PCSK9: What You Need to Know

You may have heard about PCSK9 inhibitors, and how this class of drugs could be the next great breakthrough in the treatment of high cholesterol. To understand how this new medication class works, you have to first understand the PCSK9 gene.

Read on to learn about this gene, how it affects blood cholesterol levels, and how researchers are using that information to create new treatments for an all-too-common problem.

We all have a gene called proprotein convertase subtilisin/kexin type 9 (PCSK9). This gene directly affects the number of low-density lipoprotein (LDL) receptors in the body. LDL receptors help regulate the amount of LDL cholesterol that enters the bloodstream. Most LDL receptors are found on the surface of the liver.

Certain mutations of the PCSK9 gene can lower the number of LDL receptors. This can cause an inherited form of high cholesterol, known as hypercholesterolemia. High LDL cholesterol may lead to cardiovascular disease, heart attack, or stroke.

Other mutations of the PCSK9 gene can actually lower LDL cholesterol by increasing the number of LDL receptors. People with lower LDL cholesterol levels have a lower risk of developing heart disease and stroke.

PCSK9 drugs suppress the PCSK9 enzyme expressed by the gene. That’s why they’re called PCSK9 inhibitors.

In August 2015, the Food and Drug Administration (FDA) approved evolocumab (Repatha), a PCSK9 inhibitor from Amgen. In clinical trials, people taking evolocumab for one year reduced their LDL cholesterol by about 60 percent when compared with the control group. One year later, slightly over 2 percent of those in the standard therapy group had a major heart-related event compared to just under 1 percent of those taking evolocumab.

In July 2015, the FDA approved alirocumab (Praluent). A recent clinical trial had similar success in lowering LDL cholesterol. Only 1.7 percent of patients experienced some type of heart-related event during the 78-week trial.

All medications have the potential for side effects. Adverse events were reported in 69 percent of people taking evolocumab in the clinical trials. Injection-site swelling or rash, limb pain, and fatigue were some of the reported side effects. Less than 1 percent reported mental confusion, difficulty focusing, or other neurocognitive issues.

In the alirocumab trials, adverse events were reported in 81 percent of participants taking the drug. These included injection-site reactions, muscle pain, and eye-related events. Slightly more than 1 percent of participants reported neurocognitive adverse events. These included memory impairment and confusion.

Long-term side effects and risks are not yet known.

Both PCSK9 inhibitors and statins have been shown to be effective in lowering LDL cholesterol.

Statins work by blocking HMG-CoA reductase. That’s an enzyme your liver uses to make cholesterol. Statins also help your body reabsorb built-up cholesterol deposits from your arteries. Most people can take statins without difficulty, but some people can’t tolerate side effects like digestive problems and muscle pain. Statins have been around for a long time, so your doctor can give you information about how they work in the long term. They’re available in brand name and generic tablets and have become quite affordable.

PCSK9 inhibitors may provide another treatment option for people who have high LDL cholesterol, are at high risk of cardiovascular disease, and can’t tolerate statins. These newer drugs require injections every two to four weeks. We don’t yet have enough information to know how PCSK9 inhibitors will reduce cardiovascular events over time.

According to the U.S. Centers for Disease Control and Prevention, 73.5 million adults in the United States have high LDL cholesterol. Statins are currently the first-line therapy for those who can’t control their cholesterol through diet and exercise.

PCSK9 inhibitors may become a viable alternative treatment for people who can’t take statins.

Keep reading: Cholesterol Control: PCSK9 Inhibitors vs. Statins