One of my commitments is to tell you what's what about the health stories circulating in the media. And, boy, did we have a doozie recently, with the hysteria surrounding some supposedly very disappointing study results concerning ezetimibe, a cholesterol-lowering agent included in the popular drugs Zetia® and Vytorin®.

If are now taking either Zetia and Vytorin for high LDL levels, and you've read some of these rather inflammatory news stories, let's see if I can clear the air and put your mind a little more at ease.

In January, a press release announced results of a study of ezetimibe. News reports quickly followed, some of which told us that arterial plaque actually grew twice as fast in patients who received ezetimibe, compared to those who received a statin. One prominent cardiologist called the study results "shocking" and implied that ezetimibe could be raising the heart-attack risks of millions of people.

Sadly, this was yet another example of the media's hype extending far beyond the logical conclusions that could be drawn from the evidence.

The study in question, called ENHANCE, compared the statin Zocor® (simvastatin) to Vytorin® (a drug that combines simvastatin and ezetimibe), in hopes of answering the question of whether addition of ezetimibe helps to reduce atherosclerotic plaque more than simvastatin alone.

However, there are several reasons why the ENHANCE study can't be used to determine ezetimibe's effect on heart attack risk:

• A very small study sample. Only 720 patients, 357 in one treatment group and 363 in the other, participated in the study. Would you take a new drug if it had been found to be safe and effective in only 360 or so people worldwide? Or, should you stop taking a drug if only one study raised concerns in a population this small?
  
• Non-representative study sample. All of the subjects in the study had a rare genetic condition called familial hypercholesterolemia (FH), which is characterized by very high cholesterol levels and the early occurrence of heart attacks, usually by age 40. The average initial LDL cholesterol level in this study was 318, whereas most people have LDL levels well below 200. If a medication works in the sickest, hardest-to treat-patients, that certainly speaks volumes in its favor. But ezetimibe's failure to reduce plaque formation in this group does not necessarily mean the medication has no value, especially in people with less severe elevations of LDL.
  
• Heart attacks weren't studied. ENHANCE measured plaque thickness in the carotid artery - the main artery in the neck. We know that if a person has plaque in the carotid artery, chances are they also have it in one or more coronary artery. And we know that plaque in the coronary arteries (the arteries around the heart) is a major factor in heart disease. However, it is not safe to assume that failure of ezetimibe to reduce carotid plaque automatically means a higher risk of heart attack. That crucial medical question is still being studied in a much larger population of about 10,000 people, with results expected around 2011.

In the end, only one significant difference was found between the two groups of participants in ENHANCE: The patients treated with the combination simvastatin plus ezetimibe had significantly greater reductions in their LDL than those on simvastatin alone. The two groups' rates of heart attacks, strokes, and medication side effects were all comparable.

And here's what the media got a hold of that scared a lot of people unnecessarily: The thickness of the carotid artery walls in patients on simvastatin plus ezetimibe increased by 0.011 mm (about 4 ten-thousandths of an inch), while those in patients on simvastatin alone increased by 0.006 mm (about 2 ten-thousandths of an inch). While this near doubling of the plaque thickness may look scary to a lot of people, statistical analysis showed that no real differences exist between these two numbers.

In fact, there was another finding that might have implied a protective benefit for ezetimibe: There were twice as many cases of severely elevated muscle enzymes (a well known side effect of statins) in patients receiving simvastatin alone than in those on the combination treatment. But this was also shown statistically to represent nothing more than random chance.

In summary, the ENHANCE trial tells us that in a very small group of people genetically predisposed to have extraordinarily high levels of LDL cholesterol, adding ezetimibe to simvastatin helps to reduce the LDL level, but has no effect at all on carotid plaque growth. It also suggests that ezetimibe is as safe as simvastatin in this population.

We have known for many years that ezetimibe is a powerful tool for helping to lower LDL. We still don't know if that translates into reduced risk of heart attack for the average person with modestly or severely elevated LDL, and ENHANCE tells us little, if anything, about that risk

For treating high LDL cholesterol, I think it makes sense to prescribe the highest safe dose of statin that a patient can tolerate. But, based on the information available currently, I won't hesitate to add ezetimibe if the LDL is still above goal.