Cholesterol is a type of waxy fat that circulates in your blood. You need some cholesterol to make hormones and help you digest foods. But when you have too much, it builds up in your arteries. The excess cholesterol forms sticky deposits called plaques that can narrow blood vessels and reduce blood flow to your body.
Medicines like statins and PCSK9 inhibitors, plus healthy lifestyle changes, help to lower high cholesterol.
What Are the Treatments for High Cholesterol?
Lifestyle changes and medicines reduce the amount of cholesterol circulating in your blood. The goal of these therapies is to bring your low-density lipoprotein (LDL) cholesterol levels into a healthy range. This lowers your risk of heart disease, heart attacks, and strokes.
First-line treatments for high cholesterol
Statins are often the first treatment doctors prescribe.
Second-line treatments
Understanding how each of these medicines work, how you take them, and what side effects they might cause can help you have a more informed discussion with your doctor. Most people with high cholesterol take a statin first. If you don't see enough improvement on a statin or you can't tolerate the side effects, your doctor might switch you to a PCSK9 inhibitor.
Key Concepts for High Cholesterol Treatment
Types of cholesterol
Lipoproteins are proteins that carry cholesterol through your bloodstream. There are two types of lipoproteins. Low-density lipoprotein (LDL), or "bad" cholesterol, is the kind that collects in arteries and increases your risk of heart disease and strokes. High-density lipoprotein (HDL), or "good" cholesterol, pulls excess cholesterol out of your arteries and carries it to your liver to be removed from your body.
First-line vs. second-line treatment
A first-line treatment is the one your doctor prescribes first because it's the most effective medicine. Statins are the first-line treatment for high cholesterol. If statins don't lower your cholesterol levels enough or they cause side effects that you can't tolerate, your doctor will switch you to or add a second-line therapy like a PCSK9 inhibitor.
Genetic vs. lifestyle causes of high cholesterol
The two causes of high LDL cholesterol are lifestyle and genes. Lifestyle factors are the most common cause. A diet high in saturated and trans fats, a lack of exercise, smoking, and alcohol use can all contribute to high cholesterol. Some people inherit a genetic condition that raises their chances of very high cholesterol and heart disease. Familial hypercholesterolemia is a genetic disease that makes it harder for the body to remove LDL cholesterol.
Target cholesterol levels
When it comes to cholesterol levels, the lower the better. Your cholesterol goal might be slightly higher or lower than the standard target levels based on your age, health, and heart disease risk factors.
PCSK9 protein
PCSK9 stands for proprotein convertase subtilisin/kexin type 9. It's a protein that your liver makes to control the amount of cholesterol in your bloodstream. PCSK9 inhibitors block this protein to help your body remove more LDL cholesterol.
What Are Statins?
Statins are the first choice of treatment when lifestyle changes aren't enough to lower cholesterol. These medicines block an enzyme your liver needs to make cholesterol. Statins lower LDL cholesterol and another type of fat called triglycerides, and they increase HDL cholesterol.
How effective are statins?
These medicines can lower LDL cholesterol by 50% or more. Taking a statin may reduce your risk of diseases of your heart and blood vessels (cardiovascular disease), strokes, or heart attacks.
Each type of statin is available in different dosages. Generally, the higher the dosage, the more a statin will lower your LDL cholesterol levels. But some statins can bring your LDL to a certain level at a lower dose. Statin therapy is classified as low, moderate, or high intensity, depending on how much a certain drug can lower LDL at a given dosage.
Your doctor will prescribe a statin based on your unique risk of cardiovascular disease. If your LDL cholesterol levels are high, but your heart is otherwise in good health, you may take a low- or moderate-intensity statin. If you have other risk factors for cardiovascular disease as well, you'll likely get high-intensity therapy.
How do you take statins?
Statins are available as tablets or capsules that you take by mouth, usually once a day. You should swallow each tablet or capsule whole. Check your medication instructions to know if you should take your statins with or without food. Your instructions will tell you the best time to take your medication. If you have any questions, talk with your doctor.
Are statins safe?
Statins are safe for most people. But some people who take statins do have side effects like these:
Muscle pain is often listed as a side effect of statin drugs. But studies show the real risk of having muscle pain is 5% or less, compared with taking a non-statin drug. Researchers think that believing that you'll have muscle pain on statins is the biggest predictor of this side effect.
Who should not take statins?
Statins can affect your liver, so before your doctor prescribes them, you may have to take a blood test to check your liver and kidney function. You'll need to repeat the test after three months of treatment and at the end of your first year.
