You Asked:

I take Vytorin to lower my cholesterol. In the news this week there have been articles saying that this drug may cause cancer. Should I stop taking it?

Dr Ockene answers:

In the news recently there has been considerable discussion of a possible increase in the risk of cancer related to the lipid-lowering drug Vytorin, and in particular to one component of this medication. Vytorin is a combination of two medications:Zocor, a well tested statin which has been available for over two decades and is now, as simvastatin, available generically, and Zetia (ezetimibe) a more recently developed drug that has a totally different mechanism of action. Zocor, along with other statins, works by blocking cholesterol manufacture in the liver.  Zetia does not have any effect on the liver, but blocks the absorption of cholesterol in the intestine. It does this by interfering with the mechanism whereby cholesterol is brought across the intestinal lining into the blood. Zocor has been shown to be both safe and effective in studies involving tens of thousands of individuals in controlled clinical trials. Large-scale controlled trials of Zetia are now ongoing, but the drug was approved by the Food and Drug Administration on the strength of its ability to lower cholesterol levels and its apparent safety in preliminary testing.

The controversy originated with an article in the New England Journal of Medicine published online (many of the journals now publish important articles over the Web before they appear in print) that studied the value of treating aortic stenosis - a narrowing of the aortic valve (the outflow valve of the heart) - with lipid-lowering medication, specifically, in this study, Vytorin. The study showed no effect of this type of therapy on the valve narrowing. This by itself is not especially surprising as this condition leads to heavy calcium deposits in the valve and it was, in my opinion, a bit of a long shot to think that lipid-lowering therapy would be of value. But more surprising was the finding that cancer occurred more frequently in the group that received the active drug as compared to the placebo group. Because this was such an important and unexpected finding, the paper was accompanied by two other papers in that issue of the journal. In the first,  Richard Peto, one of the world’s most respected statisticians, carried out an analysis looking at both this study and two other larger studies using Zetia, and concluded that there was no clear evidence that Zetia has a real relationship to cancer. But in an accompanying editorial the editors of the New England Journal of Medicine raised a cautionary note suggesting that one could not entirely dismiss the issue, and further information was needed.

So where does this leave us? Other studies using this drug are in progress, and will provide us with more certain answers. At the moment, the evidence relating Zetia to cancer is of some concern but far from clear. So here is what I think. In all of medicine we are constantly balancing risk against benefit. We use drugs that have possible side effects, sometimes potentially serious, because the expected gain is greater than the risk. How do we apply this to Zetia? We should not use Zetia, or the combination drug Vytorin, as first-line therapy. But it is totally reasonable to use it when the gain clearly exceeds the risk. In patients who already have known atherosclerotic disease, be it heart disease, stroke, or vascular disease in the legs or other arteries, or who are at very high risk of disease because of a combination of risk factors such as diabetes, smoking, and high blood pressure, there are times when we cannot achieve a low enough cholesterol level despite maximum use of statin therapy. In such patients adding Zetia is appropriate. We also see patients who are intolerant of every statin and simply cannot take them. Here too Zetia is a useful drug. Of course, every patient is different and if you are taking either Vytorin or Zetia you should discuss it with your physician.

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