Medication Under a Microscope

Studies Raise Questions About Drugs' Efficacy Against Disease

A series of surprising findings about some of the most widely accepted assumptions in medicine has renewed debate about how aggressively doctors use drugs to prevent and treat some of the nation's leading health problems.

In addition to casting doubt on notions such as lowering cholesterol to prevent heart disease and normalizing blood sugar to protect diabetics, the studies involving well-known drugs such as Avandia and Vytorin have also rekindled concern about whether new medications are being tested adequately before being allowed on the market.

"We definitely need to pause and reassess our assumptions about what is best for patients," said Harlan M. Krumholz, a professor of medicine at Yale University. "Clearly we have more to learn."

No one is arguing that common strategies such as lowering cholesterol and blood sugar are unnecessary for many patients. But a number of researchers question whether too many Americans are being prescribed drugs, or combinations of drugs, including medications that have not been clearly shown to extend or improve life.

"There is a wake-up call in all of this," said Steven E. Nissen, a Cleveland Clinic cardiologist who often advises the government about new drugs. "We can't rely on assumptions. We don't always understand the biology of how drugs work as well as we think."

Others, however, warn against overreacting to a handful of studies, including some that are clearly preliminary. They argue that there is ample evidence to support current mainstream medical practice and that, if anything, too few patients are receiving recommended care.

"We have to be careful we don't get swept up by these swings and go too far one way or the other," said Sidney Smith, a professor of medicine at the University of North Carolina.

The first of the unexpected findings came in December 2006, when Pfizer abruptly terminated the development of a promising cholesterol drug. The drug, torcetrapib, was designed to cut the risk for heart disease by boosting "good" HDL cholesterol, a new strategy that was considered one of the most promising for fighting the nation's leading killer. But patients taking the compound in a large international study appeared to be at increased risk of dying.

About six months later, Nissen and his colleagues reported that the drug Avandia, which was widely used to lower diabetics' blood sugar levels, appeared to increase the risk of heart attacks.

Then, last month, Merck-Schering Plough Pharmaceuticals, a joint venture between the two companies, disclosed the results of a long-awaited study that suggested that its popular cholesterol-lowering drug Vytorin did not slow the progression of heart disease. That stirred uncertainty about whether driving cholesterol levels ever downward always helps and whether approving cholesterol-lowering drugs without showing that they reduce the risk for disease is appropriate.

Finally, 11 days ago, the National Institutes of Health announced that it was halting part of a major diabetes study after finding more deaths among patients who tried to push their blood sugar levels as close to normal as possible, raising more questions about whether lower is always better.

"I don't think you can leave these episodes and not shake your head and say, 'Wow, we really don't know as much as we think we do,' " Krumholz said.