Beyond Statins
What You Need to Know About Other LDL Cholesterol-Lowering TreatmentsWhat are Non-Statin Therapies?
Statins don’t work for everyone. In some cases, a statin by itself won’t lower your low-density lipoprotein (LDL) cholesterol – and in turn your atherosclerotic cardiovascular disease (ASCVD) risk – enough. In other cases, someone might not be able to take a statin.
When this happens, other medications – called non-statin therapies – offer more treatment options. Often, a non-statin will be added to a statin.
- If you are already on a statin at the highest dose you can take, but could still benefit from lowering your LDL cholesterol even more.
- In the rare case that you’re unable to take or tolerate a statin.
Non-Statin Therapies for Lowering LDL
| Non-statin treatment | How it lowers LDL cholesterol | How it’s taken | Side effects to be aware of * | Added ASVCD risk reduction |
| Ezetimibe | Works by blocking the body's ability to absorb cholesterol in the gut | By mouth, usually once daily | Diarrhea, stomach pain, muscle or joint pain, runny or stuffy nose, feeling tired | In some patients, adding ezetimibe to statin therapy lowered cardiovascular events. |
| Bempedoic acid | Partly blocks the production of cholesterol in the liver | By mouth, once daily | Muscle spasms, back pain, cold or flu-like symptoms, stomach pain, pain in hands or feet, signs of gout (swollen, red, tender joints, especially in the toes), tendon pain or swelling | Lowers cardiovascular risk in patients at risk for cardiovascular disease events who cannot take statin therapy. |
| PCSK9 inhibitors | Works by helping the body get rid of LDL cholesterol from the blood by blocking a protein in the liver (called proprotein convertase subtilisin kexin 9, or PCSK9) | Given under the skin by injection, 1-2 times a month | Skin reactions at the site of injection, allergic reactions, headache, muscle aches and spasms, cough, sinusitis (stuffy nose) | In some patients, adding a PCSK9 inhibitor to statin therapy (with or without ezetimibe) lowered cardiovascular events. |
| Inclisiran – also targets PSCK9, but in a different way | Stops PCSK9 from being produced in the liver. | Given under the skin 2 times a year – every 6 months after two initial doses | Pain, redness, or rash at the site of infection, joint pain, urinary tract infection, diarrhea, chest cold, pain in legs or arms, shortness of breath | When added to statin therapy, inclisiran cuts LDL cholesterol by more than half. |
* These are just some of the possible side effects. Always be sure to read the package insert that comes with your medication for a full list of side effects and other instructions.
Other lipid lowering medications are available that address other forms of lipid disorders.
When are Non-Statin Therapies Recommended?
Non-statin therapies may be recommended if:
• Your blood cholesterol remains high or you don’t see the drop in LDL cholesterol expected, despite being on the right dose of a statin (called maximally tolerated statin therapy).
Your health care team wants
to lower your ASCVD risk more—helping to prevent a stroke or heart attack.
• You can’t take a statin for some reason, either due to
side effects or a certain drug-drug interaction.
• You have familial hypercholesterolemia, or FH,
a disorder passed down in families that results in very high levels of LDL cholesterol and cardiovascular disease at early ages. Learn more about treatments for FH.
• Other factors, such as your preference for treatment and cost, may also come into play.
How Much Might It Lower My Cholesterol?
It depends. Studies suggest ezetimibe and PCSK9 inhibitors can lower cholesterol and, in turn, cardiovascular disease risk. Often, a non-statin is taken with a statin for additive effect, meaning both medications work together to give you the maximum benefit.
Your health care team may have already talked with you about how a risk calculator can be used to find your risk of developing ASCVD or having a heart attack or stroke. This calculator factors in things like:
- Age
- Sex
- Race
- Cholesterol
- Systolic blood pressure (the top number)
- If you smoke
- If you have diabetes
Your care team may also consider other factors that play a role or affect your risk.
Because your risk can change over time, it’s important to keep talking with your health care team about what steps you can take to stay healthy as you age.
Keep in mind that making lifestyle changes – in addition to taking a statin
or other medication – can help protect your heart and improve your overall health.
There are a number of things you might want to consider and talk with your health care team about as you think about whether to add a non-statin therapy.
- First, are you on the most potent and highest amount (dose) of such statin you can take already?
- How well have you managed to make lifestyle changes, including eating heart healthier and getting regular physical activity?
- What is your personal risk of ASCVD, and how much more would a non-statin lower that risk beyond what has been achieved on a statin alone?
- Possible drug-drug interactions, especially if you have other health issues.
- What you prefer for treatment once you know or understand your risk.
It is important to have your cholesterol levels tested again. This is often done:
- At the start of treatment
- 4-12 weeks after starting or changing a statin or other LDL cholesterol-lowering therapy
- At set times after that based on your care team's advice (usually 3-12 months)
As with starting any medication, talk with your health care team, share concerns and ask questions. For example, you might ask:
- Why are you recommending this treatment?
- How much more will it lower my cholesterol and my risk for a heart attack or stroke?
- How will we know if the medication is working?
- Are there certain side effects I should watch for? What should I do if I notice any?
- How often do I need to have my cholesterol checked?
- What else can I be doing to lower my chances of having a stroke or heart attack?
- Will my insurance cover it, especially the more costly, newer drugs?
- How is the medication given (by mouth, injection or infusion)?
- Statins are the first treatment for lowering high cholesterol and, in turn, reducing someone’s chance of having or dying from a heart attack or stroke
- Statins by themselves may not lower cholesterol enough effect for every person
- Cholesterol-lowering medications – regardless of which one – work best when coupled with a heart-healthy eating plan, regular exercise and other healthy habits.
Always feel free to ask your health care team questions. When doing your own research, rely on sources of information that you can trust. Besides CardioSmart, some examples:
Centers for Disease Control and PreventionCDC.gov/cholesterol/materials_for_patients.htm
2017 Focused Update of the 2016 ACC Expert Consensus Decision Pathway on the Role of Non-Statin Therapies for LDL-Cholesterol Lowering in the Management of Atherosclerotic Cardiovascular Disease Risk
A Report of the American College of Cardiology Task Force on Expert Consensus Decision Pathways
How Can I Find Out More
Always feel free to ask your health care team questions. When doing your own research, rely on sources of information that you can trust. Besides CardioSmart, some examples:
Centers for Disease Control and PreventionCDC.gov/cholesterol/materials_for_patients.htm
2022 ACC Expert Consensus Decision Pathway on the Role of Nonstatin Therapies for LDL-Cholesterol Lowering in the Management of Atherosclerotic Cardiovascular Disease Risk
A Report of the American College of Cardiology Task Force on Expert Consensus Decision Pathways
- Last Edited 08/25/2023