By Stephen L. Kopecky, MD, as told to Susan Bernstein
Stephen L. Kopecky, MD, is a professor of medicine and a consultant for the Division of Preventive Cardiology, Department of Cardiovascular Medicine, at the Mayo Clinic in Rochester, MN. He is the author of Live Younger Longer: 6 Steps to Prevent Heart Disease, Cancer, Alzheimer's, and More, publishing in August 2021.
We want patients with high cholesterol to know three things. One, high cholesterol is really a culprit in heart disease. If the cells in your body don’t get cholesterol, it’s harmful. But too much can be worse. The second thing to know is that there is cholesterol in the plaque that’s inside your arteries, and we have medications that are treatments for this. The third thing to know is that these treatments are safe and effective. If there are side effects, we can deal with them.
The New Landscape of Cholesterol Medications
While statins are the mainstays of treatment, one of the most helpful of the newer medications is ezetimibe (Zetia). It’s a generic now, so it’s less expensive than it used to be. It’s especially helpful in people who are 75 or older.
PCSK9 drugs, which are monoclonal antibodies, are another game-changer in cholesterol management. These drugs block the PCSK9 protein. As low-density lipoprotein (LDL) cholesterol -- what people call “bad” cholesterol -- goes into your liver, the PCSK9 will hold the LDL and the LDL receptor together.
What usually happens is the LDL fits into the LDL receptor on the surface of the liver cell. When the LDL fits into the LDL receptor on the liver, the PCSK9 protein will hold the receptor and the LDL together so the liver metabolizes them both. The receptor can’t be used again.
With these drugs, both the receptor and the LDL go into the cell. The liver metabolizes the LDL, but the receptor is freed up to be used again to process more LDL. Usually, the receptor can be reused around 200 times total. This markedly reduces your LDL cholesterol levels.
PCSK9 inhibitors have the same side effect profile as statins, including myalgias (muscle pains) and nasal stuffiness, although this usually goes away. These drugs have also started to come down in price, and more insurance companies are accepting them. This treatment is very helpful for patients with familial hypercholesterolemia (FH) who may not be able to get to their cholesterol goals with a combination of a statin and ezetimibe alone. The PCSK9 drug works on top of the statin and ezetimibe for these patients.
Long-Acting Treatment
Inclisiran is as close as we have to a vaccine for high cholesterol in the near future. It works on your RNA -- one of the nucleic acids that carries your genetic code. It helps your body do what it’s supposed to do. This may be especially helpful for FH patients, who have high cholesterol because of genetics. My patients with FH often say to me, “Why do I always feel like I’m being blamed for my high cholesterol?” We need to do a better job of making sure that people don’t feel that way.
Inclisiran (Leqvio) is currently in phase III studies. It can lower cholesterol, but it remains to be seen if it lowers the incidence of cardiovascular events such as heart attacks. We have had other medications that lower your numbers or raise HDL (“good”) cholesterol but didn’t lower cardiovascular events. This is a small, RNA-interfering drug -- it makes it so the body can’t use the RNA, so you make less PCSK9.
You can take inclisiran only once every 6 months, which may appeal to some patients. But I have some FH patients in my clinic who say, “I’ll have this drug in my system for 6 months? Will I have side effects for 6 months?” We encourage people to ask such questions about their medications.
Other New Treatments
Another new treatment that may come out soon is one that blocks lipoprotein-a. It’s in studies now. You would take these drugs as one shot under the skin every 6 months. Lipoprotein-a is part of the LDL family, but it’s also pro-inflammatory and promotes clotting. This combination can be devastating. This si-RNA drug would block that process from happening -- it’s very targeted.
PCSK9 drugs were game-changers. For the first time in the history of our species, people with familial hypercholesterolemia have a treatment option. Lipoprotein-a drugs will be a game-changer too.
There are some other newer treatments, including bempedoic acid, which is an adenosine triphosphate-citrate lyase (ACL) inhibitor. It’s like a statin but works earlier in the cholesterol formation pathway than statins. It doesn’t have the same myalgia side effects as statins, but it may raise uric acid levels and make gout worse in people who have that condition. It may also have a link to an increased risk of tendon rupture.
Bempedoic acid is appropriate for many patients on the maximum dose of statins and those with genetic causes of high LDL. But we have to be careful, talk about the side effects, and watch them carefully, especially if they have a history of tendon rupture.
There is another exciting newer treatment, a fish oil called Vascepa. This is purified EPA, unlike classic fish oil. It’s a fish oil, but it’s prescription only. It seems to lower your risk of heart attacks and strokes if you’re on a statin for your LDL, but your triglyceride levels are high.
Lifestyle Changes Are Still the Key
Even with these treatment advances, never forget about your lifestyle if you have high cholesterol. It’s important that patients do all they can through their lifestyle to try to modify their cholesterol levels. If you already have heart disease, or if you have had a heart attack or have a stent, there’s no time to wait. You do need to start taking medications early.
Dietary changes can help, especially eating foods that help lower cholesterol or avoiding processed foods and processed meats. About 58% of the calories we eat in the U.S. are classified as ultra-processed foods. If you don’t eat healthfully -- including more fruits and vegetables, less red meat, and less processed food -- your cholesterol numbers may look better, but your risk of a heart attack or your eventual need for a stent doesn’t go down to an equal degree.
It’s all about having good lifestyle habits. The advances we’re making are great, and the si-RNA molecules in particular will be very helpful for some people. But a pill doesn’t replace a healthy lifestyle.
