What are the alternative treatments to lower cholesterol for a patient who cannot take statin (HMG-CoA reductase inhibitor)?

From the Guidelines

For patients who cannot take statins, the primary alternative to lower cholesterol is ezetimibe (Zetia), typically prescribed at 10 mg once daily, as it has been shown to be effective in reducing LDL cholesterol levels by 18% as monotherapy and 25% when added to statin therapy 1. Other options include:

• PCSK9 inhibitors (evolocumab or alirocumab), given as subcutaneous injections every 2-4 weeks, which have been demonstrated to significantly reduce LDL cholesterol levels and major adverse cardiovascular events when added to maximum-tolerated statin 1.
• Bile acid sequestrants like cholestyramine or colesevelam, taken orally 1-2 times daily, which can be effective in lowering LDL cholesterol levels, especially in patients who do not tolerate statins 1.
• Fibrates such as fenofibrate, usually 145 mg daily, which primarily lower triglycerides but can also have a modest effect on LDL cholesterol levels.
• Niacin, starting at 500 mg daily and gradually increasing to 1-2 g daily, which affects lipid metabolism in multiple ways but may have limited efficacy in reducing LDL cholesterol levels compared to other options.

In addition to medication, lifestyle modifications are crucial:

• Follow a low-cholesterol, heart-healthy diet
• Exercise regularly (aim for 150 minutes of moderate-intensity exercise per week)
• Maintain a healthy weight
• Quit smoking if applicable These alternatives work through different mechanisms than statins, and combining these approaches with lifestyle changes can effectively manage cholesterol levels in statin-intolerant patients. It is essential to note that the choice of alternative therapy should be individualized based on the patient's specific needs and medical history, and the most recent and highest-quality evidence should be considered when making treatment decisions 1.

From the FDA Drug Label

Ezetimibe tablets is a medicine used with a cholesterol lowering diet: and with other cholesterol medicines called a statin, or alone (when additional cholesterol lowering treatments are not possible), to lower elevated low-density lipoprotein cholesterol (LDL-C) or bad cholesterol in adults with primary hyperlipidemia 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

Alternative treatments to lower cholesterol for a patient who cannot take statin (HMG-CoA reductase inhibitor) include:

• Ezetimibe: a medicine used to lower elevated low-density lipoprotein cholesterol (LDL-C) or bad cholesterol in adults with primary hyperlipidemia, which can be used alone when additional cholesterol lowering treatments are not possible 2
• Cholestyramine: a medicine used 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 3

From the Research

Alternative Treatments for Lowering Cholesterol

For patients who cannot take statin (HMG-CoA reductase inhibitor), several alternative treatments are available:

• Ezetimibe: a cholesterol absorption inhibitor that can be used as monotherapy or in combination with a low-dose statin 4, 5, 6, 7
• Bile acid sequestrants: can be used as an alternative to statins, although they may be less effective in reducing LDL cholesterol 4
• PCSK9 inhibitors: such as alirocumab and evolocumab, which can significantly reduce LDL cholesterol levels and ASCVD risk when added to maximally tolerated statin therapy or used as monotherapy 5, 6, 7
• Lipoprotein apheresis: may be considered for high-risk patients with multiple cardiovascular events and sub-optimal LDL cholesterol despite lipid-lowering drug therapy 4
• Bempedoic acid: a new therapeutic option that can be used in combination with a low-dose statin or as monotherapy 8

Comparison of Alternative Treatments

Studies have compared the efficacy of different alternative treatments:

• PCSK9 inhibitors have been shown to be more effective than ezetimibe in reducing LDL cholesterol levels in statin-intolerant patients 5, 6
• Alirocumab has been shown to produce greater LDL-C reductions than ezetimibe in statin-intolerant patients, with fewer skeletal-muscle adverse events compared to atorvastatin 6
• Ezetimibe has been shown to be effective in reducing LDL cholesterol levels and ASCVD risk when added to statin therapy or used as monotherapy, although it may not be as effective as PCSK9 inhibitors 5, 6, 7