The American College of Cardiology (ACC) has issued a statement yesterday, 15th January, asking patients taking the cholesterol busting drugs Zetia (ezetimibe) and Vytorin (ezetimibe and simvastatin combined) not to panic and to talk to their doctors about the impact of the disappointing trial results on their treatment.
The statement follows news released on Monday, 14th January, by drug companies Merck and Schering-Plough Pharmaceuticals, that the ENHANCE trial testing the effect of Vytorin (ezetimibe and simvastatin combined) against an older drug, now available in generic form, Zocor (simvastatin alone), showed that the combination drug Vytorin, which is quite expensive, was no better at reducing artery clogging than the older and cheaper statin.
ENHANCE stands for Effect of Combination Ezetimibe and High-Dose Simvastatin vs. Simvastatin Alone on the Atherosclerotic Process in Patients with Heterozygous Familial Hypercholesterolemia.
The ACC said the study deserves “serious thought and follow-up”. The overall rate of cardiac events was nearly the same in both drug groups, and both drugs were generally well tolerated, they said. The differences in mean change in the intima-media thickness (IMT) between the Zocor (simvastatin) and Vytorin (ezetimibe and simvastatin) group was 0.006 versus 0.011 mm. IMT is a measure of the thickness of artery walls, and changes in this measure shows how much plaque has built up.
They said patients should not stop taking the drug on the basis of these results, the situation is not urgent, and they should talk to their doctor about any concerns they have. More research is needed before firm conclusions can be made about the risks and benefits of statin alone versus statin plus ezetimibe, said the ACC.
720 patients with heterozygous familial hypercholesterolemia (inherited high cholesterol from one of their biological parents) participated in the ENHANCE study. Over the two years of the study, there was no significant difference in the ability of the two drugs to slow the growth of plaque in carotid arteries supplying blood to the brain.
When news of the trial was released, there were several media reports saying that the trial showed there was no benefit from the more expensive combination drug Vytorin compared to simvastatin alone, which is now available as a much cheaper generic (used to be known under the brand Zocor).
But the ACC recommended in a press release that “major clinical decisions not be made on the basis of the ENHANCE study alone”.
They also noted that the trial is an imaging study (looking at the thickness of the artery walls), and was not designed to assess clinical outcomes. Final conclusions should not be drawn until three larger trials, which are assessing clinical outcomes, publish their results within the next two or three years, said the ACC.
The ACC recommends that Zetia (ezetimibe) is still a “reasonable option for patients who are currently on a high dose statin but have not reached their goal”. It is also a reasonable option for patients with low tolerance for statins, or who can only tolerate a low statin dose.
Meanwhile the market has reacted to the news of the ENHANCE trial. Shares in Schering-Plough, who make Vytorin, which accounts for two-thirds of the company’s profits, fell for a second day running yesterday, Tuesday. Analysts are saying the more expensive combination drug offers no real benefits over the cheaper statin only version, and that doctors will now think twice before prescribing it.
Another issue that is being reported in connection with this trial is the possibility that the drug companies may have sat on the results. The two year trial ended in April 2006. According to a report by Reuters news agency, Congress is planning to investigate how the two companies handled the release of the study’s results, calling the delay a “suspiciously long time”.
Sources: ACC press release, cardiosource.com, Reuters.
Written by: Catharine Paddock