Ezetimibe: What's The Real Score?

The New York Times explores lingering issues about ezetimibe.

When the Food and Drug Administration approved a new type of cholesterol-lowering medicine in 2002, it did so on the basis of a handful of clinical trials covering a total of 3,900 patients. None of the patients took the medicine for more than 12 weeks, and the trials offered no evidence that it had reduced heart attacks or cardiovascular disease, the goal of any cholesterol drug.

The lack of evidence has not stopped doctors from heavily prescribing that drug, whether in a stand-alone form sold as Zetia or as a combination medicine called Vytorin. Aided by extensive consumer advertising, sales of the medicines reached $5.2 billion last year, making them among the best-selling drugs in the world. More than three million people worldwide take either drug every day.

But there is still no proof that the drugs help patients live longer or avoid heart attacks. This year Vytorin has failed two clinical trials meant to show its benefits. Worse, scientists are debating whether there is a link between the drugs and cancer. ~ NYTimes, 1 Sept 2008

$5.2 billion in sales? That's a lot of money. The medical sales people are doing a good job of marketing this medicine to both doctors and patients. But I wonder how many doctors and patients really know the controversies surrounding ezetimibe?

Aside from great advertising and the "irresistible" charms extended by medical representatives on doctors to prescribe their pharma companies' medicines, what is the reason why ezetimibe is a bestseller today when its effectivity is still in question?

According to the same NYTimes article, the answer lies in a term called "surrogate endpoints."

Many medicines are approved on the basis of what scientists call surrogate endpoints, like proof that they lower cholesterol, rather than because they have been shown to reduce the risk of death or disease.

For example, a cancer drug might be approved because it causes tumors to shrink, not because its manufacturer can prove that patients live longer after taking it.

Using these measures makes sense in certain circumstances, researchers say. If no treatments exist for a disease, the F.D.A. may approve a drug based on its promise in short-term trials and hope that the medicine succeeds later in larger trials where its potential to reduce death and disease will be examined directly.

Here in the Philippines, I vividly remember when a famous local cardiologist heaped praises upon praises on the wonderful ways ezetimibe lowers bad cholesterol during its drug launch. And because it does, it becomes the new medicine to trust to prevent heart attacks and improve one's lipid profile. I need not wonder if his speech worked or not; the drug sales figures should speak for itself.

But what about long-term safety? That takes a back-seat now. It will only get noticed when more people complain about observed adverse side-effects. Meanwhile, the cash register keeps on ringing.

What about the ezetimibe-cancer link? Yesterday, the New England Journal of Medicine released a report online published weeks ahead of its schedule. Using data collected from 3 ezetimibe trials (SEAS, SHARP, and IMPROVE-IT), it came up with this  conclusion: 

The available results from these three trials do not provide credible evidence of any adverse effect of ezetimibe on rates of cancer. Follow-up of longer duration will permit the balance of risks and benefits to be determined more reliably.

There you go. No perceived evidence of a cancer link. But for a more reliable balance of risks and benefits, studies of longer duration and using bigger sample sizes are suggested.