Repatha (Evolocumab) and Statin Therapy Indication
Repatha is indicated for patients with established atherosclerotic cardiovascular disease (ASCVD) who have LDL-C ≥70 mg/dL despite maximally tolerated high-intensity statin therapy plus ezetimibe, targeting an LDL-C goal of <55 mg/dL. 1, 2
Primary Indication: Secondary Prevention in ASCVD
The foundation of therapy must be maximally tolerated high-intensity statin therapy (atorvastatin ≥40 mg or rosuvastatin ≥20 mg daily) before considering Repatha. 3 This stepwise approach is critical—statins remain first-line therapy for all patients at high cardiovascular risk. 1, 4
Specific Patient Populations Eligible for Repatha:
Very High-Risk ASCVD Patients:
- Patients with multiple major ASCVD events (recent acute coronary syndrome, history of MI, ischemic stroke, or symptomatic peripheral arterial disease) despite maximally tolerated statin plus ezetimibe 2
- Patients with one major ASCVD event plus multiple high-risk conditions: age ≥65 years, heterozygous familial hypercholesterolemia, history of coronary revascularization, diabetes, hypertension, CKD, current smoking, or persistently elevated LDL-C ≥100 mg/dL 2
- LDL-C must remain ≥70 mg/dL on maximally tolerated statin plus ezetimibe to qualify 1, 2
Familial Hypercholesterolemia:
- Heterozygous FH patients aged 30-75 years with LDL-C ≥100 mg/dL despite maximally tolerated statin plus ezetimibe 1, 2
- HeFH patients with additional risk factors (diabetes with target organ damage, lipoprotein(a) >50 mg/dL) and LDL-C ≥140 mg/dL 2
- Homozygous FH patients with residual LDL receptor activity >2% 2
Critical Stepwise Algorithm
Step 1: Initiate high-intensity statin therapy targeting ≥50% LDL-C reduction from baseline 1, 2
Step 2: Add ezetimibe if LDL-C remains ≥70 mg/dL after maximally tolerated statin therapy 1, 2 Ezetimibe must always be tried before Repatha due to lower cost and established safety profile. 5, 2
Step 3: Add Repatha only if LDL-C remains ≥70 mg/dL despite maximally tolerated statin plus ezetimibe 1, 2 Target LDL-C <55 mg/dL for very high-risk patients. 1, 2
Step 4: Assess LDL-C response 4 weeks after initiating Repatha therapy 2
Expected Clinical Benefit
Repatha provides an additional 50-60% reduction in LDL-C beyond statin therapy alone, with mean LDL-C levels of approximately 35 mg/dL achievable. 2, 6 The FOURIER trial demonstrated a 15% relative risk reduction in major cardiovascular events when evolocumab was added to maximally tolerated statin therapy. 2, 6
Special Considerations for Diabetes Patients
Diabetes patients with ASCVD derive particular benefit from Repatha therapy, showing greater absolute risk reduction compared to non-diabetic patients. 2 This is especially true for those with target organ damage or additional major risk factors. 2
Statin Intolerance Exception
For patients who cannot tolerate any statin regimen despite trying at least three different statins, Repatha can be added to ezetimibe alone if they have clinical ASCVD and LDL-C ≥70 mg/dL. 1, 2 Documentation of genuine statin intolerance is essential for insurance approval. 3
Common Pitfalls to Avoid
Do not prescribe Repatha for primary prevention (patients without established ASCVD or familial hypercholesterolemia)—no primary prevention trials exist, and the number needed to treat would be prohibitively high. 5 Patients with diabetes, hypertension, or multiple risk factors without established ASCVD do not qualify for Repatha. 5
Do not skip ezetimibe. Insurance will deny coverage if ezetimibe has not been tried first and documented as inadequate for 6-12 weeks. 3 This is a universal requirement across payers.
Ensure documentation of "maximally tolerated" statin dose—insurers require evidence that higher doses were attempted and caused side effects, or that the current dose is the maximum FDA-approved. 3
Safety Profile
Repatha shows no evidence of increased muscle symptoms, new-onset diabetes, hemorrhagic stroke, or neurocognitive effects, even at very low LDL-C levels (<20 mg/dL). 5, 2 Injection site reactions occur in <5% of patients. 5