Previously, I have written about the drug combination of simvastatin and ezetimibe (sold as Vytorin in the US). Both of these drugs reduce cholesterol, but through different mechanisms. Taken together, these drugs do do a good job of reducing cholesterol levels And we all know that the lower we get the cholesterol levels down the better, right? Well, actually, results show that Vytorin did not work to halt the progression of the ‘plaques’ that gum up arteries and can precipitate heart attacks and strokes.

And then another thing is that giving people simvastatin and ezetimibe is associated with an increased risk of death due to cancer. This finding was inexplicably waved away by scientists as a chance finding (even though the statistics showed that the finding was very unlikely to be due to chance).

Anyway, this week sees more bad news for the manufacturers of Vytorin and also those who take it. The New England Journal of Medicine has just published a study in which individuals on a statin were additionally treated with ezetimibe or niacin (vitamin B3) over 14 months [1]. All of the individuals in the trial had either been diagnosed with heart disease or were deemed to be at high risk of this condition.

The researchers measured a number of parameters including:

LDL-cholesterol (a form of cholesterol said to be associated with a higher risk of cardiovascular disease)

Carotid artery intima thickness (the thickness of the wall of the major blood vessel supplying blood to the head – increased thickness is generally taken as a sign of worsening cardiovascular disease risk)

In the group taking a statin and ezetimibe, LDL, HDL and triglyceride levels went down.

In the group taking a statin and niacin, LDL and triglyceride levels went down, and HDL levels went up.

On paper, at this point, the group taking the niacin and statin fared better. However, more important than these results were those relating to the carotid artery intima thickness. Guess what? The group taking the niacin did better than the group taking ezetimibe on this score too.

One other outcome the researchers kept tabs on was ‘major cardiovascular events’ such as heart attacks and strokes. Here again, the niacin group fared better – 1 per cent of them had such an event compared to 5 per cent in the group taking ezetimibe.

The New York Times reports here that Dr Peter Kim, the president of Merck Research Laboratories (makers of ezetimibe) claimed that the study was limited because it did not compare the groups of patients taking a statin and a second drug to a placebo group. He also claims that a drug’s ability to improve artery-wall thickness has not been proved to automatically correlate with a reduction in heart attacks. Moreover he stated that ezetimibe lowers bad cholesterol and lowering bad cholesterol is a “known good”.

Ezetimibe has been licenced on the basis of its ability to reduce LDL-cholesterol – something that is referred to as a ‘surrogate marker’. So, Merck it seems that Merck is happy for its drug to be sold and promoted on the basis of one surrogate marker (reduced cholesterol), but none-too-keen for its drug to be criticised on the basis of another surrogate measure (carotid artery intima thickness).

Dr Kim also describes a reduction in bad (LDL) cholesterol as a “known good”. However, the new England Journal of Medicine study found that lower levels of LDL cholesterol were actually associated with an increase in carotid artery intima thickness. And never mind this, do we really think that just because something reduces LDL cholesterol levels, that has to be a good thing. I mean, if arsenic and cyanide were found to reduce LDL cholesterol levels, would that mean we should all be taking arsenic and cyanide every day?

The New York Times article also quotes Dr James Stein, professor at the University of Wisconsin medical school, who points out that as far as ezetimibe is concerned, “there is not a shred of evidence that it does anything good for blood vessels or heart disease.”

References:

1. Taylor AJ, et al. Extended-Release Niacin or Ezetimibe and Carotid Intima–Media Thickness NEJM 15th November 2009 [epub ahead of print]

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