What are the treatment options for a patient with hypercholesterolemia (elevated total cholesterol of 312 mg/dL) and high low-density lipoprotein (LDL) (196 mg/dL) who is averse to statin (HMG-CoA reductase inhibitor) therapy?

From the Guidelines

For a patient with significantly elevated total cholesterol (312) and LDL (196) who is averse to statins, I recommend starting with a non-statin medication like ezetimibe 10mg daily, combined with intensive lifestyle modifications. This approach is based on the principles outlined in the National Cholesterol Education Program Adult Treatment Panel III guidelines 1, which emphasize the importance of therapeutic lifestyle changes (TLC) and LDL-lowering therapy in managing patients with high cholesterol. Given the patient's high LDL levels, the goal is to achieve an LDL-C level < 100 mg/dL, with a therapeutic option of < 70 mg/dL for those at very high risk 1. Key components of TLC include:

• A Mediterranean or DASH diet
• Regular exercise (150 minutes weekly of moderate activity)
• Weight management if needed
• Smoking cessation
• Limiting alcohol consumption If ezetimibe alone is insufficient, adding a PCSK9 inhibitor such as evolocumab (140mg subcutaneously every 2 weeks) or alirocumab (75-150mg subcutaneously every 2 weeks) can dramatically lower LDL levels. Bempedoic acid (180mg daily) is another non-statin option that works upstream from statins in the cholesterol synthesis pathway and may cause fewer muscle-related side effects. Bile acid sequestrants like cholestyramine or colesevelam can also be considered but often have gastrointestinal side effects. Regular monitoring of lipid levels every 3-6 months is essential to assess treatment efficacy and adjust therapy as needed. It's also important to understand why the patient is averse to statins—if it's due to previous side effects, a different statin at a lower dose or alternate-day dosing might still be tolerable. Ultimately, the treatment plan should be individualized based on the patient's specific risk factors, medical history, and preferences.

From the FDA Drug Label

Cholestyramine for Oral Suspension, USP powder is indicated as adjunctive therapy to diet for the reduction of elevated serum cholesterol in patients with primary hypercholesterolemia (elevated low density lipoprotein [LDL] cholesterol) who do not respond adequately to diet 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

For a patient with hypercholesterolemia (elevated total cholesterol of 312 mg/dL) and high low-density lipoprotein (LDL) (196 mg/dL) who is averse to statin (HMG-CoA reductase inhibitor) therapy, treatment options include:

• Ezetimibe: a medication that can be used alone or in combination with other lipid-lowering agents, such as fenofibrate, to lower total cholesterol and LDL-C levels.
• Cholestyramine: a bile acid sequestrant that can be used as adjunctive therapy to diet for the reduction of elevated serum cholesterol in patients with primary hypercholesterolemia.
• Fenofibrate: a fibric acid derivative that can be used alone or in combination with ezetimibe to lower total cholesterol, LDL-C, Apo B, and non-HDL-C levels. It is essential to note that these treatment options should be used under the guidance of a healthcare professional and in conjunction with dietary therapy and lifestyle modifications. 2 3

From the Research

Treatment Options for Hypercholesterolemia

For a patient with elevated total cholesterol (312 mg/dL) and high low-density lipoprotein (LDL) (196 mg/dL) who is averse to statin therapy, several alternative treatment options are available:

• Ezetimibe, a cholesterol absorption inhibitor, can be used as monotherapy or in combination with other lipid-lowering agents 4, 5
• Bile acid resins (BARs) or niacin can be used as adjunctive treatments to lower LDL-C levels 6, 7
• PCSK9 inhibitors, such as evolocumab or alirocumab, can be used to reduce LDL-C levels, especially in high-risk patients who are not achieving treatment goals on a maximum tolerated dose of a statin and ezetimibe 8
• Fenofibrate can be used to reduce triglycerides and cardiovascular risk in patients with type 2 diabetes when triglycerides are elevated and high-density lipoprotein (HDL) is low 5

Considerations for Treatment

When determining the optimal treatment regimen, several factors should be considered, including:

• The patient's baseline absolute cardiovascular risk, LDL-C level, and consensus LDL-C targets 6, 7
• The efficacy and safety data of any adjunctive treatment, along with drug costs and patient adherence to treatment 6, 4
• The potential for combination therapy to achieve LDL-C goals, while minimizing side effects and improving patient acceptance and adherence 6, 4, 5