Washington DC - Following the recent findings from ACCORD and ENHANCE, the questions of whether too many drugs are being used to treat cardiovascular disease and diabetes and whether new drugs are being adequately tested before being allowed on the market are addressed in an article in the February 19, 2008 issue of the Washington Post.

Journalist Rob Stein quotes Dr Harlan Krumholz (Yale University, New Haven, CT) as saying: "We definitely need to pause and reassess our assumptions about what is best for patients. . . . Clearly we have more to learn," while Dr Steven Nissen (Cleveland Clinic, OH) is reported as saying: "There is a wake-up call in all of this. . . . We can't rely on assumptions. We don't always understand the biology of how drugs work as well as we think."

But Dr Sidney Smith (University of North Carolina, Chapel Hill) warns against overreacting to a handful of studies and says 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," he says in the article.

Stein outlines the three latest studies to throw into question the idea of using surrogate end points to evaluate drugs—the failure of torcetrapib, which raised HDL cholesterol but also increased mortality; the ENHANCE study, showing no reduction in atherosclerosis progression with ezetimibe despite its LDL lowering; and the shock results of ACCORD, in which a very intensive strategy to lower blood-sugar levels in diabetics was associated with increased mortality. "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 is reported as saying. Dr Nortin Hadler (University of North Carolina) adds: "There are a lot of things we do in this country where we treat these surrogate measures with very little evidence that we are actually treating the patient."

Nissen suggests in the article that drugs could be approved on the basis of surrogate end points but only with the proviso that a clinical-outcome trial is conducted. But the FDA is defending the approval of drugs based on surrogate end points. Robert Temple (FDA's Center for Drug Evaluation and Research) told the newspaper: "Some people don't respond adequately to available therapy. . . . You have to make a judgment about whether you want to have a way of treating that now or you want to wait five years, 10 years, who knows? That's a judgment that has to be made."

Others lay the blame with the drug companies. Dr John Abramson (Harvard Medical School, Boston, MA), who is author of the book Overdosed America, comments: "What's going on here is our research enterprise is almost completely controlled by the pharmaceutical industry. . . . It's their job to create a need for their products. Their job is not to maximize public health." Dr Howard Brody (University of Texas Medical Branch at Galveston) adds: "People are making a ton of money by selling the drugs and the monitoring equipment. . . . It distracts our patients from what really matters more, which may be getting more exercise or making lifestyle changes that ultimately may be more beneficial than obsessing about their blood sugar or playing with their little monitor device."

And some believe doctors themselves add to the problem by overprescribing drugs. Dr Mark Ebell (deputy editor of American Family Physician) is quoted as saying: "It feeds on the American psyche of 'Just don't stand there, do something.' . . . We want to do everything possible. Sometimes pushing too hard to make a number look better can have unexpected collateral effects that do harm a patient."

But the Post also reports lipid expert Dr Scott Grundy (University of Texas Southwestern Medical Center, Dallas) as saying that the link between cholesterol and heart disease is "the most established fact in all of medicine . . . the more you lower LDL cholesterol, the more you lower the risk." But Grundy adds: "Drugs can be great, but they can have side effects. . . . If you start piling on one drug after another, you can get into trouble."