/dL who achieve <50% reduction in LDL-C while receiving maximally tolerated statin therapy and/or have LDL-C ≥100 mg/dL, ezetimibe therapy is reasonable, according to the American College of Cardiology 2, 4
For patients with diabetes who have <50% reduction in LDL-C on maximally tolerated statin therapy (and LDL-C ≥100 mg/dL or non-HDL-C ≥130 mg/dL), ezetimibe may be considered as the initial non-statin agent, as suggested by the American College of Cardiology 5, 6

Patients with clinical ASCVD who are on maximally tolerated statin therapy and have LDL-C ≥70 mg/dL should be considered for ezetimibe therapy, as recommended by the American College of Cardiology 2, 3
Add ezetimibe as second-line therapy before considering PCSK9 inhibitors in very high-risk patients, according to the BMJ guideline 1, 7
Patients with severe hypercholesterolemia (LDL-C ≥190 mg/dL) should be considered for ezetimibe therapy, as recommended by the American College of Cardiology 2, 4
Patients with diabetes and 10-year ASCVD risk ≥7.5% or high-risk features should be considered for ezetimibe therapy, according to the American College of Cardiology 5, 8

Ezetimibe is preferred as the initial non-statin therapy due to demonstrated safety, tolerability, convenience, and single-tablet daily dosing, as recommended by the American College of Cardiology 5, 6
Bile acid sequestrants may be considered as an alternative if patients have an inadequate response to ezetimibe or are ezetimibe-intolerant, but only if fasting triglycerides are <300 mg/dL, as suggested by the American College of Cardiology 5, 6
Referral to a lipid specialist is recommended for patients with statin intolerance, baseline LDL-C ≥190 mg/dL not due to secondary causes, complex mixed dyslipidemias, or severe hypertriglyceridemia, according to the American College of Cardiology 6, 8