Ezetrol: Canadian Version of Zetia Questioned

Toronto, ONAs if the Zetia and Vytorinissue wasn't enough of a frustration on its own, north of the border in Canada the Canadian equivalent of Zetia—Ezetrol—is proving just as mystifying. At issue: does the cholesterol drug work? Is it harmful? And did the manufacturer, as it was accused of doing in the US, withhold important safety and efficacy information in an effort to protect sales?

Ezetrol is, in reality, the cholesterol drug Zetia wrapped in Canadian colors, and marketed and sold by the Canadian subsidiary Merck Frosst/Schering Pharma GP.

Like Zetia, Ezetrol is ezetimibe, a cholesterol drug that was designed to lower LDL, the so-called bad cholesterol that proves such a threat for heart attack and stroke.

The problem: allegedly, the jury is still out on the effectiveness of ezetimibe as a stand-alone cholesterol fighter. As is the case with Zetia in the United States Ezetrol, a non-statin, is most often prescribed in combination with a statin drug—usually, Zocor. The latter was morphed into the hybrid drug Vytorin, which combines Zetia with Zocor in a single pill.

Vytorin is not available in Canada, so patients are most often doubled up on both Ezetrol (ezetimibe) and Zocor (simvastatin).

This is where it gets just as confusing for Canadians, as it does for Americans. Vytorin, an expensive cholesterol drug, is marketed as an effective means to lower the harmful cholesterol that often results in heart attack and stroke. However, a long-delayed study known as ENHANCE revealed that the combination of Zetia and Zocor failed to reduce the growth of fatty deposits in the arteries. In fact, more patients appear to have exhibited a higher level of arterial plaque growth with Vytorin, than those just taking the statin Zocor alone.

The results would be equally representative in Canada, for patients on a combined therapy of Zocor and Ezetrol.

Zocor (simvastatin) is a statin drug, which lowers cholesterol in a different fashion than Ezetrol. While ezetimibe has not proven to ward off heart attack and stroke from arterial plaque build-up on its own, statins have. Statins appear to be the steady Freddie of the cholesterol world. They appear to reduce fatty plaque, and lower the risk for heart attack and stroke all by themselves, thank you.

What's more, statins are much less expensive.

Thus, while the effectiveness of statins has long been confirmed, the efficacy of Ezetrol as a stand-alone has long been disputed.

To add further fuel to the fire, a researcher with the US Food and Drug Administration (FDA) concluded in 2002 that Zetia (Ezetrol in Canada) should not be approved for use with statins as it was found, in combination with Zocor, to pose a risk for liver damage.

Zetia was approved anyway.

Much of the previous data suggesting problems remained unpublished. However, the pivotal ENHANCE study was intended to shed new light on those issues, as well as the ultimate effectiveness of Vytorin, or the combination of Ezetrol and Zocor.

When the study was finally released about two years after it was completed (and only at the behest of Congress, which urged the release of the document in the strongest of terms), the results were not kind to Vytorin, or the Ezetrol-Zocor combination in Canada.

In sum, it has been reported that the combination of Ezetrol and Zocor was not shown to be any more effective in lowering cholesterol levels, than taking a less-expensive statin such as Zocor, on its own.

A further study to determine if Ezetrol and Zocor taken in combination would prevent heart attacks and strokes is not due for completion until 2011. The nine-year lag between initial approval of Ezetrol and the next study yet to be completed should, one would assume, represent healthy profits for the manufacturer.

And that's the point. Many are crying foul that in delaying the results, the manufacturers of Ezetrol/Zetia/Vytorin were promoting an allegedly false impression that the drug was both safe and effective. In comparison, taking a statin could potentially be a safe, effective and decidedly less-expensive alternative.

It is interesting to note that in spite of its own reviewer recommending Zetia (Ezetrol) not be cleared for use with statins, the FDA approved it anyway—even though pre-market clinical trials involving 3,900 patients over a 12-week window concluded that 11 times as many patients who took Ezetrol (Zetia) in combination with a statin had developed serious health difficulties, compared with those who only took a less-expensive statin.

In 2005 both Canada and Australia issued warnings regarding Zetia (Ezetrol in Canada) and the drug's potential to cause hepatitis, pancreatitis and depression.

Such warnings have largely hovered under the radar in the US.