For the second time in six months, ezetimibe (Zetia), a featherweight LDL (bad) cholesterol fighter, has taken a hit, and this blow could well end its career. The referee, with the initials FDA emblazoned on his white lab coat, has begun the countdown.
Ezetimibe (made by Schering-Plough and still on patent as the brand name Zetia) was approved in 2002 for use with a statin to achieve additional small reductions in LDL cholesterol, compared to just the statin alone. In 2004, when Merck's brand of simvastatin, known as Zocor, was about to go off patent, Merck teamed up with Schering-Plough to produce a new patented product called Vytorin, a combination of simvastatin and Zetia. A vigorous advertising campaign resulted in billions of dollars in sales.
Then, in February of this year, the first blow landed: A two-year study showed that the combination product was no better than simvastatin alone in decreasing the growth rate of plaque in the carotid arteries. At that time the Consumer Reports Health blog referred to ezetimibe, alone or in combination, as "excess and expensive baggage, to be put back on the shelf and be used only in people who were either intolerant of statins or in conjunction with a generic statin only when LDL cholesterol goals were difficult to achieve."
The second, and much more devastating, punch was landed in early September when The New England Journal of Medicine reported the preliminary results of a study that pitted Vytorin against a placebo to compare the number of strokes and heart attacks that occurred in older people with narrowing of the heart’s aortic valve. After five years, except for a decreased number of coronary artery bypasses in the Vytorin group, there were no differences in the incidence of strokes and heart attacks.
What did show up, however, was an increased number (101 vs. 65) of cancer cases and deaths (37 vs. 20) from cancer. Also analyzed in that issue of the Journal were two other similar ongoing studies in England. According to those studies, looked at after just two years, that increased cancer incidence could not be confirmed. [The FDA also reported that their analysis of the available interim data from the two ongoing English studies of Vytorin, showed no increased incidence of cancer.] But a statistically non-significant trend toward increased cancer deaths (97 vs. 72) was noted.
The final results of the English studies will not be known until 2012. The U.S. Food and Drug Administration is studying the situation and is expected to make an announcement in six months.
As with the Avandia caper, health professionals and their patients are faced with a conundrum. The issues now are not ezetimibe's relatively limited ability to reduce LDL cholesterol or its cost, but its safety. Good scientists are on either side of the question: Is the evidence sufficient to indict? Consumer Reports believes that whenever safety is an issue with a drug, caution has to be brought to bear until more definitive studies are done. Our previous cautions about Zetia, and its use in the combination product Vytorin, can now be extended to exclude its use in new patients, especially those with a personal history of cancer. The reasons for maintaining patients on Zetia or Vytorin should be carefully examined and its use limited to those with multiple coronary risk factors who cannot tolerate statins.
Ezetimibe is down, a recipient of the one-two punch, and the referee has begun his slow count: one, two, three …
CR’s Recommendation: Vytorin or Zetia should not be prescribed for new patients, particularly those with a personal history of cancer. Patients currently taking Vytorin or Zetia should be reevaluated to make sure the potential benefits outweigh the potential risks. Under no circumstances should a patient discontinue any medication on his or her own volition without discussing the matter with a physician.
—Marvin M. Lipman, M.D., chief medical adviser
Find out if statins, fibrates, and the Mediterranean diet (subscribers only) could help lower your cholesterol, and take a look at our free Best Buy Drugs report on low-cost cholesterol-lowering drugs.