What are alternative treatments for a patient experiencing side effects from statin (HMG-CoA reductase inhibitor) therapy?

From the Guidelines

For patients experiencing side effects from statins, the most effective alternative is to consider PCSK9 inhibitors like evolocumab (Repatha) and alirocumab (Praluent), or ezetimibe (Zetia), as these have been shown to significantly reduce LDL-C levels and ASCVD risk in patients who cannot tolerate statins 1.

Alternatives to Statins

When considering alternatives to statins, several options are available:

• PCSK9 inhibitors like evolocumab (Repatha) and alirocumab (Praluent) are effective options, typically administered as subcutaneous injections every 2-4 weeks, with a mechanism of action that increases the number of LDL receptors available to clear circulating LDL-C 1.
• Ezetimibe (Zetia), taken as a 10mg daily oral tablet, works by reducing intestinal cholesterol absorption and can lower LDL by 15-20% with minimal side effects, and has been shown to reduce ASCVD risk in patients with ACS 1.
• Bempedoic acid (Nexletol), a newer option taken as a 180mg daily oral tablet, inhibits cholesterol synthesis earlier in the pathway than statins.
• Bile acid sequestrants such as cholestyramine or colesevelam can reduce LDL by 15-30% but may cause gastrointestinal side effects.

Considerations for Alternative Therapies

When selecting an alternative to statins, consider the following:

• The specific side effects experienced by the patient
• The degree of LDL lowering needed
• The patient's cardiovascular risk profile
• The potential for drug-drug interactions
• The need for lifestyle modifications, including a Mediterranean or DASH diet, regular exercise, weight management, and smoking cessation

Recommendation

In patients with statin-associated side effects that are not severe, it is recommended to reassess and to rechallenge to achieve a maximal LDL-C lowering by modified dosing regimen, an alternate statin or in combination with nonstatin therapy, such as ezetimibe or PCSK9 inhibitors 1.

From the FDA Drug Label

5.1 Risks Associated with Combination Treatment with a Statin, Fenofibrate, or Other LDL-C Lowering Therapies 12.1 Mechanism of Action The patient having side effects from statin therapy may consider ezetimibe as an alternative. Ezetimibe works by inhibiting the intestinal absorption of cholesterol, which can help lower LDL-C levels.

• Key benefits:
  • Does not have the same side effect profile as statins
  • Can be used as monotherapy or in combination with other LDL-C lowering therapies
  • May be a suitable option for patients who cannot tolerate statins due to side effects 2

From the Research

Alternatives to Statins

For patients experiencing side effects from statins, several alternative treatments are available. These alternatives include:

• Ezetimibe, a cholesterol absorption inhibitor
• Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, such as evolocumab and alirocumab
• Bempedoic acid, a recently approved treatment for hypercholesterolemia
• Fibrates and nutraceuticals, which can be used in combination with other therapies or as standalone treatments 3, 4, 5

Safety and Efficacy of Alternatives

Studies have shown that these alternative treatments have an excellent safety profile and are not associated with the same side effects as statins, such as skeletal muscle symptoms or increased risk of new-onset diabetes 3, 4. However, PCSK9 inhibitors may be associated with injection site reactions, and bempedoic acid may increase plasma uric acid levels and the frequency of gout episodes in susceptible individuals 3.

Treatment Strategies

For patients with statin-associated side effects, treatment strategies may involve:

• Modifying the statin regimen or switching to a different statin
• Adding a non-statin lipid-lowering agent, such as ezetimibe or a PCSK9 inhibitor, to the treatment regimen
• Using alternative therapies, such as fibrates or nutraceuticals, as standalone treatments or in combination with other therapies 6, 5, 7

Benefits and Drawbacks of Alternatives

The benefits and drawbacks of using statins and non-statin lipid-lowering agents in patients with carotid artery disease have been summarized in recent studies 7. While statins and PCSK9 inhibitors have been shown to have significant cerebrovascular and cardiovascular benefits, they may also be associated with side effects. Ezetimibe and fibrates may have smaller reductions in stroke rates, but are still effective treatments for lowering LDL-C levels. Ultimately, the choice of treatment will depend on the individual patient's needs and medical history.