Besides Statins, What Other Medicines Lower Cholesterol?

Non-statin cholesterol medications include ezetimibe, bile acid sequestrants, PCSK9 inhibitors, bempedoic acid, fibrates, niacin and prescription omega-3 products. Each works differently and lowers different lipids, so the choice depends on your numbers, your heart risk, and what you tolerate. This article compares them, explains what each is usually used for, and lists the symptoms that need urgent care. Your clinician decides which fits you.

Which cholesterol medicines are used besides statins?

Statins are often the first medicine prescribed for high LDL ("bad") cholesterol. If you want the full picture on that group, see our article on atorvastatin and statins. This page covers the other options. According to MedlinePlus, several types of cholesterol medicines exist, and statins are only one of them (Cholesterol Medicines).

A clinician may add or choose a non-statin medicine for several reasons:

• LDL cholesterol stays above the target your clinician sets for your risk category despite the highest statin dose you tolerate.
• Side effects, such as muscle symptoms, make a statin hard to take.
• Triglycerides are very high, which statins affect less.
• An inherited condition causes very high LDL.
• Another medicine you take may interact with a statin.

Lifestyle changes still matter alongside any drug. MedlinePlus describes how to lower cholesterol, including how to lower cholesterol with diet, through eating patterns, activity and weight, and these can work together with medicine.

Ezetimibe (Zetia)

Ezetimibe works in the small intestine. It reduces how much cholesterol from food and bile is absorbed into the blood. It is taken as a once-daily pill and is often prescribed together with a statin when LDL remains above goal, or by itself when a statin is not tolerated.

Side effects can include diarrhea, stomach upset, and muscle or joint aches. Tell your clinician about liver disease. The ezetimibe product label advises liver tests when it is used with a statin, and advises against that combination in active liver disease or unexplained persistent elevations of liver enzymes. Ask the prescriber or pharmacist about your own situation and read the product label.

Bile acid sequestrants

This group includes cholestyramine, colestipol and colesevelam. They bind bile acids in the gut so the body removes them in stool. The liver then pulls more cholesterol from the blood to make new bile acids, which can lower LDL.

• Common side effects: constipation, bloating, gas and nausea.
• Interactions: they can reduce absorption of other medicines. Labels generally advise taking other medicines at set intervals before or after the sequestrant, and the interval differs by product; ask your pharmacist for the exact schedule for your own medicines.
• Triglycerides: some of these products may raise triglycerides, so clinicians use caution when levels are already high.

PCSK9 inhibitors: injections for high-risk LDL

Alirocumab (Praluent) and evolocumab (Repatha) are antibody medicines given by injection under the skin on a schedule your care team teaches you. They block a protein called PCSK9. PCSK9 normally causes LDL receptors on liver cells to be broken down; blocking it leaves more receptors to remove LDL from the blood. Your prescriber decides whether you keep taking your statin when a PCSK9 inhibitor is added; do not stop or change it on your own.

A published systematic review of lipid-lowering guidelines for secondary prevention (Systematic review of clinical guidelines for lipid lowering in the secondary prevention of cardiovascular disease events) found that recommendations generally focus on people with established heart or blood vessel disease. The product labels for alirocumab and evolocumab describe use mainly in people with established cardiovascular disease or inherited high LDL whose LDL stays high despite other treatment, such as the highest statin dose they tolerate with ezetimibe. Ask your prescriber how this applies to you. Common effects include injection-site reactions. Cost and insurance approval can be a barrier, so your care team may need to submit prior authorization.

Inclisiran (Leqvio) is a small interfering RNA medicine that reduces PCSK9 production in the liver. A clinician gives it by injection at scheduled visits, on a schedule set in its product label rather than at home. Common effects include injection-site reactions, and your prescriber can explain how it compares with the antibody injections.

Bempedoic acid (Nexletol) and the combination with ezetimibe

Bempedoic acid blocks an enzyme earlier in the same cholesterol pathway as statins. It is activated mainly in the liver rather than in muscle, which is thought to explain why it may be considered for people with statin muscle symptoms, though it can still cause muscle effects. It is also available combined with ezetimibe (Nexlizet).

The product label includes warnings about tendon problems, including tendon rupture, and about raised uric acid levels that can lead to gout. Tell your prescriber if you have gout or kidney disease, since bempedoic acid can raise uric acid, and if you have had tendon problems, are over 60, or take a corticosteroid or fluoroquinolone antibiotic, since these can raise tendon risk. Sudden pain, swelling or a snapping sensation in a tendon, such as the back of the ankle, needs same-day medical evaluation. The Nexletol label advises that the medicine be discontinued at the first sign of tendon pain, swelling or rupture, so contact your prescriber the same day to decide what to do, and rest the area until you are seen. If you cannot walk or bear weight, go to the emergency room.

