From the Guidelines
Ezetimibe (Zetia) is a good first-line alternative to statins for managing cholesterol, as it works by blocking cholesterol absorption in the intestine rather than affecting muscle tissue, and is typically prescribed at 10mg once daily 1. When considering alternatives to statins due to muscle, joint, and tendon side effects, several options are available.
- Ezetimibe, as mentioned, is a first-line choice, providing an 18% reduction in LDL-C when used as monotherapy and a 25% reduction when combined with statin therapy 1.
- PCSK9 inhibitors like evolocumab (Repatha) and alirocumab (Praluent) are powerful options, given as injections every 2-4 weeks, offering significant cholesterol reduction with minimal muscle-related side effects 1.
- Bempedoic acid (Nexletol), taken as a 180mg daily tablet, works earlier in the cholesterol production pathway than statins, reducing muscle-related side effects 1.
- Bile acid sequestrants such as cholestyramine or colesevelam can be effective but may cause gastrointestinal discomfort 1. For those preferring natural approaches,
- plant sterols/stanols (2 grams daily)
- soluble fiber (5-10 grams daily)
- and red yeast rice supplements may help, though the latter should be used cautiously as it contains natural statin-like compounds 1. Any medication change should be discussed with a healthcare provider, as the appropriate alternative depends on your specific health situation, cholesterol levels, and cardiovascular risk factors 1.
From the FDA Drug Label
The FDA drug label does not answer the question.
From the Research
Alternatives to Statins
To avoid tendon, muscle, and joint side effects associated with statins, several alternative treatments can be considered:
- Ezetimibe: a cholesterol absorption inhibitor that can be used individually or in combination with statins to lower low-density lipoprotein cholesterol (LDL-C) levels 2, 3, 4, 5
- Bile acid sequestrants: can be used individually or in combination with statins to lower LDL-C levels 2, 3, 5
- Fibrates: can be used to modulate lipid metabolism and improve the ratio of high-density to low-density lipoproteins 3, 4
- PCSK9 inhibitors: a newly discovered therapy that can be used to reduce plasma cholesterol levels 4
Mechanisms and Efficacy
These alternative treatments have different mechanisms of action and efficacy:
- Ezetimibe and bile acid sequestrants interrupt the enterohepatic circulation of bile salts and inhibit cholesterol absorption 5
- Fibrates modulate lipid metabolism and improve the ratio of high-density to low-density lipoproteins 4
- PCSK9 inhibitors reduce plasma cholesterol levels by virtue of their effects on synthesis, reuptake, and intestinal absorption of cholesterol 4
Considerations
When considering alternative treatments to statins, it is essential to weigh the benefits and risks:
- While statins are generally well-tolerated, muscle symptoms are often reported, and exchange of statin or reduction of dose may be beneficial in some cases 6
- The efficacy of combination therapy of statins with ezetimibe or bile acid sequestrants for the prevention of cardiovascular disease remains to be confirmed in clinical endpoint studies 5