What alternative can be used for a patient who cannot tolerate Ezetimibe (Zetia)?

From the Guidelines

If your patient can't tolerate Zetia (ezetimibe), the most suitable alternative cholesterol-lowering option is bempedoic acid (180mg daily), as it has been shown to reduce LDL-C levels by 15% to 25% with low rates of muscle-related adverse effects 1. When considering alternatives to Zetia, it's essential to evaluate the patient's specific cholesterol issues, cardiovascular risk factors, and the reason for Zetia intolerance.

• Bempedoic acid inhibits ATP-citrate lyase, reducing cholesterol synthesis upstream from statins, and has been demonstrated to be safe and well-tolerated in statin-intolerant patients 1.
• PCSK9 inhibitors, such as evolocumab (140mg subcutaneously every 2 weeks) or alirocumab (75-150mg subcutaneously every 2 weeks), are also viable options, as they increase LDL receptor recycling, dramatically lowering LDL levels 1.
• Bile acid sequestrants like cholestyramine (8-16g daily) or colesevelam (3.75g daily) may also be considered, as they work by binding bile acids in the intestine, preventing reabsorption and forcing the liver to use cholesterol to make more bile acids. It's crucial to address lifestyle modifications, including diet, exercise, and weight management, as foundational approaches to managing cholesterol levels.
• Combination therapy with statins may be considered if appropriate, but it's essential to weigh the benefits and risks of each treatment option and select the most suitable one for the patient's specific needs. The CLEAR Outcomes trial demonstrated that bempedoic acid reduced MACE by 13% in statin-intolerant patients, making it a promising alternative for patients who cannot tolerate Zetia 1.

From the Research

Alternative Options to Zetia

If a patient cannot tolerate Zetia (ezetimibe), there are other alternatives that can be considered for lowering low-density lipoprotein cholesterol (LDL-C) levels.

• Bile acid sequestrants (BAS) such as cholestyramine, colestipol, or colesevelam can be used as an alternative to ezetimibe 2.
• These agents work by binding to bile acids in the intestine and preventing their reabsorption, which in turn reduces the amount of cholesterol produced in the liver.
• Colesevelam, in particular, has been shown to have a greater specificity for bile acids and fewer drug interactions compared to older BAS agents 2.

Considerations for Alternative Therapies

When considering alternative therapies to ezetimibe, it is essential to evaluate the patient's individual needs and medical history.

• For example, if the patient is already taking a statin, the addition of a BAS may be considered, as the combination of these two types of drugs has been shown to be effective in reducing LDL-C levels 3.
• However, it is crucial to monitor the patient's liver enzyme levels and adjust the treatment plan as needed, as the coadministration of ezetimibe and statins may increase the risk of elevated liver transaminase levels 2.

Safety Profiles of Alternative Therapies

The safety profiles of alternative therapies to ezetimibe, such as BAS, have been well-established in clinical trials.

• These agents have been shown to be systemically safe, with minimal risk of myopathy or rhabdomyolysis 2.
• However, BAS may cause gastrointestinal side effects, such as constipation, and may increase plasma triglyceride levels due to the alteration of hepatic lipid metabolism 2.