What are the alternatives to Repatha (evolocumab) for lowering low-density lipoprotein (LDL) cholesterol?

Alternatives to Repatha (Evolocumab) for LDL Cholesterol Lowering

Alirocumab (Praluent) is the most direct alternative to Repatha (evolocumab) with similar efficacy, safety profile, and mechanism of action for lowering LDL cholesterol. 1, 2

PCSK9 Inhibitor Alternative

Alirocumab (Praluent)

• Mechanism of action: Human monoclonal antibody to PCSK9 that binds to PCSK9 and increases the number of LDL receptors available to clear circulating LDL-C 1
• Efficacy: Reduces LDL-C by 45-58% when added to maximally tolerated statin therapy 1
• FDA-approved indications:
  • Reduces risk of MI, stroke, and unstable angina requiring hospitalization in adults with ASCVD 3
  • Lowers LDL-C in adults with primary hyperlipidemia (including heterozygous familial hypercholesterolemia) as adjunct to diet, alone or with other lipid-lowering therapies 3
  • Lowers LDL-C in adults with homozygous familial hypercholesterolemia (HoFH) 3
• Dosing:
  • Initial dose: 75 mg subcutaneously every 2 weeks or 300 mg every 4 weeks 3
  • Can be increased to 150 mg every 2 weeks if additional LDL-C reduction is needed 3
• Safety profile: Generally well-tolerated with adverse effects including nasopharyngitis, injection site reactions, influenza, noncardiac chest pain, and myalgia 1

Non-PCSK9 Inhibitor Alternatives

Ezetimibe

• Mechanism of action: Inhibits NPC1L1 protein in the small intestine, reducing cholesterol absorption 1
• Efficacy: Monotherapy reduces LDL-C by approximately 18%; when combined with statin therapy, provides an additional 25% reduction 1
• FDA-approved indications: Adjunct to diet to reduce total cholesterol, LDL-C, ApoB, and non-HDL-C in patients with primary hyperlipidemia 1
• Dosing: 10 mg orally once daily, with or without food 1
• Advantages:
  • Generally well-tolerated 1
  • Available as a generic medication (cost-effective) 1
  • Proven cardiovascular outcomes benefit in the IMPROVE-IT trial 1
• Safety profile: Common side effects include upper respiratory tract infection, diarrhea, arthralgia, sinusitis, and pain in extremities 1

Bile Acid Sequestrants

• Mechanism of action: Bind bile acids in the intestine, promoting hepatic conversion of cholesterol to bile acids 1
• Efficacy: Can reduce LDL-C by 15-30% 1
• Options include colesevelam, cholestyramine, and colestipol 1
• Considerations: May cause gastrointestinal side effects and can interact with other medications 1

Bempedoic Acid

• Newer non-statin medication that inhibits ATP citrate lyase, reducing cholesterol synthesis 1
• Can be used in statin-intolerant patients or as add-on therapy 1

Clinical Decision Algorithm

1. First-line alternative to Repatha: Alirocumab (Praluent)

   • Similar efficacy (45-58% LDL-C reduction) 1
   • Similar administration (subcutaneous injection) 3
   • Similar safety profile 2

2. If PCSK9 inhibitors are not suitable:

   • Ezetimibe (oral medication, 18-25% LDL-C reduction) 1
   • Consider adding bile acid sequestrants for additional LDL-C lowering 1

3. For statin-intolerant patients:

   • Alirocumab or ezetimibe as monotherapy 4, 5
   • Consider combination of non-statin therapies for greater efficacy 1

Important Considerations

• Cost implications: PCSK9 inhibitors (both Repatha and Praluent) are expensive (~$14,300/year) compared to generic ezetimibe 4, 5
• Insurance coverage: Insurance approval for PCSK9 inhibitors typically requires:
  • Documented HeFH and/or clinical ASCVD 5
  • LDL-C >100 mg/dL despite maximally tolerated lipid-lowering therapy 5
• Cardiovascular outcomes: Both alirocumab (ODYSSEY Outcomes trial) and ezetimibe (IMPROVE-IT trial) have demonstrated reduction in cardiovascular events 1
• Common pitfall: Failing to optimize statin therapy before adding non-statin agents. Ensure patients are on maximally tolerated statin therapy before considering alternatives or add-on therapies 1