News & Reviews

ENHANCE Study Suggests no Benefit from Vytorin

by Tori Vahle, Pharm.D.

Should I stop taking Vytorin? Many patients are now asking this question. Vytorin is a medication used to treat high cholesterol levels and has received much attention from the media recently due to the results of a study called the ENHANCE study. This article will help you understand what we can learn from this study.

Cholesterol comes from two sources: our bodies and the foods we eat. Most of us have seen advertisements for medications that lower cholesterol. Some medications, such as Lipitor (atorvastatin) and Zocor (simvastatin), work by preventing the body from making cholesterol. These medications are often called ?statins?. Another kind of medication, Zetia (ezetimibe), works in a different way. It blocks cholesterol from being absorbed from the foods we eat. Vytorin is a combination medication that includes both a statin (simvastatin) and ezetimibe in one pill. Vytorin decreases levels of low-density lipoproteins (LDLs). LDLs are often referred to as "bad cholesterol" because they carry cholesterol to the body?s tissues, including the arteries. Elevated levels of LDLs can lead to heart disease.

Previous studies have shown that lowering LDL cholesterol reduces the occurrence of cardiovascular events such as heart attacks and strokes. Studies have also shown that statins can only lower the LDL by a certain amount. For some patients, a lower LDL is needed. Because it combines a statin with ezetimibe, Vytorin has been thought to be more beneficial than statins alone in patients who require additional LDL-lowering. However, the results of the ENHANCE study have led some people to question the benefit of Vytorin over statins alone.

The ENHANCE study took place from 2002 to 2006 and included over 700 participants. In the study, participants were treated with either simvastatin plus ezetimibe (Vytorin) or simvastatin alone. All participants in the study had a specific condition called heterozygous familial hypercholesterolemia. This is a condition that is inherited, meaning it is passed down through families. People with this condition have a very high LDL. Only 1 in 500 people have heterozygous familial hypercholesterolemia. Most people that take medication to lower their cholesterol do not have heterozygous familial hypercholesterolemia.

The goal of ENHANCE was to find out if the combination of simvastatin plus ezetimibe could reduce atherosclerosis more than simvastatin alone. Atherosclerosis is the build-up of fatty material (plaque) inside the arteries. Plaque is thought to be made up of fat, calcium, and cholesterol, and can collect in any blood vessel. To find the change in atherosclerosis, scans of large arteries in the neck were completed. The study investigators then compared the scans from those patients taking simvastatin plus ezetimibe to those taking simvastatin alone. They found no differences in the scans between those taking the combination and those taking simvastatin alone. This means that, in this study, the combination of simvastatin plus ezetimibe was no better than simvastatin alone at reducing the size of plaques that could lead to atherosclerosis.

However, the study looked at other key factors. It compared changes in LDL levels which also are associated with atherosclerosis. Those taking the combination had a greater reduction in their LDL than those taking simvastatin alone. The study also looked at adverse events resulting from the medications. It found no difference in the number of adverse events for those taking the combination compared to those taking simvastatin alone.

There are still many questions concerning Vytorin. Although the study collected data on deaths and cardiovascular events such as heart attack and stroke, the study was not large enough and was not designed to determine if there was a difference in these. Also, all the participants in the study had heterozygous familial hypercholesterolemia. Therefore, the findings of the study may not apply to patients with high cholesterol that is not a result of this rare genetic disorder

Although the ENHANCE study is complete, the data are still being analyzed and further reports about the study are expected. Larger studies that look at heart disease, death, and stroke will help us better understand the benefit of taking ezetimibe in combination with statins. Importantly, Vytorin still works to lower bad cholesterol levels and has not been shown to be unsafe. Patients taking Vytorin should not stop the medication on their own. If you have concerns about taking Vytorin, you should discuss them with your doctor.

References:

Kastelein J et al. Simvastatin with or without ezetimibe in familial hypercholesterolemia. N Engl J Med 2008;358:1431-43.

Citkowitz E. Familial Hypercholesterolemia. EMedicine. http://www.emedicine.com/med/TOPIC1072.HTM. Accessed April 7, 2008.