When is Repatha (alirocumab) indicated?

When is Repatha (Evolocumab) Indicated?

Repatha is indicated to reduce cardiovascular events in adults with established atherosclerotic cardiovascular disease (ASCVD), and to lower LDL-cholesterol in patients with primary hyperlipidemia (including heterozygous familial hypercholesterolemia) or homozygous familial hypercholesterolemia when used as an adjunct to maximally tolerated statin therapy. 1

FDA-Approved Indications

Repatha has four distinct FDA-approved indications 1:

1. Cardiovascular Risk Reduction

• Adults with established cardiovascular disease to reduce the risk of:
  • CV death
  • Myocardial infarction
  • Stroke
  • Unstable angina requiring hospitalization
  • Coronary revascularization

This indication is supported by the FOURIER trial, which demonstrated that evolocumab reduced the primary composite endpoint (CV death, MI, stroke, revascularization, or hospitalization for unstable angina) in 27,564 patients with prior MI, stroke, or peripheral artery disease on atorvastatin ≥20 mg or equivalent 2.

2. Primary Hyperlipidemia (Including Heterozygous Familial Hypercholesterolemia)

• Adults with primary hyperlipidemia, including HeFH
• Pediatric patients aged ≥10 years with HeFH
• Used as adjunct to diet, alone or with other LDL-lowering therapies
• Provides additional 58-64% LDL-C reduction when added to maximally tolerated statin therapy 2

3. Homozygous Familial Hypercholesterolemia (HoFH)

• Adults and pediatric patients aged ≥10 years with HoFH
• Used as adjunct to other LDL-lowering therapies (statins, ezetimibe, LDL apheresis)
• Initial dose: 420 mg monthly; can increase to 420 mg every 2 weeks if inadequate response after 12 weeks 2, 1

Clinical Decision Algorithm

When to prescribe Repatha:

Step 1: Identify High-Risk Patients

Start with patients who have:

• Established ASCVD (prior MI, stroke, PAD, ACS, coronary artery disease), OR
• Heterozygous FH with or without ASCVD, OR
• Homozygous FH (any age ≥10 years)

Step 2: Assess Current LDL-C Lowering Therapy

Patient must be on:

• Maximally tolerated statin therapy (highest dose patient can tolerate without adverse effects)
• Consider adding ezetimibe first if not already prescribed 3

Step 3: Check LDL-C Levels on Current Therapy

According to 2022 ACC guidelines 2:

• ASCVD patients: Consider if LDL-C remains elevated despite maximal therapy
• Very high-risk patients: Target LDL-C <70 mg/dL (1.8 mmol/L); if not achieved, add PCSK9 inhibitor
• HeFH patients: If LDL-C ≥100 mg/dL (2.6 mmol/L) on statin + ezetimibe, PCSK9 inhibitor is reasonable 3
• HoFH patients: Typically require PCSK9 inhibitor regardless of LDL-C level due to severe genetic defect

Step 4: Confirm No Contraindications

• Only contraindication: History of serious hypersensitivity reaction to evolocumab 2, 1
• Latex sensitivity: Prescribe latex-free formulation if patient is latex-sensitive 1

Dosing Regimens

Standard dosing 1:

• 140 mg subcutaneously every 2 weeks, OR
• 420 mg subcutaneously once monthly

HoFH-specific dosing:

• Start with 420 mg monthly
• Increase to 420 mg every 2 weeks if clinically meaningful response not achieved in 12 weeks
• For patients on LDL apheresis: initiate 420 mg every 2 weeks to correspond with apheresis schedule; administer after apheresis session 2, 1

Key Clinical Considerations

Cardiovascular outcomes evidence:

• The FOURIER trial demonstrated clear mortality and morbidity benefits in patients with established ASCVD 2
• No increase in cognitive adverse effects observed in FOURIER or EBBINGHAUS trials 2
• Absolute benefit is greater in patients with baseline LDL-C ≥100 mg/dL 4

Common pitfalls to avoid:

• Don't wait too long: Initiate PCSK9 inhibitor therapy once it's clear that statin + ezetimibe combination is insufficient, rather than delaying for multiple medication adjustments
• Don't forget pediatric indications: Repatha is approved for children ≥10 years with HeFH or HoFH 1
• Don't overlook apheresis patients: These patients often benefit from PCSK9 inhibitors and may reduce or eliminate need for apheresis 5
• Prior authorization burden: Be prepared for insurance requirements; most require documentation of maximally tolerated statin therapy and inadequate LDL-C control 2

Practical administration:

• Assess LDL-C as early as 4 weeks after initiation to evaluate response 1
• Rotate injection sites (abdomen, thigh, upper arm) 1
• Can be self-administered at home using prefilled autoinjector or syringe 2
• Cost considerations: approximately $14,300/year; ensure patient has access and coverage 6