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Failed Vytorin Study Raises Questions About Cholesterol

Posted by medconsumers on February 1, 2008

A firestorm of bad publicity erupted over cholesterol drugs last month when an expensive combination drug proved to be no better than an older drug alone. This finding was suppressed for 20 months by Merck and Schering-Plough, the two companies that make Vytorin, which is a one-pill combination of Zetia and Zocor. Their two-year trial failed to prove that Vytorin is better than Zocor alone for slowing plaque accumulation; instead atherosclerosis worsened in those taking Vytorin.

But the study results were not revealed until the two drug companies were pressured into doing so by an article in The New York Times and a Congressional inquiry. Worldwide, about one million prescriptions for Vytorin and Zetia are written each week, and they generated about $5 billion in sales last year. Zocor can be purchased under its generic name simvastatin for less than $6 for a month’s supply; whereas an equivalent amount of Vytorin costs about $100. It was obviously in the two companies’ interest to withhold the negative results for as long as they could get away with it.

When Vytorin came on the market two years ago, it was impossible not to be cynical about its purpose. Merck’s patent for Zocor was running out, and its blockbuster status would soon be diminished with generic competition. The company joined forces with Schering-Plough, maker of Zetia, and sought FDA approval for Vytorin. Their FDA-required trials showed a 17% greater reduction in LDL, the so-called bad cholesterol, than Zocor alone.

Making this 17% reduction in LDL look like an amazing achievement was not much of a stretch. Merck and the makers of other statin drugs like Lipitor and Pravachol had already paved the way. Their respective marketing machines had long ago misled most of us (doctors included) into thinking that cholesterol reductions equal heart attack reductions. One consistently overlooked fact about statins: They are far better at lowering cholesterol than preventing heart attacks or strokes. And those small reductions in heart attacks and strokes shown in clinical trials are largely confined to high-risk middle-aged men and those with heart disease or diabetes. Vytorin, on the other hand, has not been proven to reduce heart attacks or strokes in anyone.

LDL Reduction Irrelevant

Though doctors tend to focus their statin-taking patients on the size of their LDL reductions, heart disease researchers have long ago noted that this is likely irrelevant. Statin trials often show that the size of the cholesterol reductions are not consistent with reductions in heart attacks. Such observations led researchers to suspect that the ability of statins to reduce heart attacks and strokes has less to do with cholesterol reduction and more to do with other biological effects like plaque stability and anti-inflammatory effects. Another important but overlooked observation: “Elevated LDL identify less than one half of individuals who will die from coronary heart disease” (Rosenson et al. Antithrombotic Properties of Statins, JAMA, May 27, 1998).

The fall-out from the Vytorin debacle continues to reverberate. At this writing, Merck and Schering-Plough are running full-page ads daily in the Times and Wall Street Journal, warning people not to be confused by a single study and to continue taking Vytorin. The advice was backed by the American Heart Association, which appeared to be an independent source until The Times reported that the AHA receives nearly $2 million a year from Merck/Schering-Plough Pharmaceuticals.

One of the unintended consequences of two drug companies withholding their negative trial results is that it led some in the media, notably Alex Berenson, an investigative reporter for the Times, to look back at another important failed cholesterol drug trial and question the very foundation of heart disease prevention. In his heretically titled article “Cholesterol as a Danger Has Skeptics,” Berenson cites Pfizer’s trial of its much-anticipated drug torcetrapib that raised HDL, the good cholesterol, and lowered LDL. The trial had to be stopped in 2006 because the drug caused heart attacks and strokes. (Sound familiar? Postmenopausal hormones were widely prescribed because they were so good at improving cholesterol levels but they also increased the risk of heart attack, stroke and blood clots.) “Torcetrapib’s failure shows that lowering cholesterol does not prove a drug will benefit patients,” said a skeptical Walter Reed cardiologist quoted in Berenson’s article.

Many researchers, physicians and scientists around the world have long questioned the import of high cholesterol for anyone other than middle-aged men. In fact there is an International Network of Cholesterol Skeptics (disclosure: we belong), but the skeptics have been marginalized over the years. Now some mainstream media like Business Week and the cardiology Web site, are willing to give them voice.

Could the house of cards be falling? Would the house of cards be allowed to fall when a worldwide $40 billion-a-year industry is at stake?

For More Information

The International Network of Cholesterol Skeptics

Business Week magazine ( click into past issues, January 17, 2008 Lipitor cover story: “Do Cholesterol Drugs do any Good?” from Web MD, see video blog of Eric J. Topol, MD, who questions the import of LDL reduction in “Temple of the LDL Cholesterol.”

Maryann Napoli, Center for Medical Consumers ©
February 2008

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