Alternatives to Repatha for LDL Cholesterol Lowering
PCSK9 Inhibitor Alternative
- The American College of Cardiology recommends alirocumab (Praluent) as a direct alternative to Repatha (evolocumab) with similar efficacy, safety profile, and mechanism of action for lowering LDL cholesterol, reducing LDL-C by 45-58% when added to maximally tolerated statin therapy 1, 2
- Alirocumab's mechanism of action is a human monoclonal antibody to PCSK9 that binds to PCSK9 and increases the number of LDL receptors available to clear circulating LDL-C, with a safety profile that is generally well-tolerated with adverse effects including nasopharyngitis, injection site reactions, influenza, noncardiac chest pain, and myalgia 1, 2
Non-PCSK9 Inhibitor Alternatives
- Ezetimibe inhibits NPC1L1 protein in the small intestine, reducing cholesterol absorption, with efficacy of monotherapy reducing LDL-C by approximately 18%, and when combined with statin therapy, provides an additional 25% reduction, and is generally well-tolerated with common side effects including upper respiratory tract infection, diarrhea, arthralgia, sinusitis, and pain in extremities 3
- Bile acid sequestrants bind bile acids in the intestine, promoting hepatic conversion of cholesterol to bile acids, with efficacy of reducing LDL-C by 15-30%, and considerations of gastrointestinal side effects and interactions with other medications 4
- Bempedoic acid is a newer non-statin medication that inhibits ATP citrate lyase, reducing cholesterol synthesis, and can be used in statin-intolerant patients or as add-on therapy 5
Clinical Decision Algorithm
- The American College of Cardiology suggests that if PCSK9 inhibitors are not suitable, ezetimibe (oral medication, 18-25% LDL-C reduction) can be considered, and bile acid sequestrants can be added for additional LDL-C lowering 3, 4
- For statin-intolerant patients, consideration of combination of non-statin therapies for greater efficacy is recommended 5