What are the alternatives to statins (HMG-CoA reductase inhibitors) for patients who cannot tolerate them?

From the Guidelines

For patients who cannot tolerate statins, the most effective alternative is to use PCSK9 inhibitors, such as evolocumab or alirocumab, which can lower LDL cholesterol by 50-60%. According to the most recent and highest quality study 1, PCSK9 inhibitors have been demonstrated to be safe and well-tolerated and improve lipid parameters in statin-intolerant patients. Other alternatives include ezetimibe (10mg daily), which blocks intestinal cholesterol absorption and reduces LDL by 15-20% with minimal side effects, and bempedoic acid (180mg daily), which works similarly to statins but with fewer muscle-related side effects, reducing LDL by 15-25%.

Some key points to consider when choosing an alternative to statins include:

• The patient's individual risk factors and medical history
• The potential benefits and risks of each alternative medication
• The patient's ability to tolerate and adhere to the chosen medication
• The need for regular monitoring and follow-up to assess the effectiveness of the chosen medication and adjust the treatment plan as needed.

It's also important to note that the choice of alternative medication may depend on the specific reason for statin intolerance, such as muscle pain or liver function abnormalities. In general, PCSK9 inhibitors are a good option for patients who cannot tolerate statins due to their high efficacy and safety profile 1. Additionally, ezetimibe and bempedoic acid may be considered as alternative options, especially for patients who are unable to tolerate PCSK9 inhibitors or have specific medical conditions that make these medications more suitable.

In terms of specific medications, the following options may be considered:

• Ezetimibe (10mg daily) for patients who require a moderate reduction in LDL cholesterol
• Bempedoic acid (180mg daily) for patients who require a moderate reduction in LDL cholesterol and have a high risk of cardiovascular disease
• PCSK9 inhibitors (evolocumab or alirocumab) for patients who require a high reduction in LDL cholesterol and have a high risk of cardiovascular disease.

Overall, the choice of alternative medication should be individualized based on the patient's specific needs and medical history, and should be guided by the most recent and highest quality evidence 1.

From the FDA Drug Label

Ezetimibe Tablet reduces total-C, LDL-C, Apo B, and non-HDL-C in patients with hyperlipidemia. Fenofibrate is used as an adjunct to diet to reduce low-density lipoprotein cholesterol (LDL-C), total cholesterol, triglycerides, and apolipoprotein B, and to increase high-density lipoprotein cholesterol (HDL-C) in adult patients with primary hypercholesterolemia or mixed dyslipidemia.

Alternatives to Statins:

• Ezetimibe: can be used to reduce LDL-C, total-C, Apo B, and non-HDL-C in patients with hyperlipidemia.
• Fenofibrate: can be used as an adjunct to diet to reduce LDL-C, total cholesterol, triglycerides, and apolipoprotein B, and to increase HDL-C in adult patients with primary hypercholesterolemia or mixed dyslipidemia.

These alternatives may be considered for patients who cannot tolerate statins. However, the choice of alternative therapy should be based on individual patient needs and medical history. 2 3

From the Research

Alternatives to Statins

For patients who cannot tolerate statins, several alternatives can be considered:

• Ezetimibe, a selective cholesterol absorption inhibitor, can be used as monotherapy or in combination with statins 4, 5, 6, 7
• Combination therapy with ezetimibe and a statin can provide additional reductions in LDL-C, facilitating the achievement of target goals 5, 7
• Lower-intensity statin combined with nonstatin medication, such as ezetimibe, may be an alternative for patients who do not tolerate or respond to high-intensity statin monotherapy 8

Mechanism of Action

Ezetimibe works by inhibiting the absorption of biliary and dietary cholesterol from the small intestine, without affecting the absorption of fat-soluble vitamins, triglycerides, or bile acids 4

• Ezetimibe localizes at the brush border of the small intestine and decreases cholesterol uptake into the enterocytes 4
• Combination therapy with ezetimibe and a statin provides dual inhibition of both cholesterol production and absorption, resulting in consistently greater reductions in LDL-C 7

Efficacy and Safety

Ezetimibe has been shown to be well tolerated and effective in lowering LDL-C, with a side-effect profile similar to that of placebo when given as monotherapy or in combination with statins 4, 5, 6

• Ezetimibe reduces LDL-C by 15-20% and increases high-density lipoprotein cholesterol by 2.5-5% when given as monotherapy or in combination with statins or fenofibrate 4
• Combination therapy with ezetimibe and a statin has been shown to be well tolerated and effective in lowering LDL-C and high-sensitivity C-reactive protein to target goals 5