From the Guidelines
For lowering cholesterol without muscle aches, ezetimibe (brand name Zetia) is often the best alternative to statins, as it works differently by blocking cholesterol absorption in the intestines rather than inhibiting cholesterol production in the liver, which is why it typically doesn't cause muscle pain, with a standard dose of 10 mg once daily, taken with or without food, and can lower LDL cholesterol by 15-20% when used alone, as supported by the most recent study 1.
Key Points to Consider:
- Ezetimibe is a non-statin medication that can be used to lower LDL cholesterol without causing muscle pain, with a mean percentage reduction in LDL-C of 18% when used as monotherapy and 25% when used in combination with statin therapy, as noted in 1.
- Other options for lowering cholesterol without muscle aches include bile acid sequestrants like cholestyramine or colesevelam, which bind to bile acids in the intestines and prevent reabsorption, indirectly reducing cholesterol levels, as mentioned in 1.
- PCSK9 inhibitors (evolocumab, alirocumab) are injectable medications that can dramatically lower cholesterol without muscle side effects, though they're typically reserved for people with very high cholesterol or those who can't tolerate other medications due to their cost, as discussed in 1.
- Plant stanols/sterols found in certain margarines and supplements can also help lower cholesterol by blocking absorption, as noted in 1.
- Before switching medications, it's essential to discuss with your doctor, as they may suggest trying a different statin at a lower dose or alternate-day dosing to minimize muscle symptoms while still getting cholesterol-lowering benefits, as recommended in 1.
Recent Study Findings:
- A recent study published in 2025 1 found that bempedoic acid, a novel LDL cholesterol-lowering agent, can lower LDL cholesterol levels by 15% for those on statins and 24% for those not taking statins, with an additional 19% reduction in LDL cholesterol when used with ezetimibe.
- The study also found that bempedoic acid can reduce the risk of major adverse cardiovascular events by 13% compared with placebo for individuals with established ASCVD or at high risk for ASCVD considered to be intolerant to statin therapy.
From the Research
Effective Medication for Lowering Cholesterol without Myalgia
- Ezetimibe is a selective cholesterol absorption inhibitor that has been shown to lower low-density lipoprotein cholesterol (LDL-C) by approximately 15 to 20% when used as monotherapy or in combination with statins or fenofibrate 2, 3, 4.
- Unlike other lipid-lowering medications, ezetimibe does not appear to worsen hypertriglyceridemia and has an adverse-event profile similar to placebo when used as monotherapy or in combination with statins 2, 3.
- Ezetimibe has been found to have a favorable pharmacokinetic profile, allowing it to be administered once daily and given in conjunction with statins 4, 5.
- The combination of ezetimibe with a statin has been shown to be more effective than statin monotherapy in lowering LDL-cholesterol and improving other lipid parameters, with a safety profile comparable to that of statin monotherapy 4, 6.
Mechanism of Action and Benefits
- Ezetimibe works by blocking the intestinal absorption of both biliary and dietary cholesterol, specifically by inhibiting the intestinal sterol transporters, Niemann-Pick C1-like 1 proteins 6, 5.
- In addition to lowering LDL-cholesterol, ezetimibe may also favorably affect other parameters, such as raising high-density lipoprotein cholesterol (HDL-C) and lowering levels of triglycerides, non-HDL-cholesterol, apolipoprotein B, and remnant-like particle cholesterol 6.
- Ezetimibe has been found to have an excellent safety and tolerability profile, making it an attractive adjunct therapy for the treatment of hypercholesterolemia 5.