What is Evolocumab (Repatha) used for?

What is Evolocumab (Repatha) Used For?

Evolocumab is a PCSK9 inhibitor used to dramatically lower LDL cholesterol (by approximately 59-64%) and reduce cardiovascular events in adults with established cardiovascular disease, as well as to treat primary hyperlipidemia and familial hypercholesterolemia in both adults and children ≥10 years old. 1

Primary Indications

Cardiovascular Risk Reduction (Secondary Prevention)

• Evolocumab reduces the risk of major adverse cardiovascular events—including CV death, myocardial infarction, stroke, unstable angina requiring hospitalization, or coronary revascularization—in adults with established cardiovascular disease. 1
• The FOURIER trial demonstrated a 15% reduction in the composite cardiovascular endpoint (11.3% vs. 9.8%; P < 0.001) and a 20% reduction in CV death, MI, or stroke (7.4% to 5.9%; P < 0.001) in 27,564 patients with prior atherosclerotic cardiovascular disease. 2, 3
• This cardiovascular benefit occurs when evolocumab is added to maximally tolerated statin therapy, achieving median LDL-C levels as low as 30 mg/dL. 2, 3

Primary Hyperlipidemia and Mixed Dyslipidemia

• Evolocumab is indicated as an adjunct to diet, alone or combined with other LDL-lowering therapies, in adults with primary hyperlipidemia or mixed dyslipidemia who require additional LDL-C reduction beyond maximally tolerated statin therapy. 4, 1
• When added to maximally tolerated statin therapy, evolocumab achieves an additional 58-64% LDL-C reduction. 4, 5

Heterozygous Familial Hypercholesterolemia (HeFH)

• Evolocumab is approved for adults and pediatric patients aged 10 years and older with HeFH requiring additional LDL-C lowering beyond diet and maximally tolerated statin therapy. 4, 1
• For patients 30-75 years with HeFH taking maximal tolerated statin and ezetimibe with LDL-C ≥100 mg/dL, adding evolocumab may be reasonable. 4

Homozygous Familial Hypercholesterolemia (HoFH)

• Evolocumab is indicated as an adjunct to other LDL-C-lowering therapies in adults and pediatric patients aged 10 years and older with HoFH to reduce LDL-C. 1
• In HoFH patients, evolocumab significantly lowered LDL-C levels by approximately 30% versus placebo when added to statins with or without ezetimibe. 5

Mechanism and Additional Effects

How Evolocumab Works

• Evolocumab is a fully human monoclonal antibody that binds to PCSK9 protein, preventing PCSK9 from degrading LDL receptors, thereby increasing the number of LDL receptors available to clear circulating LDL-C from the bloodstream. 6, 7
• Unlike statins that inhibit cholesterol synthesis, evolocumab enhances LDL receptor recycling for more efficient LDL-C clearance. 6

Beyond LDL-C Reduction

• Additional lipid effects include a 27% reduction in lipoprotein(a), 51% reduction in non-HDL-C, and 16% reduction in triglycerides. 2
• These plaque stabilization properties contribute to the cardiovascular benefits observed in clinical trials. 2

Dosing and Administration

Standard Dosing

• The recommended dose is 140 mg subcutaneously every 2 weeks OR 420 mg subcutaneously once monthly for ASCVD, primary hypercholesterolemia, or HeFH. 4, 1
• For HoFH, the recommended starting dose is 420 mg subcutaneously once monthly, with the option to increase to 420 mg every 2 weeks if more LDL-C reduction is needed after 12 weeks. 4, 1

Administration Details

• Evolocumab is administered subcutaneously and may take up to 15 seconds with the prefilled autoinjector or syringe, or about 5 minutes with the on-body infusor. 1

Safety Profile

Contraindications and Precautions

• The only contraindication is a history of hypersensitivity to evolocumab. 4, 1
• Patients sensitive to latex should be aware that some formulations contain dry natural rubber (a derivative of latex) in the needle cover, though latex-free options are available. 1

Tolerability

• Evolocumab is generally well-tolerated with no clinically significant drug-drug interactions identified. 4
• Common adverse events include injection-site reactions (2.1% vs. 1.6% with placebo), with most other adverse events occurring at similar frequencies to placebo. 3, 8
• Neurocognitive events were reported more frequently in some studies, though the risk did not vary significantly according to achieved LDL cholesterol levels. 8

Clinical Considerations

Patient Selection

• Evolocumab must be combined with maximally tolerated statin therapy to achieve the plaque stabilization and cardiovascular event reduction demonstrated in clinical trials. 2, 4
• The American College of Cardiology recommends evolocumab for adults with established clinical ASCVD on atorvastatin ≥20 mg or equivalent who need additional LDL-C reduction. 4
• Efficacy is maintained in the longer term, making it suitable for chronic management of hyperlipidemia and cardiovascular risk. 5, 8