Can Repatha (evolocumab) and statin be taken together?

Can Repatha and Statin Be Taken Together?

Yes, Repatha (evolocumab) is specifically designed to be taken in combination with statin therapy and should not be used as monotherapy in most patients with cardiovascular disease. 1, 2

Guideline-Recommended Combination Approach

The combination of Repatha with statins is the standard evidence-based approach for high-risk patients who cannot achieve LDL-C targets with statins alone:

• Repatha must be added to maximally tolerated statin therapy as the foundation of treatment, not used as a replacement 3, 4
• The European Society of Cardiology and American College of Cardiology both recommend this combination strategy for patients with clinical atherosclerotic cardiovascular disease (ASCVD) who have LDL-C ≥70 mg/dL despite maximally tolerated statin therapy 1
• In the landmark FOURIER trial, two-thirds of patients were on high-intensity statins (atorvastatin ≥40 mg or rosuvastatin ≥20 mg) when evolocumab was added, demonstrating the combination's safety and efficacy 4

Stepwise Treatment Algorithm

The recommended sequence for lipid management follows this hierarchy:

1. Start with maximally tolerated high-intensity statin (atorvastatin 40-80 mg or rosuvastatin 20-40 mg daily) 4
2. Add ezetimibe 10 mg daily if LDL-C remains ≥70 mg/dL, providing an additional 15-25% LDL-C reduction 1, 5
3. Add Repatha only after statin plus ezetimibe trial if LDL-C still ≥70 mg/dL in very high-risk patients 3, 4

Clinical Evidence Supporting Combination Therapy

When Repatha is added to statin therapy, it provides an additional 50-60% reduction in LDL-C beyond what the statin achieves alone 1, 2:

• In the LAPLACE-2 trial, patients on background statin therapy who added Repatha 140 mg every 2 weeks achieved a 63% mean reduction in LDL-C compared to baseline 2
• The FOURIER trial demonstrated a 15% relative risk reduction in major cardiovascular events when evolocumab was added to maximally tolerated statin therapy 1, 4
• Patients with diabetes showed even greater absolute risk reduction with this combination approach 3

Safety Profile of the Combination

The combination of Repatha with statins has an excellent safety profile:

• No increased risk of cognitive deficits was observed in the EBBINGHAUS trial when evolocumab was added to statin therapy 1
• Adverse event rates are similar between combination therapy and statin monotherapy 5
• Patients achieving very low LDL-C levels (<30 mg/dL) on combination therapy showed similar safety profiles to those with higher LDL-C levels 1

Insurance Coverage Requirements

Understanding insurance criteria is critical for successful prior authorization:

• Documentation of maximally tolerated statin dose is mandatory—insurers require evidence that higher statin doses were attempted and either caused side effects or that the current dose is the maximum FDA-approved 4
• Proof of ezetimibe trial is required—patients must have tried ezetimibe for 6-12 weeks with inadequate response before Repatha approval 4
• Recent lipid panel showing LDL-C ≥70 mg/dL on current statin therapy must be submitted 4

Common Pitfalls to Avoid

Do not use Repatha as monotherapy in patients with ASCVD—the evidence base and FDA approval are specifically for combination with statin therapy 3, 2:

• The only exception is statin-intolerant patients who cannot tolerate any statin regimen, in which case Repatha can be combined with ezetimibe alone 4
• Do not skip the ezetimibe trial before adding Repatha, as insurers will deny coverage and ezetimibe provides substantial additional LDL-C lowering at much lower cost 3, 4
• Ensure proper documentation of "maximally tolerated" statin dose—this means either the maximum FDA-approved dose or the highest dose the patient can tolerate without unacceptable side effects 4

Specific Dosing When Combined with Statins

Repatha dosing options when added to statin therapy 2:

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

Both dosing regimens provide similar LDL-C reductions of approximately 60% when added to background statin therapy 2.