What is the treatment regimen for a patient with high cholesterol and a history of cardiovascular events, such as heart attack, stroke, or peripheral artery disease, using Repatha (evolocumab)?

Repatha (Evolocumab) Treatment Regimen for High Cholesterol with Cardiovascular Disease History

For patients with established atherosclerotic cardiovascular disease (ASCVD) and elevated LDL-C despite statin therapy, administer Repatha 140 mg subcutaneously every 2 weeks OR 420 mg subcutaneously once monthly—both regimens provide equivalent LDL-C reduction of approximately 60%. 1, 2

Patient Eligibility Criteria

Before initiating Repatha, confirm the following:

• Established ASCVD must include history of myocardial infarction, acute coronary syndrome, stroke, transient ischemic attack, peripheral artery disease, or coronary/arterial revascularization 1
• Maximally tolerated statin therapy for at least 4 weeks at stable dose, preferably high-intensity 3
• LDL-C remains ≥70 mg/dL despite optimal statin therapy 1, 3
• For very high-risk patients (multiple major ASCVD events or one major event plus multiple high-risk conditions), target LDL-C <55 mg/dL with ≥50% reduction from baseline 3

Standard Dosing Regimens

Primary Dosing Options (Choose One):

• 140 mg subcutaneously every 2 weeks 1, 2, 4
• 420 mg subcutaneously once monthly 1, 2, 4

Both regimens achieve comparable efficacy (64% and 58% LDL-C reduction respectively when added to maximally tolerated statin) 2

Administration Details:

• Inject into thigh, abdomen, or upper arm 1, 2
• Rotate injection sites with each dose 2
• For 420 mg monthly dose: use prefilled single-dose on-body infusor OR give 3 consecutive 140 mg injections within 30 minutes at different sites 2, 4
• Administration takes approximately 15 seconds with autoinjector/syringe or 5 minutes with on-body infusor 4

Special Population: Homozygous Familial Hypercholesterolemia (HoFH)

• Initial dose: 420 mg subcutaneously once monthly 1, 2
• Dose escalation: If inadequate LDL-C reduction after 12 weeks, increase to 420 mg every 2 weeks 1, 2
• For patients on lipid apheresis, start with 420 mg every 2 weeks timed after apheresis treatment 4

Cardiovascular Outcomes Benefit

Repatha reduces major adverse cardiovascular events by 15-20% in patients with established ASCVD 3, 5:

• Composite endpoint reduction (CV death, MI, stroke, revascularization, or hospitalization for unstable angina): HR 0.85 (95% CI 0.79-0.92; P<0.001) 2
• Provides 59-64% additional LDL-C reduction when added to statin therapy 3
• Monotonic relationship between LDL-C reduction and clinical event reduction, even at very low LDL-C levels 5

Safety Profile and Monitoring

Common Adverse Effects:

• Nasopharyngitis, upper respiratory tract infection, influenza 1, 2
• Back pain and injection site reactions 2
• Myalgia (comparable to ezetimibe in statin-intolerant patients) 6

Key Safety Points:

• No laboratory monitoring required for hepatic or muscle toxicity (unlike statins) 6
• No increased cognitive adverse effects demonstrated in FOURIER or EBBINGHAUS trials 2, 6
• No excess adverse events in patients achieving very low LDL-C levels over 78 weeks 6
• Well-tolerated in long-term studies extending several years 6

Contraindications and Precautions

Absolute Contraindication:

• History of serious hypersensitivity reaction to evolocumab or any excipients 6, 4

Latex Sensitivity Warning:

• Some prefilled autoinjectors and syringes contain dry natural rubber (latex derivative) in needle cover 2, 4
• Single-dose on-body infusor is NOT made with natural rubber latex 4
• Check carton labeling to identify latex-free options for latex-sensitive patients 2, 4

Clinical Decision Algorithm

For patients with ASCVD judged to be very high-risk (Table 4 criteria: multiple major ASCVD events OR one major event plus multiple high-risk conditions such as age ≥65, diabetes, hypertension, CKD, current smoking, prior CABG/PCI, or persistently elevated LDL-C ≥100 mg/dL despite maximal therapy):

1. Maximize statin therapy first 1, 3
2. If LDL-C remains ≥70 mg/dL or non-HDL-C ≥100 mg/dL, add Repatha following clinician-patient discussion about net benefit, safety, and cost 1
3. Choose either 140 mg every 2 weeks or 420 mg monthly based on patient preference 1, 2

The 2019 AHA/ACC guidelines assign Class IIa recommendation (reasonable to add) for PCSK9 inhibitors in very high-risk ASCVD patients on maximally tolerated statin with LDL-C ≥70 mg/dL 1, while the 2022 ACC Expert Consensus confirms Class IIa, Level B evidence for cardiovascular event reduction 3.