Do Cholesterol Drugs Do Any Good?

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For one thing, many researchers harbor doubts about the need to drive down cholesterol levels in the first place. Those doubts were strengthened on Jan. 14, when Merck and Schering-Plough (SGP) revealed results of a trial in which one popular cholesterol-lowering drug, a statin, was fortified by another, Zetia, which operates by a different mechanism. The combination did succeed in forcing down patients' cholesterol further than with just the statin alone. But even with two years of treatment, the further reductions brought no health benefit.

DOING THE MATH

The second crucial point is hiding in plain sight in Pfizer's own Lipitor newspaper ad. The dramatic 36% figure has an asterisk. Read the smaller type. It says: "That means in a large clinical study, 3% of patients taking a sugar pill or placebo had a heart attack compared to 2% of patients taking Lipitor."

Now do some simple math. The numbers in that sentence mean that for every 100 people in the trial, which lasted 3 1/3 years, three people on placebos and two people on Lipitor had heart attacks. The difference credited to the drug? One fewer heart attack per 100 people. So to spare one person a heart attack, 100 people had to take Lipitor for more than three years. The other 99 got no measurable benefit. Or to put it in terms of a little-known but useful statistic, the number needed to treat (or NNT) for one person to benefit is 100.

Compare that with, say, today's standard antibiotic therapy to eradicate ulcer-causing H. pylori stomach bacteria. The NNT is 1.1. Give the drugs to 11 people, and 10 will be cured.

A low NNT is the sort of effective response many patients expect from the drugs they take. When Wright and others explain to patients without prior heart disease that only 1 in 100 is likely to benefit from taking statins for years, most are astonished. Many, like Winn, choose to opt out.

Plus, there are reasons to believe the overall benefit for many patients is even less than what the NNT score of 100 suggests. That NNT was determined in an industry-sponsored trial using carefully selected patients with multiple risk factors, which include high blood pressure or smoking. In contrast, the only large clinical trial funded by the government, rather than companies, found no statistically significant benefit at all. And because clinical trials themselves suffer from potential biases, results claiming small benefits are always uncertain, says Dr. Nortin M. Hadler, professor of medicine at the University of North Carolina at Chapel Hill and a longtime drug industry critic. "Anything over an NNT of 50 is worse than a lottery ticket; there may be no winners," he argues. Several recent scientific papers peg the NNT for statins at 250 and up for lower-risk patients, even if they take it for five years or more. "What if you put 250 people in a room and told them they would each pay $1,000 a year for a drug they would have to take every day, that many would get diarrhea and muscle pain, and that 249 would have no benefit? And that they could do just as well by exercising? How many would take that?" asks drug industry critic Dr. Jerome R. Hoffman, professor of clinical medicine at the University of California at Los Angeles.

Drug companies and other statin proponents readily concede that the number needed to treat is high. "As you calculated, the NNT does come out to about 100 for this study," said Pfizer representatives in a written response to questions. But statin promoters have several counterarguments. First, they insist that a high NNT doesn't always mean a drug shouldn't be widely used. After all, if millions of people are taking statins, even the small benefit represented by an NNT over 100 would mean thousands of heart attacks are prevented.

That's a legitimate point, and it raises a tough question about health policy. How much should we spend on preventative steps, such as the use of statins or screening for prostate cancer, that end up benefiting only a small percentage of people? "It's all about whether we think the population is what matters, in which case we should all be on statins, or the individual, in which case we should not be," says Dr. Peter Trewby, consultant physician at Darlington Memorial Hospital in Britain. "What is of great value to the population can be of little benefit to the individual." Think about buying a raffle ticket for a community charity. It's for a good cause, but you are unlikely to win the prize.