New Cholesterol Guidelines (2026) - Part 3: Cholesterol-lowering medications that also lower cardiovascular risk

Year after year, new medications are produced that have an effect on lowering cholesterol. When I was a medical student 14 plus years ago, I recall these being the choices: statins, Zetia, fibrates, niacin, and bile acid sequestrants. Of these, I really only prescribe statins and Zetia today. And, there are now a plethora of new medications that do a better job of lowering heart disease risk. However, many are quite pricey, which is the downside.

Before I talk about the different types of cholesterol-lowering medications, I think it's important to note that the main reason we try to lower cholesterol is to reduce cardiovascular risk (e.g., heart attacks, strokes). It's important to note that some cholesterol medications do indeed improve cholesterol numbers, but have failed to show a benefit in clinical trial of lowering cardiovascular risk. For example, niacin, which we used to use all the time to raise someone's good cholesterol (HDL), is now not even recommended anymore because it doesn't improve cardiovascular outcomes and also leads several side effects (e.g., flushing of the skin). Other drugs may lower triglycerides, (e.g., fibrates) but have not been shown to lower cardiovascular risk.

Below, I will discuss some, but not all, of the types of cholesterol-lowering medications that the new cholesterol guidelines from ACC/AHA recommend to lower cardiovascular risk. I will not discuss side effects in this post, but rather just mechanisms of action and when to use each. I will reserve discussion on side effects for another post.

Statins are a class of drug that inhibit an enzyme in the liver called HMG-CoA Reductase. This enzyme is one of many that are needed for the synthesis (creation) of cholesterol in the liver. Since statins block this enzyme, they help prevent cholesterol formation in the liver. Statins get their name because all of the generic statins end in "-statin". E.g., atorvastatin, rosuvastatin, pravastatin, lovastatin, simvastatin. These drugs significantly reduce LDL (bad cholesterol) and significantly reduce the risk of heart attack and stroke. Now generic, statins are considered the first-line medications for lowering cholesterol because of how effective they are, and now also because they are generic and inexpensive. Statins can lower LDL bad cholesterol by up to 55%. You just can't achieve this level of LDL reduction with dietary changes alone. There is a lot of misinformation about statins online that make people not want to take them, but we'll discuss this in another post.

The next drug we'll discuss is ezetimibe (Zetia) Ezetimibe (Eh-zeht-ih-mybe) is the generic name and Zetia is the brand name. Ezetimibe works in the small intestine by decreasing cholesterol absorption from the foods we eat. By itself, ezetimibe lowers LDL cholesterol by 18%. It can lower the risk of heart disease but clearly not as effective as statins. It is best used in combination with statins or in those who report intolerance to statins.

A powerful, relatively new, class of cholesterol-lowering drugs are known as PCSK9 inhibitors. The way they work is complex--blocking an enzyme that degrades LDL receptors. LDL receptors are responsible for clearing LDL (bad cholesterol) from the bloodstream, so if more of these receptors are present, LDL levels in the blood can be lowered easier. These drugs are typically either given as subcutaneous injections (brand names Praluent and Repatha) or as intravenous infusions (brand name Leqvio). These drugs are quite powerful, lowering LDL up to 64%. They significantly lower cardiovascular risk. Likely due to their expense, they are typically now only used to prevent a second heart attack or stroke when statins are not enough to reach cholesterol goals. They are not used at this time to prevent a first heart attack or stroke unless a patient has a genetic condition called heterozygous familial hypercholesterolemia (HeFH).

The next drug to discuss is bempedoic acid (Nexletol). This is an ATP citrate lyase inhibitor. Similar to statins, bempedoic acid lowers LDL cholesterol by interfering with an enzyme responsible for synthesizing cholesterol in the liver. This is a newer drug that can reduce the risk of heart attack and stroke and lower LDL by about 24%. It is typically used currently to lower cholesterol in patients who either need additional cholesterol-lowering while on a statin or in those who cannot tolerate statins.

Finally, there is a drug that is used to lower triglycerides that also has been found to lower cardiovascular risk. Icosapent ethyl (Vascepa) contains EPA (a type of omega-3 fatty acid) and can lower cardiovascular risk. Over the counter fish oil (omega-3 fatty acid esters) also contains EPA but also contains DHA. The over the counter products can actually modestly raise LDL cholesterol and haven't been consistently shown to lower cardiovascular risk.