High Cholesterol: When Statins Don’t Work

Medically Reviewed by Jennifer Robinson, MD on July 18, 2023
5 min read

When your cholesterol is too high, you have a higher risk for a heart attack, stroke, and other chronic diseases. One of the best ways to lower your risk for related health problems is to get your cholesterol down.

The most common medicines doctors prescribe for this are statins. These prescription drugs lower your risk for heart disease by blocking a substance your body uses to make cholesterol.

But statins aren’t always enough. One study says that half of people who take statins don’t get their cholesterol down to a healthy level after 2 years. So, if you are one of those people, what should you do?

When statins don’t work, doctors sometimes call it statin resistance. True statin resistance is extremely rare. If you’re taking your statins, it’s unlikely that they aren’t working at all. But they may not work well enough. Here are some reasons you might not get the desired results.

You’re not taking them. If you think you might be resistant to statins, first ask yourself whether you’re really taking them as prescribed. If you’re not taking your pills as often as your doctor instructed, that’s likely why your cholesterol hasn’t dropped. Many people have trouble sticking to them. If there’s a chance the medicine isn’t working because you aren’t taking them or at least not like you should, the first thing to do is start.

Unpleasant side effects. Some people don’t take their statins because they cause side effects that are hard to tolerate. If unpleasant side effects have caused you to avoid your medicine or cut the dose, talk to your doctor about it.

Statins aren’t enough. If your cholesterol was very high to start, statins on their own might not be enough to get your cholesterol down to a healthy level. You and your doctor will need to come up with other strategies to add to your medication.

A very unhealthy diet. Statins alone may not be enough to lower your cholesterol if you eat a lot of foods that are high in saturated fats. A heart-healthy diet is a key part of cholesterol management.

You need more time. Statins don’t work instantly. If you just started taking them, your doctor will probably check at about 2 months to see if your cholesterol has gone down. They will keep checking until your cholesterol gets to a healthy level. If it seems like your statins aren’t working well enough but you haven’t taken them for very long, it might just be too soon.

You need a higher dose. Statins work best at a moderate to high dose. Your doctor might suggest you start taking a higher dose to see if that gets your cholesterol to budge.

Other health problems. Problems with your thyroid, liver, or kidneys can cause your cholesterol to go up even when you’re on statins. Your doctor can run blood and urine tests to see if there’s another health condition that you need to address.

You take other medications. Some medications can interfere with a statin’s ability to do its job. Make sure your doctor has a complete list of everything you take, including over-the-counter medicines, vitamins, and supplements. One of these drugs could be getting in the way of your statin.

Your genes. Scientists have linked true statin resistance to variations in many different genes. If your cholesterol doesn’t budge, your doctor might order genetic or other tests to look for causes of your high cholesterol and resistance to statins, but regardless, the important thing will be to find a way to get your cholesterol down.

If your doctor can’t find a way to make statins work for you, there are other medicines to try. First, you could try a different statin (or a statin combined with another drug in one pill) since there are several of them. But keep in mind, they all work in a similar way.

Next, your doctor may want you to try a different class of cholesterol-lowering medicine. These are other drugs that work in different ways:

  • Bile acid sequestrants keep your body from absorbing fat from the food you eat.
  • Cholesterol absorption inhibitors prevent your body from absorbing cholesterol from your food.
  • Niacin can help to lower “bad” LDL cholesterol.
  • PCSK9 inhibitors block a protein to help your liver get rid of “bad” LDL cholesterol.
  • Fibrates can increase “good” HDL cholesterol.

If your high cholesterol comes from a rare genetic disorder called familial hypercholesterolemia, there may be other treatments to try. These include:

  • Lipoprotein apheresis: A procedure to remove “bad” LDL cholesterol and lipoproteins from your blood
  • Bempedoic acid: Medicine that keeps your liver from making cholesterol in a different way than statins do
  • Lomitapide: Medicine that blocks an enzyme in your liver that makes “bad” LDL cholesterol
  • Liver transplant
  • Mipomersen (Kynamro): A cholesterol-lowering drug for people who have familial hypercholesterolemia
  • Inclisiran (Leqvio): is an add-on for those taking statins who require additional lowering of their LDL-C

Don’t forget that a healthy diet and exercise are important for reaching and maintaining healthy cholesterol levels even if you take statins. If statins don’t work well enough, think about what you’re eating.

Changes to your diet can help you lower your cholesterol.


  • Saturated fat, found in red meat, full-fat dairy products, and fried foods.
  • Trans fats, such as partially hydrogenated vegetable oils and margarines, sometimes found in packaged foods.

Eat more:

  • Omega-3 fatty acids found in fish and nuts.
  • Fiber from foods such as oatmeal, beans, fruits, and vegetables.
  • Whey protein, a healthy component of dairy.

In addition to a healthy diet, staying active can help to increase “good” HDL cholesterol. Other healthy lifestyle changes that may help lower your “bad” LDL cholesterol or increase your “good” HDL cholesterol include:

Your doctor has likely set a specific cholesterol goal for you. If you aren’t meeting that goal with statins, it’s important to consider your other risk factors for heart disease. The higher your risk, the more likely it is that your doctor will recommend you take more aggressive steps to lower your cholesterol.

For example, it’s especially important to get cholesterol down if you’ve had a heart attack or stroke already. It’s also extra important if you have lots of other risk factors, besides cholesterol, that increase your chances for a heart attack or stroke. Your doctor can help you understand your risks and what you should do next to protect your health.