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Beyond Statins

What You Need to Know About Other LDL Cholesterol-Lowering Treatments

What 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.

Non-statin therapies should be considered and perhaps added:
  • 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 treatmentHow it lowers LDL cholesterol How it’s taken Side effects to be aware of *Added ASVCD risk reduction
EzetimibeWorks by blocking the body's ability to absorb cholesterol in the gutBy mouth, usually once dailyDiarrhea, stomach pain, muscle or joint pain, runny or stuffy nose, feeling tiredIn some patients, adding ezetimibe to statin therapy lowered cardiovascular events.
Bempedoic acidPartly blocks the production of cholesterol in the liverBy mouth, once dailyMuscle 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 swellingLowers cardiovascular risk in patients at risk for cardiovascular disease events who cannot take statin therapy.
PCSK9 inhibitorsWorks 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 wayStops PCSK9 from being produced in the liver.Given under the skin 2 times a year – every 6 months after two initial dosesPain, 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.

By adding a non-statin therapy, the goal is often to lower LDL cholesterol even more, lowering your chance of a future heart problem or stroke.

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.

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 Prevention

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

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