What are the alternatives to Repatha (evolocumab) for managing muscle aches as a side effect?

Alternatives to Repatha for Managing Muscle Aches

For patients experiencing muscle aches on Repatha (evolocumab), switching to inclisiran (Leqvio) is the recommended alternative as it has a different mechanism of action and administration schedule that may reduce muscle-related side effects.

Understanding Muscle Aches with PCSK9 Inhibitors

Muscle-related symptoms are reported with PCSK9 inhibitors like Repatha, though clinical trials suggest these are less common than with statins. When evaluating muscle aches:

• Determine if symptoms are truly medication-related (only about 1% of muscle pain is actually causally related to lipid-lowering medications) 1
• Assess timing of symptoms in relation to medication administration
• Rule out other causes of myalgia (polymyalgia rheumatica, inflammatory myositis, etc.)

Alternative Medication Options

First-Line Alternative: Inclisiran (Leqvio)

• Mechanism: Small interfering RNA that inhibits PCSK9 synthesis (different from antibody-based inhibition)
• Administration: Only requires dosing every 6 months after initial doses
• Benefit: Less frequent injections may reduce injection site reactions and perceived muscle symptoms

Second-Line Alternatives:

1. Bempedoic acid 1

   • ACL inhibitor that works upstream in cholesterol synthesis
   • Oral administration (180 mg daily)
   • 17-18% additional LDL-C reduction when added to statins
   • May cause hyperuricemia and tendon disorders
   • Less muscle effects than statins as it requires activation in the liver, not muscle tissue

2. Alirocumab (Praluent) 1

   • Alternative PCSK9 inhibitor with similar efficacy (45-58% LDL-C reduction)
   • Different antibody structure may be tolerated differently
   • Some patients who react to one monoclonal antibody may tolerate another

3. Ezetimibe 1

   • Lower potency (additional 15-20% LDL-C reduction)
   • Well-tolerated oral medication
   • Can be used in combination with other agents

Management Approach for Muscle Symptoms

1. Temporary discontinuation trial

   • Pause Repatha for 2-4 weeks to determine if symptoms resolve
   • If symptoms persist, muscle aches likely have another cause

2. Re-challenge strategy

   • If symptoms resolved during discontinuation, consider re-challenge to confirm causality
   • If symptoms recur, switch to alternative therapy

3. Non-pharmacological approaches

   • Physical activity and aerobic exercise may help reduce pain severity 1
   • Consider evaluation for vitamin D deficiency which can contribute to muscle symptoms

Special Considerations

• Documentation: Thoroughly document the nature of muscle symptoms, as true statin-related myalgia is much less common than perceived statin-related symptoms 1
• Combination therapy: Consider combination of lower doses of multiple agents to achieve LDL-C goals while minimizing side effects
• Monitoring: Check creatine kinase levels if muscle symptoms are severe or persistent

When to Refer to Specialist

• Severe muscle pain with elevated creatine kinase levels
• Symptoms suggestive of inflammatory myositis (proximal muscle weakness rather than just pain) 1
• Failure to achieve LDL-C goals despite multiple medication trials
• Suspected autoimmune reaction to PCSK9 inhibitors

Remember that muscle symptoms are often subjective and may be influenced by patient awareness of potential side effects. A supportive approach while ensuring adequate lipid-lowering therapy is maintained is essential for cardiovascular risk reduction.