"This is a pretty clear failure. Physicians should now stop using ezetimibe or Vytorin except as a last resort." - Dr. Steven Nissen (Cleveland Clinic, OH)
"Dr. Nissen's suggestion about a moratorium on ezitimibe is rather alarmist, given that this was just an imaging study, and an imaging study should not change clinical practice." - Dr. Robert Harrington (Duke Clinical Research Institute, Durham, NC)
These 2 quotes pertain to the January 14th release of the ENHANCE study, a trial that evaluated the effects of ezetimibe + simvastatin (aka Vytorin) on preventing neck artery thickness. As you can tell, the announcement by the manufacturers Merck and Schering-Plough was disappointingly negative and has generated significant controversy.
Talk about timing. I just wrote my last article in early January on ezetimibe and how the liver safety of this medication when used in combination with a statin was called into question. One reason that many were suspicious about ezetimibe (Zetia) was that the ENHANCE trial had been long overdue in revealing its results. I doubt that this recent release of the results had anything to do with my article, but I would give credit to the scientists, congress, and the New York Times for applying pressure on the companies to act.
Neck artery thickening (ie plaque formation in the carotid arteries) is often used as a surrogate marker for the development of heart artery disease. If a medication can reduce or prevent carotid artery thickening, then there's a pretty good chance it will have the same effect in the heart arteries.
The ENHANCE study is of such importance because it is the first major trial of ezetimibe. There have been several smaller studies already published that prove ezetimibe's ability to lower LDL, and these studies were the reason why the FDA gave Zetia and Vytorin FDA approval in 2002. ENHANCE not only looked at LDL levels but also evaluated a surrogate clinical marker for heart disease. Unfortunately, ezetimibe + simvastatin were no better in preventing neck artery thickening than simvastatin alone despite markedly lower LDL levels. This would then imply that ezetimibe may not have any ability to prevent the development of heart artery disease.
Who is right? Dr Nissen who says we should stop using this medication right away or Dr Harrington who says this study does not provide enough information to stop taking ezetimibe? If you ask the American College of Cardiology, they would and have said, "Conclusions should not be made until the three large clinical-outcome trials are presented within the next two to three years. The ACC recommends that Zetia remain a reasonable option for patients who are currently on a high-dose statin but have not reached their goal. The ACC also notes that Zetia is a reasonable option for patients who cannot tolerate statins or can tolerate only a low-dose statin." Essentially, the ACC has sided with Dr. Harrington and has not advocated immediate withdrawal of ezetimibe. I think one thing is clear from this statement which echoes what I mentioned in my last article. Zetia is not a first line cholesterol lowering medication and should only be considered after maximizing statin doses.
One positive aspect from the ENHANCE study was that ezitimibe appears to be quite safe. There was no additional risk to liver or muscle when ezitimibe was given with a statin. At least ezetimibe is not physically hurting people, but financially it may be another story. A 1 month supply of Zetia or Vytorin costs ~$90 while a month's supply of generic simvastatin costs ~$30. I suppose we'll have to wait a little longer before we'll know if taking this medication is actually helping people other than the shareholders of Merck and Schering-Plough.
Published On: January 23, 2008