The ENHANCE study is controversial because, while the study was concluded in early 2006, the release of its results was famously delayed until early 2008. As noted elsewhere, some have claimed that the reason for the delay was that the trial did not come out the way the sponsors wanted it to, and they were trying to salvage something positive before releasing the results. The sponsors and investigators have denied this claim, but Congress has indicated an interest in investigating this matter.
The ENHANCE study enrolled 720 patients who were randomized to receive either Vytorin, or Zocor alone. As an endpoint, investigators looked at the growth of plaques on arterial walls using non-invasive ultrasound imaging. The trial was expected to show that patients on Vytorin would have less plaque growth than patients taking Zocor alone.
However, the data actually showed no benefit for Vytorin over Zocor. In fact, while the results were not statistically significant, patients on Vytorin had more plaque growth than patients taking only Zocor. (The arterial wall thickness increased by 0.0111 mm for Vytorin, but only by 0.0058 mm for simvastatin alone -- a ratio of nearly 2 to 1.) There did not appear to be any difference in side effects, or in the incidence of cardiovascular events among the two groups.
There has been a lot to draw the public's attention here, including a) the alleged hanky-panky in manipulating the data; b) the delay of 2 years in releasing the data (during which the sponsors were selling an estimated $5 billion in Zetia and Vytorin); c) the interest Congress has already shown in the behavior of the sponsors, and d) the resulting inflammatory statements in the press. (The famous pharmaceutical gadfly Dr. Nissen, for instance, was quoted in the New York Times as saying that the results are shocking, that nobody should be taking these drugs unless all other cholesterol drugs have failed, and that taking these drugs will increase their risk). As a result, it is exceedingly likely that patients now taking Zetia and Vytorin will, at the very least, have lots of questions for their doctors.
It is worth noting, therefore, that the results reported so far for the ENHANCE trial should not be immediately alarming. There is no evidence of worse clinical outcomes for patients taking Vytorin. Furthermore, while the plaques appeared to grow more for patients in the Vytorin group than in the Zocor group, in fact plaque growth was very small in both groups.
The bottom line is that this study appears to show no compelling reason for patients to take either Zetia or Vytorin, at least unless their cholesterol levels cannot be controlled with other measures. But at the same time, being on the drugs right now is not something that needs to be dealt with as an emergency. Talk to your doctors about whether you really need to be on them.
The biggest widespread harm caused by Vytorin, judging from the data available so far, is probably to pocketbooks -- Vytorin is far, far more expensive than Zocor alone, at least in its cheap generic form (simvastatin). And while it's probably not a "harm," those commercials comparing your Uncle Harry to a plate of pancakes and eggs are among the most annoying I've seen. Thankfully we've seen the last of them.
The most important implication the ENHANCE trial is not the damage it has done to the market viability of Vytorin and Zetia, but instead, the damage it has done to the notion that lowering cholesterol is important in the first place. The question of how useful it is to reduce cholesterol levels, in light of the ENHANCE trial results, is discussed here.
You can read more about statins, and why they are useful in reducing cardiac risk, here.
Source:
American College of Cardiology Statement on the ENHANCE trial: http://www.acc.org/enhance.htm.
