Statins are a cornerstone of therapy for lowering high cholesterol, a major risk factor for cardiovascular disease [1.2.2]. However, not everyone can tolerate them due to side effects like muscle pain, or they may not be sufficient on their own [1.2.2, 1.10.2]. The worldwide prevalence of statin intolerance is estimated to be around 9.1%, prompting many to ask: what can be done instead of statins [1.10.1]? Fortunately, a range of alternatives, from lifestyle modifications to other classes of medication, is available.
The Foundation: Therapeutic Lifestyle Changes (TLC)
Before considering other medications, the first and most critical step is adopting heart-healthy lifestyle changes. The Therapeutic Lifestyle Changes (TLC) Program focuses on diet, physical activity, and weight management as a primary method to improve cholesterol numbers [1.4.1].
Key Lifestyle Modifications
- Dietary Adjustments: A heart-healthy diet involves reducing saturated and trans fats, which are known to raise LDL ("bad") cholesterol [1.4.2]. Increasing soluble fiber from sources like oats, beans, and fruits can help block cholesterol absorption [1.4.1]. Incorporating foods rich in unsaturated fats, such as avocados, nuts, and olive oil, is also beneficial [1.4.2].
- Regular Physical Activity: Exercise helps raise HDL ("good") cholesterol and can aid in weight management [1.4.4]. Adults should aim for at least 150 minutes of moderate-intensity exercise, like brisk walking or cycling, each week [1.4.2].
- Weight Management: Being overweight or obese can increase LDL cholesterol. Losing even a small amount of weight (5-10%) can significantly improve cholesterol levels [1.4.4].
- Quit Smoking and Limit Alcohol: Smoking damages blood vessels and lowers HDL cholesterol [1.4.4]. Excessive alcohol consumption can also raise cholesterol and triglyceride levels [1.4.2].
Prescription Non-Statin Medications
For individuals who need more than lifestyle changes, or for those with very high cholesterol (such as in familial hypercholesterolemia), several non-statin medications are effective alternatives [1.2.2].
Ezetimibe (Zetia)
Ezetimibe works by inhibiting the absorption of cholesterol from the small intestine [1.6.1, 1.3.3]. It can be used alone or in combination with a statin [1.6.5]. As a monotherapy, it can lower LDL cholesterol by about 18-20% [1.3.5, 1.6.4]. Common side effects include diarrhea and stomach pain [1.2.4].
PCSK9 Inhibitors (Praluent, Repatha)
Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are powerful injectable medications [1.2.3]. They work by increasing the liver's ability to remove LDL cholesterol from the blood [1.2.3, 1.7.3]. These drugs can lower LDL cholesterol by up to 60% and are often used for high-risk patients or those with familial hypercholesterolemia [1.2.2, 1.2.3]. They are administered as injections every two or four weeks [1.2.3]. Side effects may include injection site reactions and cold-like symptoms [1.2.2].
Bempedoic Acid (Nexletol)
Approved by the FDA in 2020, bempedoic acid is an oral medication that works in the liver to block cholesterol production through a different pathway than statins [1.5.1, 1.8.3]. It's particularly useful for statin-intolerant patients because it is not activated in skeletal muscle, reducing the risk of muscle-related side effects [1.8.3]. In clinical trials, it lowered LDL cholesterol by 17-28% and reduced major adverse cardiovascular events [1.8.3]. Side effects can include gout and elevated liver enzymes [1.8.3].
Bile Acid Sequestrants (Welchol, Colestid, Questran)
These are among the oldest cholesterol-lowering drugs [1.5.1]. They work in the intestines by binding to bile acids (which are made from cholesterol) and preventing their reabsorption [1.3.5]. This forces the liver to use more cholesterol to make new bile acids, lowering blood cholesterol levels [1.3.5]. However, they are generally less effective than newer agents and can cause gastrointestinal side effects like constipation, gas, and bloating [1.9.1, 1.9.5].
Comparison of Statin Alternatives
| Medication Class | Mechanism of Action | LDL Reduction | Common Side Effects |
|---|---|---|---|
| Ezetimibe | Inhibits cholesterol absorption in the small intestine [1.6.1]. | ~18-25% [1.3.5, 1.6.4] | Diarrhea, stomach pain, fatigue [1.2.2, 1.2.4]. |
| PCSK9 Inhibitors | Increases the number of LDL receptors in the liver to clear cholesterol from the blood [1.7.3]. | ~50-60% [1.2.2, 1.7.3] | Injection site reactions, flu-like symptoms, back pain [1.2.2]. |
| Bempedoic Acid | Blocks cholesterol synthesis in the liver via a different pathway than statins [1.8.3]. | ~17-28% [1.8.3] | Hyperuricemia (gout), muscle spasms, back pain, elevated liver enzymes [1.5.1, 1.8.3]. |
| Bile Acid Sequestrants | Binds to bile in the intestine, preventing its reabsorption and forcing cholesterol use [1.3.5]. | ~12-18% [1.3.5] | Constipation, bloating, gas, nausea [1.9.2, 1.9.5]. |
Dietary Supplements
Some people turn to supplements, but it is crucial to consult a healthcare provider, as their efficacy and safety vary. The FDA does not regulate supplements as strictly as prescription drugs [1.5.3].
- Red Yeast Rice: Contains monacolin K, a substance chemically identical to the statin drug lovastatin [1.5.3]. It can lower cholesterol but carries a similar risk of side effects as statins, including muscle pain and liver issues [1.5.3].
- Plant Sterols and Stanols: These compounds, found in plants, are added to some foods like fortified margarines [1.4.3]. They help block cholesterol absorption and can lower LDL cholesterol [1.4.1].
- Soluble Fiber (Psyllium): Supplements containing psyllium can effectively lower total and LDL cholesterol by helping to clear it from the blood [1.5.3].
Conclusion: An Individualized Approach to Cholesterol Management
For individuals wondering what can be done instead of statins, there are numerous effective strategies. The journey to lower cholesterol should always begin with foundational lifestyle changes [1.4.1]. When medication is necessary, a variety of non-statin prescriptions like ezetimibe, PCSK9 inhibitors, and bempedoic acid offer powerful alternatives tailored to different patient needs and risk levels [1.3.2]. These options allow for a personalized treatment plan developed in collaboration with a healthcare provider, ensuring both safety and effectiveness in the long-term management of cholesterol and the prevention of cardiovascular disease. Never stop or change medication without consulting your doctor.
