Study touches off cholesterol debate

Merck and Schering-Plough are running full page ads, as in the Wall Street Journal, in an attempt to control the damage from a study questioning the benefits of ezetimibe (Zetia) or Vytorin (ezetimibe/simvastatin). “All of us at Merck and Schering-Plough proudly stand behind the established efficacy and safety profiles of ZETIA and VYTORIN,” states the advertisement. But it also notes that “ZETIA [a drug that limits cholesterol absorption] has not been shown to prevent heart disease or heart attacks.”

Two years after the “Enhance” study ended, results have not been published in a medical journal, but will be presented at a cardiology conference in March. Findings were issued in a press release, after Congress had pressured the companies to disclose the outcome. The delay is related to complexity, not to the negative nature of the findings, spokesmen said (Alex Berenson, New York Times 1/15/08).

The combination drug was shown to lower LDL cholesterol more than either ezetimibe or simvastatin (Zocor) alone; however, arterial plaque formation was not reduced. Actually, plaques grew twice as fast in patients on Vytorin, but the difference was not statistically significant (Tara Parker-Pope, New York Times 1/22/08).

The results were called “shocking” by Dr. Steven Nissen, chairman of cardiology at the Cleveland Clinic. But at least “it didn’t show any harm,” stated Dr. Paul D. Thompson, director of cardiology at Hartford Hospital.

About 5 million patients are taking Zetia or Vytorin worldwide, and the $5 billion in sales are important contributors to the drug companies’ profits.

At the same time, CBS News and Business Week are discussing whether statins and cholesterol are over-hyped (CBSNews.com 1/17/08).

Business Week points out that the touted 36% reduction in heart-attack risk is a relative number. The absolute risk is reduced by 1%, from 3 in 100 to 2 in 100. And while benefits are overstated, risks are understated. BW states that side effects occur in 10% to 15%, not the mere 2% to 3% claimed by statin-drug advocates.

Some assert that the benefits of statin drugs result from their vitamin D-like actions, and that vitamin D supplements provide the benefit without the risks (Bill Sardi, LewRockwell.com). A meta-analysis of randomized trials of patients receiving vitamin D supplementation showed a 0.93 relative risk for all-cause mortality (Philippe Autier and Sara Gandini, Arch Intern Med 2007;167:1730-1737). The mechanism may be prevention of arterial calcification.

Additional information: