What is the role of Rapatha (evolocumab) in managing high cholesterol?

Role of Repatha (Evolocumab) in Managing High Cholesterol

Repatha (evolocumab) is a highly effective PCSK9 inhibitor that should be used in patients with established cardiovascular disease, familial hypercholesterolemia, or those with high cardiovascular risk who cannot reach LDL-C goals despite maximally tolerated statin therapy plus ezetimibe. 1, 2

Indications for Repatha

Repatha is FDA-approved for:

• Reducing risk of major adverse cardiovascular events (CV death, MI, stroke, unstable angina, coronary revascularization) in adults with established cardiovascular disease 2
• As adjunct to diet, alone or with other LDL-C-lowering therapies in adults with primary hyperlipidemia, including heterozygous familial hypercholesterolemia (HeFH) 2
• As adjunct to diet and other LDL-C-lowering therapies in pediatric patients ≥10 years with HeFH 2
• As adjunct to other LDL-C-lowering therapies in adults and pediatric patients ≥10 years with homozygous familial hypercholesterolemia (HoFH) 2

Patient Selection Priorities

Priority should be given to:

1. Patients with established ASCVD and LDL-C ≥70 mg/dL despite maximally tolerated statin plus ezetimibe 1
2. Patients with familial hypercholesterolemia (heterozygous or homozygous) 1
3. Statin-intolerant patients with high cardiovascular risk 1, 3

Efficacy

Repatha demonstrates remarkable efficacy:

• Reduces LDL-C by 50-65% when added to statins 1, 4
• Reduces LDL-C by 59-75% compared to placebo in clinical trials 1
• In the landmark FOURIER trial, demonstrated 15% relative risk reduction in composite cardiovascular endpoints (HR 0.85,95% CI 0.79-0.92) 1, 5
• Showed 20% reduction in the combined endpoint of cardiovascular death, MI, or stroke (HR 0.80,95% CI 0.73-0.88) 1, 5
• Effectively lowers LDL-C in statin-intolerant patients (53-56% reduction vs. 37-39% with ezetimibe) 3

Dosing and Administration

• Adults with ASCVD or primary hypercholesterolemia: 140 mg subcutaneously every 2 weeks OR 420 mg subcutaneously once monthly 1
• Pediatric patients (≥10 years) with HeFH: Same as adult dosing 1
• Adults or pediatric patients (≥10 years) with HoFH: Initial dose of 420 mg subcutaneously once monthly, with option to increase to 420 mg every 2 weeks if additional LDL-C reduction needed after 12 weeks 1
• Patients on LDL apheresis: 420 mg subcutaneously every 2 weeks (after apheresis is complete) 1

Administration Pearls

• Administer subcutaneously into abdomen, thigh, or upper arm
• Rotate injection sites
• Can use prefilled single-dose on-body infuser or give 3 consecutive 140-mg injections within 30 minutes 1
• No specific laboratory monitoring required beyond routine lipid profile assessment 1

Safety Profile

Repatha has demonstrated a favorable safety profile:

• Common side effects: injection site reactions, nasopharyngitis, upper respiratory tract infection 1
• No significant differences in serious adverse events compared to placebo 1
• Can be safely used in patients with history of tendinitis (no known association with tendon disorders) 1
• Caution in patients with latex sensitivity (some needle covers contain dry natural rubber) 1

Clinical Pearls and Pitfalls

• Despite excellent efficacy and tolerability, high cost and prior authorization processes may restrict use 1
• The FOURIER trial showed benefit even in patients with very low LDL-C levels, suggesting "lower is better" for LDL-C 6, 5
• Unlike statins, Repatha does not require liver function tests, renal function, or complete blood counts monitoring 1
• Muscle-related adverse events appear less common with evolocumab (12%) than with ezetimibe (23%) in statin-intolerant patients 3