Ezetimibe for Statin-Intolerant Patients

Definition and Treatment Approach

The American College of Cardiology recommends ezetimibe as an appropriate treatment option for patients with statin intolerance, either as monotherapy or in combination with other non-statin therapies 1, 2, 3
Before initiating ezetimibe, confirm true statin intolerance by documenting that the patient has attempted at least 2 different statins, including at least one at the lowest approved daily dose, with adverse effects that resolved or improved upon dose reduction or discontinuation 2

Ezetimibe should be considered as the initial non-statin therapy for statin-intolerant patients, with a dosing of 10 mg orally once daily, achieving 15-20% reduction in LDL-C as monotherapy 1, 4
The American College of Cardiology recommends a target LDL-C of <55 mg/dL with ≥50% reduction from baseline for very high-risk patients 3

For very high-risk patients, start with ezetimibe 10 mg daily and reassess LDL-C at 4-6 weeks, adding bempedoic acid 180 mg daily if LDL-C remains ≥55 mg/dL despite ezetimibe 1, 2, 3, 4
For high-risk patients, start with ezetimibe 10 mg daily and add bempedoic acid 180 mg daily if LDL-C remains ≥70 mg/dL, considering PCSK9 inhibitors only if LDL-C remains significantly elevated 1, 2, 4

Reassess lipid profile 4-8 weeks after initiating ezetimibe and monitor liver enzymes (ALT/AST) at baseline and as clinically indicated 1, 5
Discontinue ezetimibe if persistent transaminase elevations ≥3× ULN occur 1

Bempedoic acid monotherapy (180 mg daily) or PCSK9 inhibitors as monotherapy may be considered if ezetimibe fails or is not tolerated 1, 2, 3, 4
Bile acid sequestrants may be considered if triglycerides <300 mg/dL, but are limited by gastrointestinal side effects 1, 4, 5