Fibrates, niacin and omega-3 products: mainly for triglycerides

These medicines are used more for high triglycerides than for LDL, although they can affect several lipids. Very high triglycerides can contribute to pancreatitis, which is one reason clinicians treat them.

• Fibrates (fenofibrate, gemfibrozil): lower triglycerides and may modestly raise HDL. The gemfibrozil label warns that taking it with a statin raises the risk of muscle injury, including a serious breakdown of muscle (rhabdomyolysis), and the combination is generally avoided. Fenofibrate is often considered instead when a fibrate is needed with a statin. Any such combination needs prescriber supervision. Gallstones and liver enzyme changes are among the label cautions, so severe upper abdominal pain that spreads to the back or shoulder, especially with vomiting, needs emergency care.
• Prescription niacin: can lower LDL and triglycerides and raise HDL. Flushing, itching and stomach upset are common. Higher doses can affect the liver, raise blood sugar and bring on gout. In two large trials of people already taking statins (AIM-HIGH and HPS2-THRIVE), adding niacin did not reduce cardiovascular events, and HPS2-THRIVE reported more side effects, so clinicians weigh the harms carefully. Do not substitute over-the-counter niacin supplements for a prescribed product, since the products are not interchangeable. Prescription niacin carries cautions for people with liver disease, gout, diabetes or active stomach ulcers, so your prescriber should review these with you.
• Prescription omega-3 fatty acids (icosapent ethyl, omega-3-acid ethyl esters): omega-3-acid ethyl esters are used for severely high triglycerides. According to the Vascepa product label, icosapent ethyl is indicated both for severe hypertriglyceridemia and, as an add-on to a statin in adults with elevated triglycerides and established cardiovascular disease, or diabetes with other risk factors, to reduce cardiovascular events. They differ from over-the-counter fish oil capsules, which are sold as supplements. The labels warn that atrial fibrillation or flutter (palpitations or an irregular heartbeat) and bleeding have been reported, particularly in people who also take anticoagulants or antiplatelet medicines, so tell your clinician if you take a blood thinner or have a heart rhythm problem. The labels also advise caution if you have a fish or shellfish allergy, so mention it to your prescriber or pharmacist. Fainting, chest pain or severe breathlessness with a racing or irregular heartbeat needs emergency care: call 911. Bleeding that will not stop or vomiting blood also needs a 911 call, especially if you take a blood thinner. Black, tarry stools need emergency room evaluation the same day, and 911 if you also feel faint or dizzy.

How the options compare

The table below summarizes how each non-statin cholesterol medication works, what it mainly targets and how it is taken.

This table is a general overview. Individual benefit and risk depend on your health history, and outcomes vary.

Why a clinician may choose a non-statin first

Muscle aches are the most frequently reported reason people stop statins, but they can have several causes, and the mechanism is not fully understood. A clinician may check for other contributors, such as thyroid problems, other medicines, or heavy exercise, before deciding that a statin is the problem. Some people try a different statin or a lower dose first. If a statin is truly not tolerated, ezetimibe, bempedoic acid or a PCSK9 inhibitor may be considered. Do not stop a prescribed statin on your own; talk with the prescriber first. Statin safety is also discussed in MedlinePlus: Statins.

Safety points that apply to most cholesterol medicines

• Pregnancy and breastfeeding: tell your clinician if you are pregnant, planning pregnancy or nursing, since some of these medicines are handled differently in these situations.
• Grapefruit and other interactions: some lipid medicines interact with foods and drugs. Our article on grapefruit and drug interactions explains the general idea, and your pharmacist can check your list.
• Supplements: red yeast rice and other products sold as cholesterol aids are not regulated like prescription drugs, and some contain a statin-like compound. Mention them to your clinician.
• Blood tests: your clinician may order a lipid panel and liver tests to see how a medicine is working and whether it is suitable. Keep up with monitoring your doctor recommends.
• Aspirin: a daily aspirin is a separate decision from cholesterol treatment. See our article on daily aspirin for heart attack prevention.

Questions to bring to your appointment

• What is my LDL, and what target fits my heart risk category? Clinicians generally set LDL targets by risk group when deciding whether to add a non-statin.
• Are muscle symptoms or other side effects related to my statin?
• Would an added medicine or a switch be appropriate for me?
• How will we monitor safety and effect?
• What will it cost, and does my insurance need prior authorization?

To understand your numbers first, see our pieces on the cholesterol ratio, high LDL with normal total cholesterol, and low HDL results.

When to Seek Medical Care