The news keeps getting worse for two heavily promoted cholesterol drugs, Vytorin and Zetia. These drugs were supposed to offer a valuable alternative to the older cholesterol-lowering agents known as statins, a class that includes Lipitor, Zocor and other drugs that not only reduce cholesterol but also reduce the risk of heart attacks. In clinical trial results released this week, the newer drugs failed to reach their main goal: slowing the growth of artery-clogging plaques — a suggestion that they might not help ward off heart attacks.
It is distressingly late to be learning that these drugs may provide little or no benefit. They were approved on the basis of evidence that they reduce the level of so-called bad cholesterol in the blood. That data was taken as presumptive evidence that the drugs would reduce heart-attack risks. Despite this slim supporting data, vigorous promotion propelled them to combined sales of more than $5 billion last year, placing them among the world’s top-selling drugs.
An analysis in the New England Journal of Medicine found that the drugs captured 15.2 percent of the cholesterol-lowering market in this country, driven by an advertising campaign aimed at consumers and aggressive marketing to doctors. But they claimed only 3.4 percent of the market in Canada, where advertising to consumers is prohibited, Vytorin is unavailable and public programs restrict usage. These are drugs that became blockbusters thanks to marketing muscle, not scientific proof of effectiveness.
There are also justifiable concerns that Merck and Schering-Plough, the companies that make the drugs, may have sat on adverse data for more than a year lest their sales be undermined. In e-mail messages unearthed by Senate investigators, the lead scientist on the study warned that repeated delays in releasing the results made it look as if the company was trying to hide something.
In the clinical trial, 720 European patients with genes that cause abnormally high cholesterol levels were given either Vytorin, a combination pill that contains both Zetia and Zocor, or simply Zocor alone. As expected, the combination pill proved better than the statin alone at reducing the level of bad cholesterol. But to everyone’s surprise, Vytorin failed to slow the growth of fatty plaques in the arteries, and it may have even allowed greater growth than the statin did.
Vytorin and Zetia are clearly down, but not necessarily out. It remains possible, for example, that the reason Vytorin had little effect in reducing plaque was that most of these patients had been taking statins for years and their plaque had already been depleted to the point that Vytorin had little room to improve the situation. It is also possible, however, that Vytorin and Zetia are simply less effective than the statins. Other trials now under way may clarify Vytorin’s value in coming years. Meanwhile, heart experts are surely right that Vytorin and Zetia should be a last resort for patients who can’t get their cholesterol down any other way.
