What are alternative treatments for hyperlipidemia in patients intolerant to statins (HMG-CoA reductase inhibitors)?

From the Guidelines

For individuals intolerant to statins, the most effective alternative for cholesterol management is PCSK9 inhibitors, such as evolocumab or alirocumab, which can lower LDL cholesterol by 50-60%. These medications have been shown to be safe and well-tolerated in patients with statin intolerance, with fewer skeletal muscle-related adverse events compared to ezetimibe and atorvastatin 1. Other alternatives include ezetimibe, which can reduce LDL cholesterol by 15-20% by blocking intestinal cholesterol absorption, and bempedoic acid, a newer medication that offers 15-25% LDL reduction by inhibiting cholesterol synthesis earlier in the pathway than statins 1.

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

• The patient's individual risk factors for cardiovascular disease
• The presence of any comorbidities, such as diabetes or high triglycerides
• The patient's tolerance to potential side effects, such as muscle pain or gastrointestinal symptoms
• The potential for drug interactions with other medications the patient is taking

In terms of specific medications, the following options are available:

• PCSK9 inhibitors: evolocumab (Repatha) and alirocumab (Praluent), administered as subcutaneous injections every 2-4 weeks
• Ezetimibe (Zetia): taken as a 10mg daily oral tablet
• Bempedoic acid (Nexletol): a newer 180mg daily oral medication
• Bile acid sequestrants: such as cholestyramine or colesevelam, though less convenient due to multiple daily doses and gastrointestinal side effects
• Prescription omega-3 fatty acids: such as Vascepa or Lovaza, at 2-4g daily, for those with very high triglycerides

Additionally, lifestyle modifications remain crucial, including:

• Adopting a Mediterranean or DASH diet
• Regular exercise (150 minutes weekly)
• Weight management
• Smoking cessation
• Limiting alcohol consumption, which can collectively reduce cholesterol by 10-15% and provide additional cardiovascular benefits 1.

From the FDA Drug Label

The difference between REPATHA and placebo in mean percent change in LDL-C from baseline to Week 12 was −63% (95% CI: −63%, −62%) and from baseline to Week 72 was −57% (95% CI: −58%, −56%) The difference between REPATHA and placebo in mean percent change in LDL-C from baseline to Week 12 was −55% (95% CI: −60%, −50%; p < 0. 0001) and −57% (95% CI: −61%, −52%; p < 0.0001) for the 140 mg every 2 weeks and 420 mg once monthly dosages, respectively. The difference between REPATHA and ezetimibe in mean percent change in LDL-C from baseline to Week 12 was −45% (95% CI: −52%, −39%; p < 0. 0001) and −41% (95% CI: −47%, −35%; p < 0. 0001) for the 140 mg every 2 weeks and 420 mg once monthly dosages, respectively.

Evolocumab (REPATHA) is a good alternative to cholesterol management if intolerant to statins.

• It significantly reduces the risk of cardiovascular events, including cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization.
• It can be administered subcutaneously every 2 weeks or once monthly.
• The recommended dosage is 140 mg every 2 weeks or 420 mg once monthly.
• Evolocumab has been shown to be effective in reducing LDL-C levels in patients with hyperlipidemia, including those with heterozygous familial hypercholesterolemia (HeFH) 2, 2.

From the Research

Alternatives to Statins for Cholesterol Management

If a patient is intolerant to statins, there are several alternative treatment options available. These alternatives include:

• Ezetimibe: a medication that can be used individually or in combination with other treatments to lower low-density lipoprotein cholesterol (LDL-C) levels 3
• Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors: such as evolocumab, alirocumab, and inclisiran, which have shown an excellent safety profile and can be used to lower LDL-C levels 4, 5
• Bempedoic acid: a recently approved medication that can be used to lower LDL-C levels, although it may be associated with a small increase in plasma uric acid and slightly increased frequency of episodes of gout in susceptible subjects 4
• Angiopoietin-like 3 protein inhibitors: a new class of medications that may be useful in the treatment of hypercholesterolemia 6
• Nutraceuticals: dietary supplements that may be used in combination with other treatments to lower LDL-C levels 6

Considerations for Choosing an Alternative to Statins

When choosing an alternative to statins, several factors should be considered, including:

• The patient's individual needs and medical history
• The degree of LDL-C lowering required
• The potential side effects and interactions of the alternative treatment
• The cost and availability of the alternative treatment 4, 5
• The patient's ability to tolerate the alternative treatment, as some patients may experience muscle-related symptoms or other adverse effects 7