The Food and Drug Administration says Vytorin is safe enough, even though it doesn't work better than the statin Zocor, a much cheaper cholesterol-lowering medication. Last January the FDA raised fears that because of recent Vytorin studies, the agency might question the widely accepted idea that reducing LDL cholesterol lowers the chance of heart attack and stroke. Particularly worrisome was that more Vytorin patients in the studies died from such events than did patients taking Zocor, a statin drug. Now the FDA has updated its safety review of cholesterol-lowering drugs and "reaffirmed its position" that a high level of LDL is a cardiovascular risk factor, so lowering it is good.
Last January doctors were besieged by calls from worried patients taking Vytorin, a one-pill combination of Zocor and the nonstatin Zetia. A 720-patient study released by Vytorin's U.S. distributor, Merck/Schering-Plough, had shown that the drug worked no better than the same dose of Zocor alone at keeping fatty plaque from building up in the arteries of the neck (a pretty good stand-in for what's going on in the arteries of the heart). The following FAQ, posted when the original news hit and revised this week, offers useful guidance to those on Vytorin—and those who had been contemplating it.
What should I make of news reports about more deaths and heart attacks in patients using Vytorin? The number of such events was tiny and the differences meaningless, said the experts we consulted—two deaths compared with one and three nonfatal heart attacks compared with two. The study was far too small for any conclusions about heart events. Speaking of small studies, one that came out last August suggested a possible cancer risk posed by Vytorin. The following month, an analysis in the New England Journal of Medicine found no hard evidence of a link.
I don't need to stop taking Vytorin, then? No, said Roger Blumenthal, a Johns Hopkins cardiologist and chair of the American College of Cardiology's prevention committee. Besides the trivial number of cardiovascular problems, he said, there was no indication of liver-function problems, a sign of trouble.
Why was Vytorin supposed to work better than Zocor alone? In clinical trials that led to Vytorin's approval in 2004, the combined one-two punch of a statin, which inhibits cholesterol production in the liver, and Zetia, which keeps the substance from being absorbed in the intestine, knocked down the level of LDL cholesterol about 20 percent more than Zocor could by itself. That was the case in last January's study, too: the average LDL in the Vytorin group dropped by 58 percent compared with 41 percent in the Zocor group. Moreover, long-term studies of Zocor and the even more potent statin Lipitor have shown that radically lower LDL levels pay off in reduced cardiovascular events.
What was it that Vytorin failed to do? As fatty plaque builds up, it increases the thickness of the walls of the carotid arteries in the neck; progressive thickening is a good indicator of cardiovascular risk. Slowing or reversing the process demonstrates a drug's effectiveness. On average, the thickness in both groups increased (very slightly) during the two-year study.
W hat was Vytorin's problem? It remains mysterious. But the patients in the study weren't typical—all had extremely high LDL levels of above 300 because of a genetic condition. Whether the results of the study are relevant for individuals with more typical LDL isn't clear.
If I'm not taking Vytorin now , is there a reason I shouldn't start? Many experts feel that Vytorin shouldn't be anyone's first cholesterol-lowering drug. The clinical benefits and side effects of Zocor are well known, while Zetia—the nonstatin part of Vytorin—hasn't had time to amass a similar résumé. "We've always said you start with a statin and add on if a statin doesn't work well enough," said Mark Abramowicz, editor of the Medical Letter, an authoritative publication for physicians. Vytorin also remains an option for those on a high-dose statin who experience muscle or joint discomfort, weakness, or pain. The dose of Zocor in Vytorin can be as low as 10 milligrams, one eighth of the maximum.
Updated on 1/9/2009: This story has been updated to reflect developments that occurred in early 2009.