Repatha (Evolocumab) Indications
Repatha is FDA-approved for lowering LDL-cholesterol in adults with primary hyperlipidemia (including heterozygous familial hypercholesterolemia) or mixed dyslipidemia as adjunct to diet and maximally tolerated statin therapy, for reducing cardiovascular events (MI, stroke, coronary revascularization) in adults with established atherosclerotic cardiovascular disease, and for treating both adults and pediatric patients (≥10 years) with homozygous familial hypercholesterolemia. 1
Primary Hyperlipidemia and Mixed Dyslipidemia
Adults with primary hyperlipidemia or mixed dyslipidemia who require additional LDL-C lowering beyond maximally tolerated statin therapy (with or without ezetimibe) are candidates for evolocumab. 1
The drug achieves an additional 58-64% LDL-C reduction when added to maximally tolerated statin therapy, with median LDL-C levels reaching as low as 30 mg/dL. 1, 2
Evolocumab also produces a 27% reduction in lipoprotein(a), 51% reduction in non-HDL-C, and 16% reduction in triglycerides. 2
Atherosclerotic Cardiovascular Disease (Secondary Prevention)
Adults with established clinical ASCVD (prior MI, stroke, or peripheral arterial disease) on atorvastatin ≥20 mg or equivalent who need additional LDL-C reduction qualify for evolocumab. 1
The FOURIER trial demonstrated that evolocumab reduced the composite endpoint of CV death, MI, stroke, revascularization, or hospitalization for unstable angina by 15% (11.3% vs. 9.8%; P < 0.001) in 27,564 patients with prior ASCVD. 2
The more stringent combined endpoint of CV death, MI, or stroke was reduced by 20% (7.4% to 5.9%; P < 0.001). 2
Heterozygous Familial Hypercholesterolemia (HeFH)
Adults and pediatric patients ≥10 years with HeFH requiring additional LDL-C lowering beyond diet and maximally tolerated statin therapy are indicated for evolocumab. 1
For patients 30-75 years of age with HeFH taking maximal tolerated statin and ezetimibe with LDL-C ≥100 mg/dL, adding evolocumab may be reasonable. 1
In severe primary hypercholesterolemia (baseline LDL-C ≥220 mg/dL) with LDL-C ≥130 mg/dL despite maximal tolerated statin and ezetimibe, evolocumab may be considered. 1
Homozygous Familial Hypercholesterolemia (HoFH)
Adults and pediatric patients ≥10 years with HoFH as adjunct to diet and other LDL-lowering therapies (statins, ezetimibe, LDL apheresis) are indicated for evolocumab. 1
In HoFH patients, evolocumab produces a mean LDL-C reduction of approximately 21-30% depending on dosing frequency, with sustained effects over median 4.1 years of treatment. 3
Of 61 patients receiving apheresis at enrollment in long-term studies, 16 were able to discontinue apheresis with evolocumab treatment. 3
Dosing by Indication
For ASCVD, primary hypercholesterolemia, or HeFH: Administer 140 mg subcutaneously every 2 weeks OR 420 mg subcutaneously once monthly in the abdomen, thigh, or upper arm. 1
For HoFH: Administer 420 mg subcutaneously once monthly; if more LDL-C reduction is needed after 12 weeks, may increase to 420 mg every 2 weeks. 1
For HoFH patients on LDL apheresis: May initiate 420 mg subcutaneously every 2 weeks to correspond with apheresis schedule; evolocumab should be given after apheresis is complete. 1
To administer the 420-mg dose, either use the prefilled single-dose on-body infuser or give 3 consecutive 140-mg injections within 30 minutes. 1
Key Prescribing Considerations
Prior authorization is typically required, with documentation of established ASCVD or familial hypercholesterolemia diagnosis, evidence of maximally tolerated statin therapy, and current LDL-C levels above target despite optimal therapy. 4
The only contraindication is history of hypersensitivity to evolocumab. 1
No clinically significant drug-drug interactions have been identified for evolocumab. 1
Common adverse effects include nasopharyngitis, upper respiratory tract infection, influenza, back pain, and injection site reactions; no evidence of increased cognitive adverse effects was observed in FOURIER or EBBINGHAUS trials. 1