What is the indication and usage of Repatha (evolocumab) for patients with high cholesterol?

Repatha (Evolocumab): Indications and Usage

Repatha is FDA-approved for four primary indications: reducing major adverse cardiovascular events in adults with established cardiovascular disease, lowering LDL-C in adults with primary hyperlipidemia including heterozygous familial hypercholesterolemia (as adjunct to diet with or without statins), reducing LDL-C in pediatric patients ≥10 years with HeFH, and lowering LDL-C in adults and pediatric patients ≥10 years with homozygous familial hypercholesterolemia. 1

FDA-Approved Indications

Cardiovascular Risk Reduction

• Repatha reduces the risk of major adverse cardiovascular events (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 (HR 0.85; 95% CI 0.79-0.92; P<0.001) when evolocumab was added to maximally tolerated statin therapy in 27,564 patients with prior MI, stroke, or PAD. 2, 3

Primary Hyperlipidemia and Heterozygous Familial Hypercholesterolemia (HeFH)

• Repatha is indicated as adjunct to diet, alone or in combination with other LDL-C-lowering therapies, in adults with primary hyperlipidemia including HeFH. 1
• Evolocumab reduces LDL-C by 64% (140 mg every 2 weeks) or 58% (420 mg monthly) when added to maximally tolerated statin therapy. 2, 3
• For pediatric patients aged 10 years and older with HeFH, Repatha is indicated as adjunct to diet and other LDL-C-lowering therapies. 1

Homozygous Familial Hypercholesterolemia (HoFH)

• Repatha is indicated as adjunct to other LDL-C-lowering therapies in adults and pediatric patients aged 10 years and older with HoFH. 1
• Initial dosing for HoFH is 420 mg subcutaneously once monthly, with escalation to 420 mg every 2 weeks if inadequate LDL-C reduction after 12 weeks. 3

Dosing Regimens

Standard Dosing

• For adults with ASCVD, primary hypercholesterolemia, or HeFH: 140 mg subcutaneously every 2 weeks OR 420 mg subcutaneously once monthly. 2, 3
• Both regimens provide comparable LDL-C reduction and can be selected based on patient preference. 2, 3
• For pediatric patients (≥10 years) with HeFH: same dosing as adults (140 mg every 2 weeks or 420 mg monthly). 3

HoFH-Specific Dosing

• Start with 420 mg subcutaneously once monthly. 3
• If LDL-C reduction is inadequate after 12 weeks, increase to 420 mg every 2 weeks. 3
• For patients on LDL apheresis, may initiate 420 mg every 2 weeks to correspond with apheresis schedule; administer after apheresis is complete. 2

Administration Details

• The 420 mg dose is administered using either the prefilled single-dose on-body infuser OR three consecutive 140 mg injections within 30 minutes at different injection sites. 2, 3
• Injection sites include thigh, abdomen, or upper arm; rotate sites with each injection. 3

Clinical Decision Algorithm for Use

When to Consider Repatha

Step 1: Identify High-Risk Patients

• Adults with established ASCVD (prior MI, stroke, PAD) who remain at high cardiovascular risk. 2
• Adults with primary hyperlipidemia or HeFH on maximally tolerated statin therapy with LDL-C ≥70 mg/dL. 2
• Pediatric patients ≥10 years with HeFH or HoFH requiring additional LDL-C lowering. 1

Step 2: Optimize Statin Therapy First

• Ensure patient is on maximally tolerated high-intensity statin therapy before adding Repatha. 2
• For very high-risk patients with ASCVD and LDL-C ≥70 mg/dL despite maximal statin therapy, addition of nonstatin therapy like Repatha should be considered. 2

Step 3: Consider Cost and Patient Preference

• Discuss net benefit, safety, and cost with patient before initiating combination therapy. 2
• Ezetimibe may be preferred by many patients due to lower cost, though it provides less LDL-C reduction (18-25%) compared to evolocumab (58-64%). 2, 4
• Both evolocumab and alirocumab (alternative PCSK9 inhibitor) have demonstrated cardiovascular outcomes benefit. 2, 4

Safety Profile and Contraindications

Contraindications

• History of hypersensitivity to evolocumab is an absolute contraindication. 2, 3

Common Adverse Effects

• Nasopharyngitis, upper respiratory tract infection, influenza, back pain, and injection site reactions are the most common adverse effects. 2, 3
• In patients with ASCVD specifically: diabetes, nasopharyngitis, and upper respiratory tract infection. 2

Important Safety Considerations

• No evidence of increased cognitive adverse effects was observed in the FOURIER or EBBINGHAUS trials. 2, 3
• If serious hypersensitivity reaction occurs, discontinue therapy immediately, treat according to standard of care, and monitor until symptoms resolve. 2
• Latex-sensitive patients should be advised that needle covers on the products contain latex. 2, 3

Key Clinical Pitfalls to Avoid

• Do not initiate Repatha without first maximizing statin therapy unless the patient has documented statin intolerance. 2
• Do not overlook cost considerations—while PCSK9 inhibitor costs have decreased, they remain substantially more expensive than ezetimibe, which also has cardiovascular outcomes data. 2
• For HoFH patients, do not forget to reassess at 12 weeks and increase dosing frequency if LDL-C reduction is inadequate. 3
• In patients on apheresis, coordinate Repatha administration to occur after apheresis is complete to avoid removing the medication. 2