Zetia Patients: Now What?
Millions of Americans are taking a drug that the ENHANCE (Effect of Combination Ezetimibe and High-Dose Simvastatin vs. Simvastatin Alone on the Atherosclerotic Process in Patients with Heterozygous Familial Hypercholesterolemia) trial found to have no benefits but may raise the risk of heart attack and stroke. The drug in question is Zetia™ and the ENHANCE trial was funded by two companies that manufacture Zetia™, Merck and Schering-Plough.
Zetia™ (brand name) or Ezetimibe (generic name) is a cholesterol-lowering medication that reduces LDL (bad) cholesterol by blocking absorption of cholesterol in the gastrointestinal tract (gut).
Zocor™ (brand name) or Simvastatin (generic name) is a cholesterol-lowering medication or statin that reduces LDL (bad) cholesterol by inhibiting cholesterol production in the liver.
Vytorin™ (brand name) or Ezetimibe-Simvastatin (generic name) is a combination of Zetia™ and Zocor™.
The ENHANCE trial, conducted by a group from the University of Amsterdam, lasted two years and involved 720 participants with heterozygous familial hypercholesterolemia (genetic condition that causes abnormally high levels of blood cholesterol). Participants in the trial were either given Zocor™ or Vytorin™. The study was primarily designed to determine if Vytorin™ would slow the growth of the inner lining (carotid intimal-medial layer) of the carotid artery. The measurement is called carotid intimal-medial thickness (IMT). An increased IMT can be associated with plaque (disease causing fat deposits) in the carotid arteries (which can, if it gets to a certain size, affect the supply of blood to the brain). The IMT measurement has been used in various small-scale studies. It should be noted that changes in IMT do not always predict how useful a medication can be in preventing heart attack or stroke.
- LDL cholesterol levels in participants taking Vytorin™ decreased by 58 percent, compared to a 41 percent decrease in participants taking Zocor™.
- The increase in the IMT was more in the Vytorin™ group than the Zocor™ alone group, but these results are not statistically significant and one can't make assumptions about this difference without seeing all the data.
Therefore, although Vytorin™ did reduce LDL cholesterol levels, participants who took this drug had a non-statistically significant increase in IMT whose significance remains to be determined.
*as currently released; full paper has yet to be published
Robert O. Bonow, MD is the chief of the Division of Cardiology, co-director of the Bluhm Cardiovascular Institute at Northwestern Memorial Hospital, and the Goldberg Distinguished Professor at Northwestern University's Feinberg School of Medicine. Dr. Bonow stated on a recent "Eye on Health" segment on CBS News in Chicago, "There is no evidence of harm [with using Vytorin™], but since the trial showed no evidence of benefit either, these results could change the prescription patterns [for Vytorin™] in a major way. "We need to wait for the results of the larger ongoing clinical trials to know whether Vytorin™ changes the outcome of patients, in terms of death, heart attack, and stroke, in a beneficial way or whether there are any safety concerns." Dr. Bonow also stressed that patients on Vytorin™ should not panic and should not stop taking any medication until they talk with their physician.
For more detailed information, Dr. Bonow worked with the American Heart Association (AHA) to publish "Do Recent Trials "Enhance" Our Understanding of Cholesterol Treatment?"
The American College of Cardiology (ACC), a leading professional society for cardiologists, released a public statement on the ENHANCE trial explaining:
- Physicians and patients should not make major clinical decisions on the basis of the ENHANCE study alone
- This is not an urgent situation and further research is needed in this area to provide conclusive evidence about which lipid lowering strategy is preferred
- Zetia™ remains a reasonable option for patients who are currently on high dose statins but have not reached their [LDL] goal.