People take statins to manage and reduce high cholesterol. However, powerful injectable alternatives for cholesterol management, known as PCSK9 inhibitors, have also become available in recent years.

Cholesterol is a waxy, fatty substance that circulates in the blood. If cholesterol builds up on artery walls, the walls can stiffen. This stiffening increases a person’s risk of cardiovascular disease (CVD). CVD is a common cause of death for both sexes, and high cholesterol is a leading risk factor for CVD development.

For some people, statins may not be an effective or suitable treatment option. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are newer alternatives to statins.

These drugs may be suitable for people with a high risk of cardiac events, such as heart attack and stroke, or severe genetic types of high cholesterol. PCSK9 inhibitors help the liver produce less cholesterol.

This article explains the current state of PCSK9 inhibitors, how they compare with statins, and where the field of injectable cholesterol-lowering drugs may head in the future.

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PCSK9 inhibitors are a type of monoclonal antibody or small interfering RNA (siRNA) that some people take as an alternative or complement to statins.

These medications can help lower cholesterol levels and reduce the risk of CVD, such as heart attack, stroke, and angina.

Monoclonal antibodies are medications that target specific proteins and switch them off by acting like cells in the immune system. These monoclonal antibodies block PCSK9, a protein in the liver that increases levels of low-density lipoprotein (LDL) — or “bad” cholesterol — in the blood. Small interfering RNAs achieve a similar effect by affecting PCSK9 production and lowering the level of LDL in circulation.

People can take PCSK9 inhibitors on their own or as a treatment alongside statins. They are extremely effective in reducing cholesterol. In a 2014 study, one PCSK9 inhibitor called evolocumab reduced LDL cholesterol by 53–56% among participants. A 2017 study on inclisiran, a different PCSK9 inhibitor, found a similar reduction in cholesterol (up to 52.6%) after two doses.

Statins come in the form of a daily pill. However, PCSK9 inhibitors require regular injections.

A 2019 meta-analysis found that PCSK9 inhibitors were more effective than statins at reducing cholesterol, achieved similar cardiovascular benefits, and did so with a lower risk of side effects than statins. Additionally, some people are resistant to the effects of statins or cannot take them.

Taking PCSK9 inhibitors as an add-on treatment to a course of statins may reduce cholesterol by 50–60% more than taking only statins, according to research from 2020. In a 2023 study, combination statin/PCSK9 therapy was also more effective than statins alone in reducing stroke risk by managing plaque on the walls of arteries.

There are three PCSK9 inhibitors with approval from the Food and Drug Administration (FDA):

  • Alirocumab (Praluent): In 2015, the FDA approved alirocumab as the first-ever PCSK9 inhibitor. It is a monoclonal antibody that is now approved to manage some genetic conditions that cause high cholesterol and reduce cholesterol in people with CVD who are already taking a maximum dosage of statins.
  • Evolocumab (Repatha): This monoclonal antibody has FDA approval as an add-on treatment to dietary changes or other therapies for people over the age of 10 years who have genetic forms of high cholesterol. The FDA also approved Repatha to reduce the risk of cardiac events in people with CVD.
  • Inclisiran (Leqvio): This siRNA had initial FDA approval in 2021 for people with heterozygous familial hypercholesterolemia and those with hardened arteries and CVD. In 2023, this drug also gained approval to include people with high LDL cholesterol and an increased risk of CVD.

Each type has a different dosage:

  • Praluent requires a 75-milligram (mg) injection once every 2 weeks or a 300-mg dose every 4 weeks.
  • Repatha requires a 140-mg injection every 2 weeks or a 420-mg dose every 4 weeks. For the 420-mg dose, a physician can infuse the whole dose over 5 minutes using an infuser or give three injections over the course of half an hour.
  • Leqvio requires a 284-mg dose each time, with healthcare professionals giving the first repeat dose after 3 months and then repeating every 6 months after that.

Doctors can adjust these to higher doses if cholesterol levels do not decrease enough.

Recent research on PCSK9 inhibitors is shedding more light on how people stick to courses of the drugs and their differing effects on males and females.

A 2023 study of 798 people taking PCSK9 inhibitors found that only 3.5% of those involved discontinued therapy. The study authors maintained that 95.2% of the participants showed “high adherence” to the therapy, meaning they stuck closely to their doctor’s instructions.

The drugs’ safety and effectiveness meant that people consistently stuck to their treatment plans.

A 2023 meta-analysis of six studies involving data from 1,857 people also found that PCSK9 inhibitors may reduce LDL cholesterol less for females than males.

A 2023 study assessing the efficacy and safety of inclisiran suggests that twice-yearly doses, in addition to statin therapy, can reduce LDL cholesterol levels beyond 6 years of treatment.

PCSK9 inhibitors cost more than $12,000 per year. Statins cost much less, with annual costs ranging from $313–1,428, depending on the type of statin and branding.

As many people who take PSCK9 inhibitors do so to manage genetic forms of high cholesterol that present in childhood, lifelong treatment with the drugs is likely. These costs add up over time. For example, 30 years of treatment with PSCK9 inhibitors could cost at least $360,000.

Most insurers only cover drugs to treat the conditions for which they have FDA approval. Many policies also exclude genetic conditions. This means that an individual may need to self-fund this treatment.

However, each of the PCSK9 inhibitors has a savings program available from the manufacturer. A person will need commercial insurance to be eligible for these programs. Below are links for the programs:

Clinical trials are currently assessing the safety and effectiveness of an oral PCSK9 inhibitor called MK-0616. This may reduce the need for regular injections in the future. A phase 2B trial suggests that reductions in LDL cholesterol could be as much as 60.9% from baseline, and people tolerated it well.

Future studies will also be able to shed light on the long-term risks and benefits of using these medications.

People with some causes of high cholesterol or an increased risk of cardiovascular events due to hardened arteries can take PSCK9 inhibitors an alternative or complement to statins. These drugs reduce cholesterol output by the liver.

Regular injections of Praluent, Repatha, and Leqvio have been effective at reducing LDL cholesterol in studies with a low risk of side effects. However, they are much more costly than statins.

People managing high cholesterol with medication can speak to a doctor about the best options for their underlying causes.