Low-density lipoproteins (LDL) are sometimes known as “bad” cholesterol. LDL receptors are the most important tool your body uses to help regulate LDL cholesterol in your blood.

Every person also has a gene called proprotein convertase subtilisin/kexin type 9 (PCSK9) that directly affects the number of LDL receptors in the body. Some mutations of this gene can lower LDL receptors and increase your risk of conditions like heart disease, heart attacks, or stroke.

PCSK9 inhibitors can help treat high cholesterol by directly modifying this gene to reduce the amount of LDL in your body.

Learn about the PCSK9 gene, how PCSK9 inhibitors affect LDL cholesterol levels, and whether this medication is right for you if you’re concerned about LDL cholesterol.

PCSK9 inhibitors suppress the PCSK9 enzyme expressed by the gene. Here are common PCSK9 inhibitors and what the research says about their effectiveness.

Evolocumab (Repatha)

One common PCSK9 inhibitor called evolocumab (Repatha) was approved by the Food and Drug Administration (FDA) in 2015.

The substance evolocumab used in Repatha is known as a monoclonal antibody protein. In this case, that means the evolocumab protein attaches to and blocks the PCSK9 gene from reducing LDL receptors.

This action allows more receptors to lower LDL cholesterol in the blood without the interference of the PCSK9 gene.

A 2015 clinical trial found that people taking evolocumab for 1 year reduced their LDL cholesterol by about 60 percent compared to those who didn’t take it. In the following year, just under 1 percent of people taking evolocumab had a heart-related event as compared to over 2 percent of people who weren’t taking the medication.

Alirocumab (Praluent)

Alirocumab (Praluent) is another commonly used PCSK9 inhibitor that was approved by the FDA in July 2015.

Just like evolocumab in Repatha, the substance alirocumab used in Praluent is a monoclonal antibody protein that attaches to the PCSK9 gene. This blocks the gene from reducing LDL receptors that help lower LDL cholesterol in the body.

A 2015 clinical trial also showed success in lowering LDL cholesterol — only 1.7 percent of people studied experienced some type of heart-related event during the trial’s 78-week period.

Side effects reported in clinical trials differed slightly between people using evolocumab and people using alirocumab. Long-term side effects and risks of these medications have not yet been fully explored in the research.

Side effects can include the following:

Evolocumab (Repatha)

Side effects were reported in 69 percent of people taking evolocumab in clinical trials, including:

  • swelling or rash at the injection site
  • limb pain
  • fatigue

Less than 1 percent of people in the evolocumab trial reported:

  • mental confusion
  • difficulty focusing
  • other neurocognitive issues

Alirocumab (Praluent)

In alirocumab trials, 81 percent of people taking the drug reported side effects, such as injection-site reactions and muscle pain.

Just over 1 percent of people taking Alirocumab reported neurocognitive adverse events, such as memory impairment and confusion.

Both PCSK9 inhibitors and statins are often used to help lower LDL cholesterol, especially when statins or lifestyle changes haven’t helped lower LDL cholesterol.

A 2017 review in the World Journal of Cardiology suggested that using PCSK9 inhibitors could help lower LDL cholesterol levels in the blood by 50 percent or more above that achieved by statins alone.

PCSK9 are delivered as injections that directly affect the activity of the PCSK9 gene. Statins taken as oral tablets or capsule can:

  • block HMG-CoA reductase, an enzyme that your liver uses to make cholesterol
  • help your body reabsorb built-up cholesterol deposits from your arteries

Affordable brand name and generic statins are available as prescriptions. PCSK9 inhibitors require injections every 2 to 4 weeks in a medical facility and may be more costly since there aren’t generic versions of these medications.

Most people can take statins, but side effects like digestive problems and muscle pain may make it difficult for some people to tolerate. PCSK9 inhibitors may provide another option for people with LDL cholesterol who are at high risk of heart disease but can’t tolerate statins.

Talk to a doctor about how statins work in the long term and how they may affect you. Research is still not conclusive as to how PCSK9 inhibitors will affect cardiovascular events over time.

PCSK9 inhibitors aren’t usually a first-line treatment for lowering LDL cholesterol. They’re often taken alongside other treatments like statins, or are used when other medications haven’t worked.

A doctor may prescribe a PCSK9 inhibitor if you’ve already been prescribed two different treatments to lower LDL cholesterol and your LDL cholesterol is still high. In many cases, this will likely include a statin or medications like bile acid resins.

You may also be prescribed a PCSK9 inhibitor if you have a condition called familial hypercholesterolemia. This is a genetic condition that can result in high cholesterol levels that require medication.

The U.S. Centers for Disease Control and Prevention (CDC) estimate that 93 million adults in the United States have high LDL cholesterol. Statins are currently used as a first-line treatment for people who have trouble controlling their cholesterol through lifestyle changes like diet and exercise.

PCSK9 inhibitors are an injectable treatment for high LDL cholesterol that may provide a safe alternative for people who can’t take statins or who have genetic conditions that increase the risk of high cholesterol. More research is needed to suggest how effective they are at lowering LDL cholesterol alone by directly disrupting the genetic processes that can reduce LDL receptors in the body.

Talk to a doctor about whether you’re a candidate for these medications and what to expect in the long-term.