Do Cholesterol Drugs Do Any Good?

What would work better? Perhaps urging people to switch to a Mediterranean diet or simply to eat more fish. In several studies, both lifestyle changes brought greater declines in heart attacks than statins, though the trials were too small to be completely persuasive. Being physically fit is also important. "The things that really work are lifestyle, exercise, diet, and weight reduction," says UCLA's Hoffman. "They still have a big NNT, but the cost is much less than drugs and they have benefits for quality of life."

Difficult risk-benefit questions surround most drugs, not just statins. One dirty little secret of modern medicine is that many drugs work only in a minority of people. "There's a tendency to assume drugs work really well, but people would be surprised by the actual magnitude of the benefits," says Dr. Steven Woloshin, associate professor of medicine at Dartmouth Medical School.

A good example: Beta-blockers are seen as essential in treating congestive heart failure. Yet studies show that an average of 24 people must take the drugs for seven months to prevent one hospitalization from heart failure (thus, an NNT of 24). And 40 people must take it to prevent one death (NNT of 40). "Even for medications we consider effective, we see NNTs in the 20s or higher," says Dr. Henry C. Barry, associate professor of family medicine at Michigan State University College of Human Medicine.

For many other drugs, the NNTs are large. Take Avandia, GlaxoSmithKline's drug for preventing the deadly progression of diabetes. The blockbuster, with $2.6 billion in U.S. sales in 2006, made headlines in 2007 when an analysis of clinical trial data showed it increased the risk of heart attacks. The largely untold story: There's little evidence the drug actually helps patients. Yes, Avandia is very good at lowering blood sugar, just as statins lower cholesterol levels. But that doesn't translate into preventing the dire consequences of diabetes, including heart disease, strokes, and kidney failure. Clinical trials "failed to find a significant reduction in cardiovascular events even with excellent glucose control," wrote Dr. Clifford J. Rosen, chair of the Food & Drug Administration committee that evaluated Avandia, in a recent commentary in The New England Journal of Medicine. "Avandia is almost the poster child for everything wrong with our system," says UCLA's Hoffman. "Its NNT is close to infinite."

Regarding Avandia, Dr. Murray Stewart, Glaxo's vice-president for clinical development, says that the evidence of its benefits against heart disease and other major complications of diabetes "is still inconclusive." But the drug has other benefits, he argues, such as delaying the need to take insulin.

When other medications widely believed to be effective were put to the test of a clinical trial, they flunked. Hormone replacement therapy didn't protect against heart disease. Anti-psychotic drugs were actually less effective than a placebo in reducing aggression in patients with intellectual disability.

The truth about drugs' effectiveness wouldn't be as worrisome if consumers and doctors had an accurate picture of the state of knowledge and could make rational decisions about treatments. Studies by Darlington Hospital's Trewby, UBC's Wright, and others, however, show that patients expect far more than what the drugs actually deliver.

Why the mismatch? Some of the blame goes to the way results are presented. A 36% decline in heart attacks sounds more dramatic and important than an NNT of 100. "It comes as a shock to see the NNT," says Dr. Barnett S. Kramer, director of the office of medical applications of research at the National Institutes of Health. Drug companies take full advantage of this; they advertise the big percentage drops in, say, heart attacks, while obscuring the NNT. But when it comes to side effects, they flip-flop the message, dismissing concerns by saying only 1 in 100 people suffers a side effect, even if that represents a 50% increase. "Many physicians don't know the NNT," says Dr. Darshak Sanghavi, a pediatric cardiologist and assistant professor of pediatrics at the University of Massachusetts Medical School and a fan of using NNTs.