Treatments That Help Lower Cholesterol

Treatments That Help Lower Cholesterol

Last month I discussed the role of lipids in atherosclerosis. This month, I’ll talk about treatment. For patients at high risk or those who have had a cardiovascular event (prior heart attack, stroke, stent, bypass, etc.), pharmacological treatment may be needed.

Cholesterol production and accumulation in the body involves three processes. First, intake from food in the intestine; second, production in the liver; and third, cholesterol removal from the arterial wall. All three of these can be targeted.

The dietary intake can be impacted by bile acid sequestrants (old treatments) or by Ezetimibe. This works by decreasing absorption.

The liver synthesis is the most important target at this time. This involves a long pathway using a substrate called Acetyl CoA, which ultimately is converted to cholesterol. The enzyme most important in this pathway is targeted by statins. These are very effective and are proven to reduce heart disease and stroke. There are many statins and physicians can use any of them depending on the patient. However, some patients cannot tolerate these.  For these patients, there are now a few options. First is a drug called bempedoic acid. This is a pro-drug, converted to an active form that blocks Acetyl CoA formation. Since it acts at a level before where statins act, side effects are not seen. This can be added to Ezetimibe to block both sources.

Finally, cholesterol removal. The LDL binds to receptors which help clearing. This process is prevented by PCSK9, produced by the liver. PCSK9 inhibitors are agents now available that are injectable and prevent this, causing clearance of LDL. This is highly effective and is injected every two weeks. This makes it easier to take rather than to be taking a pill every day.

Even more exciting is a new agent which works with RNA. This works on liver cells to increase the uptake of LDL into the cell. After the first injection, a repeat injection is given in 3 months. Subsequent injections are every 6 months.

 In summary, treat risk factors with diet and exercise. In high-risk patients and in patients with prior vascular or heart disease, high intensity statins are first choice to lower LDL by 50 percent. In patients who can’t achieve this and in those who cannot tolerate statins, other agents as described can be used. It is better to try and prevent rather than intervene after problems happen.

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