How much do statins cost?
Generally, statins are very affordable. Name -brand statins may cost several hundred dollars per year, but generics can be less than $20 per month. They're usually covered by most insurance plans.
What Are PCSK9 Inhibitors?
PCSK9 inhibitors are medicines that lower LDL cholesterol by blocking a protein called PCSK9. This protein destroys special receptors in your liver that help your body remove LDL cholesterol.
When are PCSK9 inhibitors prescribed to treat high cholesterol?
These medications might be an option if you can't take statins, they don't lower your cholesterol enough, or you have an inherited condition that causes very high LDL levels, such as familial hypercholesterolemia (FH). People with FH make more PCSK9 than usual because of an inherited gene mutation. Having extra PCSK9 increases LDL cholesterol levels.
How effective are PCSK9 inhibitors?
By blocking the PCSK9 protein, these medicines leave more receptors available to clear away LDL cholesterol.
The three approved medicines in this class are Leqvio, Praluent, and Repatha. Praluent and Repatha are PCSK9 inhibitors. Leqvio is a PCSK9 small interfering ribonucleic acid (siRNA). It lowers PCSK9 production by acting on ribonucleic acid (RNA), the genetic material in cells that holds the instructions for making this protein. Praluent and Repatha can reduce the risk of a heart attack by 27%.
How do you take PCSK9 inhibitors?
All three PCSK9 inhibitors come as shots that you either give yourself or a doctor gives you. Praluent and Repatha are given once every two to four weeks. The first and second doses for Leqvio are given three months apart. After that, you get the medicine once every six months.
Are PCSK9 inhibitors safe?
Research finds that these medicines are safe and have a low risk of side effects.
What are the side effects of PCSK9 inhibitors?
Most side effects from these medications are mild.
Who should not take PCSK9 inhibitors?
Don't take these medicines if you've ever had an allergic reaction to any of their ingredients.
How much do PCSK9 inhibitors cost?
The price of PCSK9 inhibitors has come down since they were first introduced. But they can still be expensive, with a list price of several hundred dollars per month. Most insurance companies cover them, but the approval process can be complex.
Many drug companies that make PCSK9 inhibitors offer patient assistance programs (PAPs) to help reduce out-of-pocket costs. If you qualify, you may be able to get these medications at a reduced cost or sometimes, for free. You may also be able to get a copay card that can reduce what you pay. Some drug companies will also help answer questions you have about your insurance coverage or other ways to get financial help.
You can find information about financial assistance for GLP-1 receptor agonists at:
Clinical trials for PCSK9 inhibitors
Researchers are still actively studying the safety and effectiveness of PCSK9 inhibitor medications.
Using clinical trials, they may compare different drugs in this class to each other, or to ones in other classes. This helps them know which work better and why.
You can find studies across the country by visiting ClinicalTrials.gov to learn:
- Basic information about the trial and what it's designed to study
- Whether the study is still taking applications
- Where it's located
- How to qualify
If you're interested in taking part in a clinical trial, your doctor may be able to recommend one that's a good fit for you.
5 Things to Consider When Choosing a PCSK9 Inhibitor for High Cholesterol
When deciding on a cholesterol medicine, talk to your doctor about your treatment goals and the benefits and risks of each drug. Here are five important things to ask about:
Condition. PCSK9 inhibitors are for people with familial hypercholesterolemia (FH), an inherited condition that causes very high LDL cholesterol. You may also take them if you have heart disease and are at increased risk of a heart attack, stroke, and angina. Doctors prescribe PCSK9 inhibitors to go along with diet changes and sometimes statins or other cholesterol-lowering drugs.
Statin response. Statins are the first-line treatment for high cholesterol that isn't well-managed with lifestyle changes alone. But PCSK9 inhibitors are an option if you're at high risk of heart disease and statins haven't lowered your cholesterol enough, or if you can't tolerate their side effects.
Dosing. All of the PCSK9 inhibitors come as shots. You get Praluent and Repatha once every two to four weeks. With Leqvio, you'll get the first two doses three months apart, and then a dose every six months.
Side effects. These medicines are generally safe, but side effects can happen. Common side effects include injection site reactions, muscle pain, and respiratory tract infections.
Cost and insurance coverage. PCSK9 inhibitors are expensive compared to statin drugs. They cost around $6,000 a year. Many insurance providers include these medicines in their drug lists, but coverage varies from plan to plan. Makers of these drugs offer financial assistance to help you afford your medication, both with and without health insurance.