What alternative treatment options are available for a patient with hyperlipidemia who is intolerant to statins (HMG-CoA reductase inhibitors) and Repatha (evolocumab)?

From the Guidelines

For patients who are intolerant to both statins and Repatha (evolocumab), consider prescribing ezetimibe 10 mg daily as a first-line alternative, as it has been demonstrated to be safe and well-tolerated, and improves lipid parameters in statin-intolerant patients 1. When considering alternatives to statins and Repatha, it's essential to evaluate the patient's individual needs and medical history.

• Ezetimibe works by inhibiting cholesterol absorption in the intestine, making it a viable option for patients who experience muscle-related side effects from statins.
• Bempedoic acid (Nexletol) 180 mg daily is another option that may cause fewer muscle-related side effects, as it works upstream of statins in the cholesterol synthesis pathway, and has been shown to reduce LDL-C levels by 15% to 25% 1.
• For patients needing more aggressive lipid lowering, consider combination therapy with ezetimibe plus bempedoic acid, which can be particularly effective in reducing LDL-C levels by approximately 35% 1.
• Lifestyle modifications, including a Mediterranean or plant-based diet, regular exercise, weight management, and smoking cessation, remain essential and should be implemented in conjunction with pharmacological treatment. It's crucial to note that while PCSK9 inhibitors other than Repatha, such as alirocumab (Praluent), might be tolerated despite intolerance to evolocumab, the most recent and highest quality study 1 supports the use of ezetimibe and bempedoic acid as safe and effective alternatives for patients with statin intolerance.

From the FDA Drug Label

Patients were randomized to receive placebo, ezetimibe tablet alone, 160 mg fenofibrate alone, or ezetimibe tablet and 160 mg fenofibrate in the 12-week trial. Ezetimibe Tablet coadministered with fenofibrate significantly lowered total-C, LDL-C, Apo B, and non-HDL-C compared to fenofibrate administered alone Ezetimibe tablet, administered with atorvastatin or simvastatin (40- and 80-mg statin groups, pooled), significantly reduced LDL-C (21%) compared with increasing the dose of simvastatin or atorvastatin monotherapy from 40 to 80 mg (7%).

For a patient who is statin and Repatha intolerant, consider the following options:

• Ezetimibe alone
• Ezetimibe coadministered with fenofibrate These options may help lower LDL-C levels. However, it is essential to consult the patient's medical history and current condition before making any clinical decisions 2.

From the Research

Treatment Options for Statin and Repatha Intolerant Patients

• For patients who are intolerant to statins and Repatha (evolocumab), alternative treatment options are available, including ezetimibe, bile acid sequestrants, and bempedoic acid 3, 4, 5.
• Ezetimibe can be used to lower LDL-C levels by reducing intestinal absorption of cholesterol, and it has been shown to be effective in combination with statins or as a monotherapy 3, 6, 5.
• Bempedoic acid is another option that reduces hepatic cholesterol synthesis and has been shown to be effective in lowering LDL-C levels 3.
• PCSK9 inhibitors, such as evolocumab, can also be used to lower LDL-C levels, but in this case, the patient is intolerant to Repatha, so other PCSK9 inhibitors may be considered 7.

Considerations for Treatment

• When selecting a treatment option, it is essential to consider the patient's individual needs and medical history, as well as the potential side effects and interactions of each medication 4, 6.
• The treatment goal should be to lower LDL-C levels to reduce the risk of major adverse cardiovascular events (MACE) 3, 6.
• Combination therapy may be necessary to achieve optimal LDL-C levels, and the choice of medications should be based on the patient's response to treatment and tolerance to side effects 3, 4, 5.

Alternative Therapies

• Lipoprotein apheresis may be considered for high-risk patients with multiple cardiovascular events and sub-optimal LDL-C levels despite lipid-lowering drug therapy 4.
• Other alternative therapies, such as bile acid sequestrants, may also be considered, but their efficacy and safety should be evaluated on a case-by-case basis 5.