Beyond Daily Pills: Exercise, Treatment Adherence and a One-Time PCSK9 Treatment

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• Exercise and cholesterol levels
• What happened when runners stopped running
• The problem of staying on treatment
• A one-time treatment aimed at PCSK9
• How long the effect may last
• Full Transcript

Exercise and cholesterol levels

Exercise has a limited effect on cholesterol levels, cardiologist Dr. Paul D. Thompson, MD, tells Dr. Anton Titov, MD. Exercise does raise the good cholesterol level and lower the triglyceride level, he says, but its effect on LDL, which he calls the ugly cholesterol, is pretty low. Endurance athletes have an LDL level about eight to 10% lower than their sedentary counterparts. Still, Dr. Thompson calls exercise a very important part of heart disease prevention and of keeping muscles strong with age.

What happened when runners stopped running

A study in which his group paid distance runners to stop running supports his view that much of that LDL difference is dilutional, because exercise expands the fluid in the bloodstream. Within two days of stopping exercise, the runners' plasma volume went down about 6% and their LDL cholesterol went up about 8%. He thinks the effect of exercise on lipid levels is very weak.

The problem of staying on treatment

Staying on cholesterol-lowering medication is a problem, in Dr. Thompson's view. Only about 50% of people started on statins are still taking them a year later. For the injectable PCSK9 inhibitors, which block the compound that binds the LDL receptor and destroys it in the liver, the figure is only about 20 to 25% at one year. He calls this a big unmet need in medicine and cardiology.

A one-time treatment aimed at PCSK9

A one-time treatment in development is the advance Dr. Thompson highlights. A company is developing an infused compound designed to attach to liver cells, where cholesterol is made. Inside the liver cell it acts on the DNA so that the cell can no longer produce PCSK9. With nothing left to grab the LDL receptors, the receptors stay alive longer and the cholesterol level stays lower longer.

How long the effect may last

Dr. Thompson says that in studies so far it has lasted at least a year, and he thinks it will last a lifetime, because liver cells divide and pass the change on to the new liver cells. He thinks it is a one-and-done injection.

Full Transcript

Dr. Anton Titov, MD: Future of cholesterol treatment, the next decade for preventing heart disease. Treatment of high cholesterol spans statins, ezetimibe, bempedoic acid and injectable medications. Exercise, too, treats and prevents heart disease. Professor Thompson, what advances can we expect in cholesterol treatment over the next decade? How could exercise and medication work together?

Dr. Paul D. Thompson, MD: So we do not think exercise has a lot to do with cholesterol levels. Now, exercise does raise the good cholesterol level. Exercise does lower the triglyceride level, but the effect on LDL, the effect on the ugly cholesterol level from exercise, is pretty low.

Dr. Paul D. Thompson, MD: In fact, we think a lot of that is just dilutional. Endurance athletes have an LDL, an ugly cholesterol level, about eight to 10% lower than their sedentary counterparts. We did a study in which we paid distance runners to stop running, and here is what happened.

Dr. Paul D. Thompson, MD: When they stopped running, their plasma volume went down because exercise expands the amount of fluid in your bloodstream, and their LDL cholesterol went up. In fact, their LDL went up about 8%, and their plasma volume went down about 6% within two days of stopping exercise. So we think a lot of the reduction in LDL with exercise is due to just fluid expansion.

Dr. Paul D. Thompson, MD: Now, exercise is a very important part of a heart disease prevention strategy, and also important to keep your muscles strong as you get older. We think the effect of exercise on lipid levels is very weak. You mentioned the great drugs we have on hand to treat cholesterol levels.

Dr. Paul D. Thompson, MD: The problem with those drugs is that people do not stay on them. Only about 50% of people started on statins are on them in a year. We talked about those injectable PCSK9 inhibitors that inhibit that compound that binds the LDL receptor and destroys it in the liver.

Dr. Paul D. Thompson, MD: Only about 20 to 25% of people started on those injectable drugs are still on them one year later. So there is a big unmet need in medicine and cardiology: how do you keep people's cholesterol levels low if they do not keep on the drug? There is a company developing a compound that you infuse.

Dr. Paul D. Thompson, MD: The compound is designed to go and attach to the liver cells, and in the liver it releases a compound that blocks the production of that PCSK9 molecule that binds to the LDL receptor. We think this is a one-and-done injection because that molecule goes to the liver cells. Remember, cholesterol is made in the liver.

Dr. Paul D. Thompson, MD: That molecule goes to the liver cells. It gets into the liver cell. It affects the DNA within the liver cell so that the DNA in that liver cell can no longer produce PCSK9.

Dr. Paul D. Thompson, MD: There are no grabbers to grab the LDL cholesterol receptor. The LDL receptors stay alive longer. The cholesterol level stays lower longer.

Dr. Paul D. Thompson, MD: Now, this drug has been studied. Its duration has lasted at least a year. We think it is a lifetime duration.

Dr. Paul D. Thompson, MD: Why is that? Because liver cells divide and produce new liver cells, and they will pass on that genetic alteration as they make new liver cells.