What is a cheaper alternative to Repatha (evolocumab) for a patient with hypercholesterolemia who is allergic to statins (HMG-CoA reductase inhibitors)?

Recommended Alternative to Repatha for Statin-Allergic Patients

For a patient allergic to statins who is currently on Repatha and seeking a cheaper alternative, ezetimibe is the most appropriate first-line option, providing 18-20% LDL-C reduction as monotherapy with an excellent safety profile and significantly lower cost. 1, 2

Primary Recommendation: Ezetimibe

Ezetimibe should be initiated at 10 mg daily as the cornerstone therapy for this statin-intolerant patient. 1, 3

• Ezetimibe inhibits cholesterol absorption in the small intestine through the NPC1L1 protein, achieving approximately 18-20% LDL-C reduction as monotherapy 1, 2, 3
• The drug is well-tolerated with common side effects limited to upper respiratory tract infection, diarrhea, arthralgia, sinusitis, and pain in extremities—notably without the muscle symptoms associated with statins 2, 3
• Clinical trial data from IMPROVE-IT demonstrated cardiovascular event reduction in secondary prevention settings, validating ezetimibe's clinical benefit beyond LDL-C lowering 1

If Additional LDL-C Lowering is Required

If ezetimibe monotherapy fails to achieve adequate LDL-C control, add a bile acid sequestrant (colesevelam 3.8-4.5 g daily) for an additional 15-18% LDL-C reduction. 2, 4

• Colesevelam (Welchol) provides 15-18% LDL-C reduction when used as monotherapy and can be combined with ezetimibe for additive effects 4
• The drug binds bile acids in the intestine, promoting hepatic conversion of cholesterol to bile acids 2
• Important caveat: Bile acid sequestrants cause gastrointestinal side effects (constipation, bloating) and have multiple drug-drug interactions requiring careful timing of other medications 2, 4
• Colesevelam should be taken with meals and other medications should be administered at least 4 hours before or after colesevelam to avoid binding interactions 4

Emerging Alternative: Bempedoic Acid

Bempedoic acid (Nexletol) represents a newer non-statin option that can be considered, particularly if ezetimibe alone is insufficient. 2, 5

• Bempedoic acid inhibits ATP citrate lyase, reducing cholesterol synthesis upstream of the statin pathway, making it suitable for statin-intolerant patients 2
• The drug has an excellent safety profile without skeletal muscle symptoms or increased diabetes risk 5
• Key consideration: Bempedoic acid causes a small increase in plasma uric acid and slightly increased frequency of gout episodes in susceptible patients 5

When PCSK9 Inhibitors Remain Necessary

If the patient has very high cardiovascular risk (multiple major ASCVD events or one major event plus multiple high-risk conditions) and LDL-C remains ≥70 mg/dL on ezetimibe, alirocumab (Praluent) is the direct PCSK9 inhibitor alternative to Repatha. 2, 6

• Alirocumab provides 45-58% LDL-C reduction with similar efficacy, safety profile, and mechanism of action as evolocumab 2
• The ODYSSEY Outcomes trial demonstrated cardiovascular event reduction comparable to the FOURIER trial with evolocumab 1, 2
• Both PCSK9 inhibitors are injectable medications with similar cost structures, so switching between them may not provide significant cost savings 2

Cost-Effectiveness Algorithm

Follow this stepwise approach prioritizing cost and efficacy:

1. Start with ezetimibe 10 mg daily (lowest cost, oral administration, proven CV benefit) 1, 2
2. If LDL-C remains elevated, add colesevelam 3.8 g daily (moderate cost increase, additive LDL-C lowering) 2, 4
3. Consider bempedoic acid if combination therapy with ezetimibe and bile acid sequestrant is not tolerated or insufficient 2, 5
4. Reserve PCSK9 inhibitors (alirocumab or continue evolocumab) only for very high-risk patients who fail to achieve LDL-C <70 mg/dL on maximal non-statin therapy 1, 2, 6

Critical Monitoring Points

• Assess LDL-C levels 4 weeks after initiating or changing therapy to evaluate response 1, 6
• Verify medication adherence before escalating therapy, as non-adherence is a common cause of treatment failure 1
• For patients with established ASCVD, target LDL-C <70 mg/dL; for very high-risk patients, target <55 mg/dL 1, 6
• Monitor for gout symptoms if using bempedoic acid, particularly in patients with history of hyperuricemia 5

Common Pitfall to Avoid

Do not assume all "statin allergy" is true immunologic hypersensitivity. 7 Many patients labeled as statin-intolerant have experienced muscle symptoms that may be dose-related or specific to certain statins. However, since this patient is described as "allergic to statin," proceed with non-statin alternatives as outlined above rather than attempting statin rechallenge. 1, 7