Indications for Starting Repatha (Evolocumab)
Repatha (evolocumab) should be initiated in patients with familial hypercholesterolemia or established atherosclerotic cardiovascular disease who fail to achieve LDL-C goals despite maximally tolerated statin therapy plus ezetimibe.
Primary Indications for Repatha
Repatha is indicated for:
Patients with established ASCVD who cannot achieve LDL-C targets (<1.8 mmol/L or <70 mg/dL) despite maximally tolerated statin plus ezetimibe 1
Heterozygous familial hypercholesterolemia (HeFH) patients with:
Homozygous familial hypercholesterolemia (HoFH) patients as adjunct to other LDL-C-lowering therapies 1, 3
Very high-risk patients with LDL-C ≥70 mg/dL despite maximally tolerated statin plus ezetimibe 1, 2
Treatment Algorithm
Step 1: Maximize Statin Therapy
- Begin with high-intensity statin therapy (aim for ≥50% LDL-C reduction) 1, 2
- Ensure patient adherence before considering additional therapy
Step 2: Add Ezetimibe
- If LDL-C remains above target after maximally tolerated statin
- Ezetimibe typically provides an additional 15-25% LDL-C reduction 2
Step 3: Consider Repatha When:
- For ASCVD patients: LDL-C remains ≥70 mg/dL (1.8 mmol/L) despite steps 1-2 1
- For FH patients: LDL-C thresholds as noted above 1, 2
LDL-C Targets by Risk Category
| Risk Category | LDL-C Target |
|---|---|
| Very high risk ASCVD | <1.8 mmol/L (<70 mg/dL) or ≥50% reduction [1] |
| High risk | <2.5 mmol/L (<100 mg/dL) [1] |
| FH without ASCVD | <2.5 mmol/L (<100 mg/dL) [2] |
| FH with ASCVD | <1.8 mmol/L (<70 mg/dL) [2] |
Administration and Dosing
- Standard dosing: 140 mg subcutaneously every 2 weeks or 420 mg once monthly 1
- For HoFH: 420 mg subcutaneously once monthly; may increase to 420 mg every 2 weeks if inadequate response after 12 weeks 1, 3
- Administer in thigh, abdomen, or upper arm 1
Efficacy
- Reduces LDL-C by an additional 50-60% beyond statin therapy 4, 5
- Reduces apolipoprotein B by 31-61% 5
- Reduces lipoprotein(a) by 12-36% 5
- Maintains efficacy long-term (median 4.1 years in FH patients) 3
Safety Profile
- Generally well-tolerated with low incidence of adverse events 4, 6
- Most common side effects: nasopharyngitis, injection site reactions, influenza, arthralgia, and back pain 1, 5
- No significant increase in cognitive adverse effects observed in clinical trials 1
Special Considerations
- For HoFH patients: Some level of LDL receptor activity (>2%) is required for efficacy; not recommended in patients with negative/negative LDLR mutations 1
- For patients on apheresis: Consider initiating Repatha 420 mg every 2 weeks to coincide with apheresis schedule 1
- Monitor response: Check LDL-C 4-12 weeks after initiation; for monthly dosing, measure just before next scheduled dose 2
Common Pitfalls to Avoid
- Delayed intensification: Don't wait too long to add Repatha when LDL-C goals aren't met with statins and ezetimibe 2
- Inadequate goal setting: Focus on achieving ≥50% reduction from baseline in addition to specific LDL-C targets 2
- Poor adherence assessment: Always verify adherence to statin and ezetimibe before adding Repatha 1
- Ignoring additional risk factors: Lower LDL-C thresholds apply when additional risk factors are present 1
Repatha represents a powerful addition to lipid-lowering therapy for patients unable to achieve target LDL-C levels with conventional therapy, offering substantial reductions in cardiovascular risk through potent LDL-C lowering.