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Beyond Statins: 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 or atherosclerotic cardiovascular disease (ASCVD) risk enough. In other cases, someone might not be able to take a statin.

When this happens, several other medications—called non-statin therapies—offer additional treatment options. Often, a non-statin will be added to a statin.

Non-statin therapies:
- Are considered after you’ve gained the most benefit from a statin or
- In the rare case that you are unable to take 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 impairing 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 tiredSeems to carry a small additional reduction in cardiovascular events
PCSK9 inhibitorsWorks by helping the body clear 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, influenzaMore research is needed to understand how these drugs work over the long-term, but it seems these medications can reduce heart attacks or strokes and possibly related deaths among patients with heart disease or stroke
* These are just some of the potential 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 medications, including fibrates and omega-3 fatty acids (by prescription) may be recommended for overall dyslipidemia—an abnormal level of one or more kinds of lipid (fat) in your blood.

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.
  • Your health care team wants to lower your ASCVD risk more—helping to prevent a stroke or heart attack within a certain period of time.
  • 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 genetic disorder that results in very high levels of LDL cholesterol and cardiovascular disease at early ages.
  • 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.

TreatmentCan Lower LDL Cholesterol
Statins (high intensity)More than 50%
Ezetimibe Further lower by up to 25%
PCSK9 InhibitorsFurther lower by 60% among people taking a statin
Bile Acid Binding Resins (Sequestrants)15%-25%

PCSK9 inhibitors are the newest treatment and have been shown to significantly lower LDL. The effect is even greater when combined with a statin in the highest amount (dose) possible.


  • Last Edited 11/30/2018