What alternative medication should be used for a patient with hyperlipidemia who has an allergy to statins (HMG-CoA reductase inhibitors)?

From the Guidelines

For patients with hyperlipidemia who have a statin allergy, I strongly recommend ezetimibe (10 mg daily) as the first-line alternative, as it has been shown to be effective in reducing LDL-C levels and improving cardiovascular outcomes, as demonstrated in the IMPROVE-IT trial 1.

Alternative Medication Options

Ezetimibe works by blocking intestinal cholesterol absorption rather than inhibiting cholesterol synthesis like statins, making it a suitable option for statin-allergic patients.

• The mechanism of action of ezetimibe involves inhibiting the NPC1L1 protein, which reduces cholesterol absorption in the small intestine.
• The FDA-approved indication for ezetimibe includes adjunct to diet to reduce TC, LDL-C, ApoB, and non-HDL-C in patients with primary hyperlipidemia, either alone or in combination with statin therapy.

Second-Line Options

PCSK9 inhibitors such as evolocumab (140 mg subcutaneously every 2 weeks) or alirocumab (75-150 mg subcutaneously every 2 weeks) are excellent second-line options, particularly for high-risk patients needing significant LDL reduction, as they have been shown to be effective in reducing LDL-C levels and improving cardiovascular outcomes, as demonstrated in the FOURIER trial 1.

• The mechanism of action of PCSK9 inhibitors involves binding to PCSK9 and increasing the number of LDL receptors available to clear circulating LDL-C.
• The FDA-approved indication for PCSK9 inhibitors includes adjunct to diet and maximally tolerated statin therapy to treat adults with HeFH or clinical ASCVD who need more LDL-C reduction.

Additional Considerations

Before starting any medication, it is essential to confirm the statin allergy through careful history or rechallenge under medical supervision, as some reactions may be non-allergic side effects that could be managed with a different statin or dosing regimen.

• Combination therapy is often necessary to achieve lipid goals, and patients with high triglycerides may benefit from fenofibrate (145 mg daily) or omega-3 fatty acids (2-4 g daily).
• Bile acid sequestrants like cholestyramine (4-16 g daily) or colesevelam (3.75 g daily) can also be effective but may cause gastrointestinal side effects.

From the FDA Drug Label

FENOFIBRATE The FDA drug label does not answer the question.

From the Research

Alternative Medications for Hyperlipidemia

For patients with hyperlipidemia who have an allergy to statins (HMG-CoA reductase inhibitors), several alternative medications can be considered:

• Ezetimibe: a viable option for patients who cannot tolerate statins 2, 3
• Bile acid sequestrants: such as colesevelam, which can reduce LDL-C levels by 16-22% in monotherapy and add a further 12-14% reduction in LDL-C when combined with other lipid-lowering drugs 4, 3
• PCSK9 inhibitors: may be used if LDL cholesterol targets are not reached with other medications 2, 5
• Lipoprotein apheresis: may be considered for high-risk patients with multiple cardio-vascular events and sub-optimal LDL cholesterol despite lipid-lowering drug therapy 2

Considerations for Alternative Medications

When selecting an alternative medication, the following factors should be considered:

• Efficacy: the ability of the medication to reduce LDL-C levels and achieve treatment goals
• Safety: the potential for adverse effects, such as gastrointestinal disease or high triglycerides, associated with certain medications 4
• Tolerability: the ability of the patient to tolerate the medication, including potential interactions with other medications 6, 5