PCSK9 Inhibitors vs. Statins for High Cholesterol: 7 Ways They Compare

High cholesterol is a major risk factor for heart disease and stroke. If lifestyle changes alone aren’t enough to bring your cholesterol down, your healthcare team may recommend a medication.

You’ve likely heard of statins, such as atorvastatin (Lipitor, Atorvaliq) and simvastatin (Zocor, FloLipid). But there’s also a newer class of injectable cholesterol medications called PCSK9 inhibitors available. Both lower LDL, or “bad,” cholesterol and reduce the risk of serious cardiovascular events. But they work differently and have different forms, costs, and side effects.

Comparing PCSK9 inhibitors and statins

Here’s a quick comparison of PCSK9 inhibitors and statins to help highlight how they differ in terms of use, cost, availability, and more. While both are used to lower cholesterol, they work in different ways and may be recommended in different situations.

Next, we’ll dig deeper into seven ways PCSK9 inhibitors and statins compare.

1. PCSK9 inhibitors and statins work differently to lower cholesterol

Both PCSK9 inhibitors and statins lower LDL cholesterol, but they work in different ways. Statins primarily reduce cholesterol production in the liver. PCSK9 inhibitors, on the other hand, mostly help remove LDL cholesterol from the blood.

Statins are chemical-based (small molecule) medications. They work by blocking an enzyme (protein) in the liver called HMG-CoA reductase, which the body needs to make cholesterol. This slows down cholesterol production in the liver. As a result, the liver also removes more LDL cholesterol from the bloodstream, further lowering LDL levels.

Unlike statins, PCSK9 inhibitors are monoclonal antibodies — a type of biologic medication made from living sources. They block a protein called PCSK9, which normally causes the breakdown of LDL receptors (binding sites) in the liver. These receptors are responsible for clearing LDL cholesterol from the blood. By blocking PCSK9, more receptors stay active, allowing the liver to remove more LDL cholesterol from the bloodstream.

Statins and PCSK9 inhibitors are effective at lowering cholesterol on their own. But some people may not be able to reach their LDL target with just one medication. In this case, PCSK9 inhibitors can be used with statins for additive effects.

2. Statins are taken by mouth, while PCSK9 inhibitors are injected

Another key difference between statins and PCSK9 inhibitors is how you take them. Statins are oral medications that you take every day. PCSK9 inhibitors are injected under the skin (subcutaneously) once or twice a month.

There are many statins available, all of which come in pill form. But atorvastatin and simvastatin also come in liquid forms (Atorvaliq, FloLipid) if you have trouble swallowing pills. Some statins should be taken at night, while others can be taken at any time of day.

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Repatha and Praluent are the only PCSK9 inhibitors on the market. You can administer them at home after your healthcare team shows you how. Both come in single-dose prefilled pens. But Repatha is also available in a prefilled syringe and a hands-free device that infuses the medication into your body.

3. PCSK9 inhibitors and statins have similar but slightly different approved uses

Both PCSK9 inhibitors and statins are approved to lower LDL cholesterol and reduce the risk of serious cardiovascular problems in certain people. They’re also used to treat certain types of inherited causes of high cholesterol. But statins have broader uses across different types of high cholesterol. Here’s how they compare.

Your prescriber will consider your health history, risk factors, and goals when deciding if a statin, PCSK9 inhibitor, or both is best for you.

4. PCSK9 inhibitors and statins are both effective, but statins are considered a first-choice treatment

Both PCSK9 inhibitors and statins are effective at lowering LDL cholesterol. But statins are considered first-choice treatments. PCSK9 inhibitors are generally reserved for people who are unable to reach their LDL goal with statins or other cholesterol-lowering medications.

How much a statin lowers LDL cholesterol is referred to as its intensity — ranging from low to high. High-intensity statins, such as atorvastatin and rosuvastatin, can lower LDL cholesterol by 50% or more. They can also lower triglycerides and raise HDL, or “good,” cholesterol.

PCSK9 inhibitors lower LDL cholesterol by 45% to 65% and modestly affect triglycerides and HDL levels. They also appear to have similar benefits as statins in reducing serious cardiovascular problems in certain people. But only statins have been shown to reduce cardiovascular-related deaths, which is a key differentiator.

In most cases, your prescriber will have you try a statin first. A PCKS9 inhibitor may be added if you need additional LDL lowering or if you aren’t able to tolerate your statin.

5. PCSK9 inhibitors and statins can cause different side effects

PCSK9 inhibitors and statins affect the body differently, so they can cause different side effects. For example, statins are associated with muscle-related side effects, which may not be as common with PCSK9 inhibitors. And since they’re injected, PCSK9 inhibitors can cause side effects such as redness, swelling, and pain at the injection site.

Potential side effects can vary across PCSK9 inhibitors and statins, but we’ve detailed a general list of reported side effects in the table below.

If you’re not able to tolerate statins because of side effects, your prescriber may consider having you try a PCSK9 inhibitor.

6. PCSK9 inhibitors and statins have different interactions

PCSK9 inhibitors have few known drug interactions. Statins, on the other hand, are more likely to interact with other medications and substances. That’s because some statins are processed through the liver. In these cases, certain medications, foods, and supplements can affect how they’re broken down.

Examples of substances that can interact with statins include:

• Fibrates, such as gemfibrozil (Lopid)

• Transplant rejection medications, such as cyclosporine (Sandimmune), tacrolimus (Prograf), and sirolimus (Rapamune)

• Colchicine (Colcrys, Lodoco)

• Paxlovid (nirmatrelvir / ritonavir)

• Alcohol

• Grapefruit juice

Make sure your healthcare team has your complete medication list to help them check for interactions. Some interactions can be managed with dosage changes, while others should be avoided altogether.

Good to know: Statins and PCSK9 inhibitors are generally safe to take together. There are no known clinically significant interactions between them. And studies suggest that PCSK9 inhibitors don’t increase the risk of statin-related muscle symptoms.

7. Statins are available as generics, but PCSK9 inhibitors are brand-name only

PCSK9 inhibitors are currently only available as brand-name medications. Most statins are available as lower-cost generics, which makes them a more affordable option for many people.

The best way to save on PCSK9 inhibitors is to use your insurance. How much you’ll pay depends on your plan. And a prior authorization may be required before the medication is covered. If your copay is still high, the manufacturers of Praluent and Repatha offer copay cards to help lower the cost. And if you’re uninsured, patient assistance programs are also available.

Generic statins are often covered by insurance. But if your copay is high, or if you don’t have insurance, many statins are available for less than $50 by using GoodRx at certain pharmacies.

GoodRx offers savings on several brand-name products, too, though. For instance, anyone with a valid prescription, regardless of insurance status, can use GoodRx to purchase two Repatha autoinjectors or syringes at an exclusive cash price of $239.

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Written by:

Alyssa Billingsley, PharmD

Alyssa Billingsley, PharmD, is the director of pharmacy content for GoodRx. She has over a decade of experience as a pharmacist and has worked in clinical, academic, and administrative roles.

Reviewed by:

Christina Aungst, PharmD

Christina Aungst, PharmD, is a pharmacy editor for GoodRx. She began writing for GoodRx Health in 2019, transitioning from freelance writer to editor in 2021.

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