The FDA swallows drug company hype without thinking

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Vytorin is a drug which combines the statin simvastatin with ezetimibe – a drug which blocks cholesterol absorption in the gut. To date, there has been no good evidence that ezetimibe reduces the risk of, say, heart attacks and strokes, but that has not stopped doctors feverishly penning prescriptions for this drug. The fact is, the drug reduces cholesterol, so it must be beneficial, surely (despite the glaring lack of evidence to support this).

The latest ezetimibe-related trial concerned people with chronic (long term) kidney disease – the so-called ‘SHARP’ trial. Compared to placebo, simvastatin and ezetimibe in combination was found to reduce the risk of cardiovascular events (such as heart attacks, strokes and the need for stenting of coronary arteries) by 16 per cent. I critiqued this study short after its publication here.

The results of this study were reported very positively, and put ezetimibe in a better light than before: at last a positive result for this drug! But as I pointed out, this study showed nothing of the sort. And that’s because individuals taking the active treatment took ezetimibe alongside simvastatin, and the result of this was compared with those from taking a placebo. How do we know if the benefits seen were due to simvastatin, ezetimibe, or both these drugs in combination? The answer is we don’t.

Previous studies have found, by the way, that while adding ezetimibe and simvastatin taken together reduce cholesterol more than simvastatin alone, this does not improve outcomes (and some evidence suggests worse outcomes, actually).

One way of avoiding the emergence of yet more embarrassing data that may hurt share price is to design studies such as that ezetimibe and simvastatin is not pitted against simvastatin alone (à la the SHARP trial).

I read recently that the Food and Drug Administration (FDA) in the US has given the thumbs up to Vytorin (remember, a combination of ezetimibe and simvastatin) to be used for patients with chronic kidney disease. If I was making the decisions about this sort of thing I’d reject the drug company’s (Merck) application and say:

“I know you’ve spent a lot of time and money on this study, but it fails to answer two critical questions:

  1. Is Vytorin better than simvastatin alone for individuals with chronic kidney disease?
  2. Is simvastatin better than placebo for individuals with chronic kidney disease?

Please go away and repeat this study but this time do it properly: include a group taking simvastatin alone, and then we’ll be able to answer these two critical questions.”

While reading about the FDA’s decision on Vytorin I came across the press release sent out by the researchers responsible for the SHARP trial which you can read here. Here’s an extract from it that leapt out at me:

The SHARP results are also relevant to people who don’t have chronic kidney disease. The combination of ezetimibe and a statin produced similar benefits to those resulting from the same LDL cholesterol reduction achieved with a high dose of a statin. Since the lower the cholesterol the bigger the risk reduction, these results suggest that patients who remain at high risk of major atherosclerotic events despite maximal statin therapy may benefit further from adding ezetimibe to their current statin regimen.

But as we know, the results of the SHARP trial simply cannot be used to support such a claim, and remember we have results of previous studies which directly contradict this assertion. As Larry Husten of the CardioBrief blog put it here,

It’s a model of a press release that tries to manipulate the reader to adopt its view of the trial and ruthlessly suppresses all information and perspective that doesn’t support its view.

It’s another example of scientists taking a distinctly unscientific approach. And it’s another example of a drug regulation authority making a bad decision. See here for more on this.

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