High cholesterol levels: Can ezetimibe lower the risk of complications?

There is not enough research on whether people with high cholesterol levels have a benefit by taking ezetimibe in addition to a statin. There is not enough data on adverse effects of ezetimibe.

Cholesterol is important for our body: it is needed for producing certain hormones and building cell walls, for example. The body produces most of this cholesterol itself, but we get some from the food we eat. Chemically, cholesterol is part of the substance category containing mostly water-insoluble lipids. Sometimes it is also incorrectly called “blood fat”, because it is part of the same chemical group as fats.

Some people have high cholesterol levels in their blood (hypercholesterolemia). This can be caused by different things. For example, the liver may not be able to take in cholesterol due to a predisposition. Conditions such as diabetes mellitus or thyroid gland problems can also contribute to hypercholesterolemia.

Having high cholesterol levels is considered to be a risk factor for cardiovascular disease

High cholesterol levels in the blood do not cause any symptoms. But they are considered to be a risk factor for complications like heart attacks and strokes.

Eating more fruits and vegetables and getting more exercise are common recommendations for lowering the risk of cardiovascular disease. There are also different drugs available for lowering cholesterol levels in the blood. They are often used if changes in diet or exercise do not change cholesterol levels enough. But high cholesterol levels do not always need to be treated. This depends on other things, for example whether someone has additional risk factors.

The statins are the largest group of cholesterol-lowering drugs. Some statins, for example simvastatin, have been proven to lower the risk of cardiovascular disease and to increase life expectancy. You can read more about this here. There are also some other less common cholesterol-lowering drugs, such as niacin and fibrates. Compared to statins, there is less evidence of their benefit.

Lowering cholesterol levels with drugs does not always have an advantage

Ezetimibe is a newer drug that can be used for treating high cholesterol levels. It blocks cholesterol from entering the bloodstream from digested food and bile. This drug is taken daily in tablet form. It is usually used together with a statin. People who do not tolerate statins, or who do not take them for other reasons, can also take ezetimibe without a statin.

Ezetimibe can lower cholesterol levels. But this does not automatically mean that people who have high cholesterol levels will also have a benefit. That is because most metabolic processes in the body are so complicated that just one factor on its own cannot predict anything about the benefit of a particular treatment. Just because a drug lowers the cholesterol levels does not automatically mean that it can lower the risk of heart attacks or other complications. You can find out more about how reliable trials are designed here.

To find out whether people who have high cholesterol levels can profit from ezetimibe, researchers from the German Institute for Quality and Efficiency in Health Care (IQWiG) – who publish this website – looked for trials on this drug together with the Institute for Pharmacology at Bremen-Mitte Hospital (Germany).

The benefit of ezetimibe is not clear

The researchers found two trials testing ezetimibe in combination with a statin. In one of these trials ezetimibe was compared with a dummy drug containing no active ingredient (placebo). In the other it was compared with a different cholesterol-lowering drug (niacin), each in combination with a statin. Just under 1,100 people took part in both trials. The first trial lasted 14 months, the other 24.

Neither of these trials was designed specifically to test whether ezetimibe lowers the risk of cardiovascular disease. They mostly looked at how the drug affects the thickness of the blood vessel walls. The simple fact that a drug influences the thickness of the blood vessel walls does not automatically mean that it also lowers the risk of complications. The trials did take note of how often heart attacks, strokes and other types of cardiovascular disease occurred, as well as what adverse effects the drug had. But the trials did not have enough people to produce reliable answers to these questions.

So it remains unclear as to whether ezetimibe can lower the frequency of cardiovascular disease if it is used together with a statin. The trials showed no benefit of ezetimibe regardless of whether it was compared with niacin or with a placebo. A larger trial involving more than 18,000 people is now being carried out that aims to find out more about the advantages and disadvantages of ezetimibe. When the results of this trial are made available, we will have information about it on these pages.

Author: Institute for Quality and Efficiency in Health Care (IQWiG)

Note

This health information is a summary of a scientific report published by IQWiG. It is not an assessment of the right to have health care services paid for by statutory health insurance funds in Germany. By law, decisions about paying the costs for diagnostic and therapeutic procedures can only be made by the German Federal Joint Committee (G-BA). The Federal Joint Committee takes IQWiG reports into consideration in its decision-making process. You can find information about the decisions of the German Federal Joint Committee on its English-language website, www.english.g-ba.de.

© IQWiG (Institute for Quality and Efficiency in Health Care)