It can take scientists a decade or more to determine whether a drug actually works. In the meantime, doctors rely on other measures, like testing blood pressure and cholesterol levels, to determine whether a drug is having positive effects. But recent studies challenge the practice of prescribing medicine based on certain test results.
Doctors call it "treating the numbers" — trying to get a patient's test results to a certain target, which they assume will treat — or prevent — disease. But earlier this year, a study on a widely used cholesterol drug challenged that assumption.
Vytorin, a combination of two cholesterol-lowering agents, certainly lowers cholesterol. But patients taking it didn't have any less plaque in a major artery than those taking a less-potent drug.
When the results came out, Dr. Steve Atlas of Massachusetts General Hospital began getting calls from his patients — and his mom.
"For my first patient, it was like let's make a visit and schedule an appointment. For my mother, it became a longer discussion," Atlas says.
Ellen Atlas is a tennis-playing 75-year-old who has been taking Zetia — one of the cholesterol-lowering ingredients in Vytorin — because regular statin drugs caused muscle pain, a common side effect. Zetia reduced her cholesterol very nicely. But she wanted to know whether it was doing her any good.
"For my mom, it was like, wow! I'm treating the number and I'm not going to necessarily prevent the stroke that her mother had? All of a sudden, it was like, 'I don't want to take this medicine!' "
Steve Atlas was brought up short by the surprising cholesterol results.
"It's a big deal because it reminds us of something that we often forget: the number isn't the outcome. And this raises concerns that just lowering the number doesn't get you where you want to be," he says.
Dr. Ned Calonge, chairman of a national task force that assesses what works and what doesn't in preventive medicine, says he still believes that cholesterol-lowering drugs reduce heart disease. But he says the recent study challenges the goal of getting Americans' cholesterol lower and lower.
"Now, what's open is — is lower better? And I think a lot of people believed it would be, and there are many of us that were saying, 'You're going to need to show me,' " he says.
Lately, studies have also challenged other cherished assumptions — like lowering blood sugar. For a long time, doctors have believed that getting diabetic patients' blood sugar as close to normal as possible would prevent heart attacks. A drug called Avandia lowers blood sugar very well.
It was approved in 1999 and was heralded as "one of the newer and greater drugs for the treatment of diabetes," says Dr. Cliff Rosen. Rosen is the chairman of a Food and Drug Administration advisory panel that concluded unanimously last year that patients taking Avandia actually had more heart attacks and strokes.
Rosen says the Avandia story is a caution against treating millions of patients on unproven assumptions.
Normalizing blood sugar probably does prevent heart disease for patients with Type 1 diabetes. But it's unproven for the far more common Type 2.
"It's not clear yet — even now, even after all these years — that in Type 2 diabetes, keeping your blood sugar at a certain point will prevent heart disease," Rosen says.
In fact, last month a federal study showed that a big group of Type 2 diabetics who got aggressive treatment to lower blood sugar actually had more deaths than those on standard therapy.
The treating-the-numbers problem also comes up in decisions to use common tests. One is bone-density scans for osteoporosis. Rosen, a bone disease specialist, often tries to talk patients out of getting the $400 scans to check whether their drugs are working.
"These are good drugs. They work in osteoporosis. But they work not just because they change bone density. That's the bottom line. And you know what? I've been zero percent successful — I have never yet talked an individual out of a bone-density follow-up measurement," Rosen says.
On the other hand, Atlas, the Boston internist, says many of his patients are choosing not to take cholesterol-lowering drugs as a result of the recent study.
But he's uncomfortable letting his own mother's elevated cholesterol go untreated.
Ellen Atlas has stopped taking Zetia. She has improved her diet and increased her exercise. But her son is skeptical that that'll be enough.
During a phone call, Steve Atlas tells his mother, "I obviously hope that your numbers are better with the lifestyle changes that you've been making, because that'd be great. But if they're still high, then starting sort of like a baby dose, a really low dose ..."
Mother and son hope a low dose of a tried-and-true statin will get her close to the right cholesterol number — without the side effects she suffered before.