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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.

Your health care provider may have already talked with you about how a risk calculator can be used to determine your risk of developing ASCVD or having a heart attack or stroke. This calculator factors in things like:
  • Age
  • Gender
  • Race
  • Cholesterol
  • Systolic blood pressure (the top number)
  • If you smoke
  • If you have diabetes
Because your risk can change over time, it’s important to have ongoing conversations with your health care provider about what steps you can take to stay healthy.

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 tolerable amount (dose) of such statin 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.
  • Your preferences for treatment once you know/understand your risk

It is important to have your cholesterol levels retested. This is often done:

  • At the start of treatment
  • 6-8 weeks after starting a statin or new LDL cholesterol-lowering therapy
  • Periodically after that based on your doctor’s advice (sometimes within a few months, and sometimes just once a year)

As with starting any medication, talk with your health care provider, 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 expensive, newer drugs?
Key Points to Remember
  • 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
  • But statins by themselves may not produce a strong 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 lifestyle choices.

Always feel free to ask your health care team questions. When doing your own research, rely on sources of information that you can trust. For example:

Provides online education and tools for a wide array of heart-related conditions and tips for heart healthy living, brought to you by the American College of Cardiology.

Centers for Disease Control and Prevention


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

  • Last Edited 11/30/2018