Top 10 health stories of 2004

The promise and problems of tests and medications dominate the top 10 list. Merck’s withdrawal of Vioxx, a pain reliever, from the market and the 2004 flu vaccine shortage are cautionary tales. The systems for ensuring medication safety are porous. Safe, reliable supplies of vaccines are tenuous.

On the other side, if you’re curious about what 21st-century medicine holds in store, look at the research on genetic mutations that predict whether Iressa, the new lung cancer drug, will work. We’re entering an age in which genetic profiles will determine medical advice and treatment.

But the favorite item on the list is research suggesting that walking a couple of miles a day lowers the risk for dementia. How wonderful that something as complex as the human brain may benefit from something as simple as a regular stroll in the park! And you don’t need any sophisticated tests or drugs — just a pair of comfortable shoes.

1. Lowdown on cholesterol, high-dose statins. Revised government guidelines carved out a new “very-high-risk” category and set a super-low standard of 70 mg/dL or less for “bad” LDL cholesterol as a therapeutic option for that group. To reach LDL levels that low, most people would have to take a statin drug.

Meanwhile, a couple of major studies suggested that people who’ve had a heart attack or an episode of unstable angina might be able to prevent further problems by taking a statin, perhaps at a higher dose than usual. The PROVE-IT trial clearly showed the advantages of a daily 80-milligram dose of atorvastatin (Lipitor). The results of another study — involving simvastatin (Zocor) — were ambiguous, yet consistent with research showing protection from statins.

Statins lower LDL cholesterol. But some study results in 2004 suggest that it’s their antiinflammatory properties that make them effective as post–heart attack preventives. They seem to cool down the inflammation that leads to clogged arteries and the rupture of atherosclerotic plaques.

2. Cloning for stem cells. Two controversial research paths crossed in 2004 when South Korean scientists announced that they had created 30 cloned human embryos and harvested embryonic stem cells from one of them.

Dolly, the sheep cloned in 1996, proved the feasibility of creating an exact genetic copy of an adult mammal. But until the Korean effort, attempts to clone humans and monkeys had failed. Clones are created by scooping the nucleus — the “container” for genes in the center of a cell — from an egg and then inserting the nucleus of an adult cell in its place.

Embryonic stem cells could be the best hope for curing type 1 diabetes, Parkinson’s disease, and many other conditions. Some condemn embryonic stem cell research because it involves the destruction of human embryos.

Needless to say, cloning is controversial, too. But some experts say there is a clear distinction to be made between reproductive cloning — producing a clone with the goal of creating a child that has the genes of an adult — and therapeutic cloning — producing a clone for the sole purpose of harvesting stem cells.

If therapeutic cloning becomes acceptable and practical, the Koreans’ success may stand as one of the year’s major breakthroughs. Not only would therapeutic cloning be a ready source of embryonic stem cells, the stem cells would contain the patient’s own genes, reducing the risk that they would be rejected by the immune system.

3. The rise and fall of Vioxx. When the FDA approved rofecoxib (Vioxx) in 1999, some hailed it as a new “super aspirin” that relieved pain but wasn’t hard on the gut like other nonsteroidal anti-inflammatory drugs (NSAIDs). Global sales of Vioxx and celecoxib (Celebrex), another drug in the same class, were soon in the billions.

But in September 2004, Merck yanked its blockbuster off the market after a study showed that it doubled heart attack and stroke risk in people who took it longer than 18 months.

The news wasn’t a complete surprise: Soon after it came on the market, studies linked Vioxx with cardiovascular problems. Some experts say the FDA should have forced Merck to investigate these side effects much sooner.

This story has a couple of morals. First, multimillion-dollar ad campaigns are making many drugs much more popular than they’d ever be on purely medical grounds. Quite apart from its dangerous side effects, Vioxx was never shown to be a better pain reliever than run-of-the-mill NSAIDs like Advil. Even its main advantage, avoiding gastrointestinal problems, was oversold. Second, FDA approval is not a guarantee of safety — to say the least. Vioxx joins a growing list of FDA-approved medications (Baycol, Rezulin) that have been pulled from the market because of dangerous side effects.

4. Making smart drugs even smarter. The latest generation of cancer drugs zeroes in on abnormalities particular to tumor cells. These drugs — which include imatinib (Gleevec) and gefitinib (Iressa) — have been nicknamed “smart bombs” because they’re more selective than traditional cancer drugs, which attack all dividing cells. But problems remain. For example, Iressa, a last-resort lung cancer drug, only works in about 10% –20% of patients.

Harvard researchers may have found a way to make Iressa much “smarter.” They identified a genetic mutation in lung cancer cells that seems to predict whether Iressa will be effective. If the results hold up, tumor cells could be tested, and only people likely to respond to Iressa would be given the drug. These new drugs are expensive: Iressa costs about $1,700 a month, so having a genetic test instead of relying on trial and error could save a lot of money and spare some sick people treatment with a drug that won’t work for them. It’s an early example of pharmacogenomics — medications tailored to genetic makeup.

5. Bad news about drugs should see the light of day. Clinical trials are the gold standard of medical research, but are we only getting half the story from the thousands of trials conducted every year?

That question was on a lot of people’s minds in 2004 because of allegations that a British drug company, GlaxoSmithKline, hid findings that linked its popular antidepressant drug, paroxetine (Paxil), to suicidal thinking and behavior in children and adolescents.

The FDA subsequently put its strongest “black box” warning about this risk on labels for all the antidepressants in Paxil’s class, including fluoxetine (Prozac) and sertraline (Zoloft).

The proposed solution to selective reporting of results is a formal registry for all clinical trials. Before researchers started enrolling patients in a trial, they would be required to post a notice in a publicly accessible registry (regrettably, more than one may be established). In the opinion of some experts, this system would be effective only if registration was mandatory, policed (with penalties for noncompliance), and independent from the pharmaceutical industry.

6. Take your brain for a walk. Taking regular walks is not just one of the best ways to keep your body healthy; it may be good for your mind, too. Results from Harvard’s Nurses’ Health Study suggest that regular physical activity, including plain old walking, lowers the risk for cognitive impairment by 20% for women in their 70s. The Honolulu-Asia Aging Study — involving 2,300 “physically capable” men of Japanese ancestry between the ages of 71 and 93 — also issued walking papers. Participants who walked more than two miles daily were half as likely to develop dementia as those who walked less than a quarter of a mile per day.

It’s possible to confuse cause with effect here; perhaps cognitive decline makes people more sedentary, not vice versa. But the researchers made adjustments to take that possibility into account.

It makes sense that walking would keep us sharper. The brain, like other organs, benefits from a strong cardiovascular system that does a good job of supplying blood. Experiments also show that exercise may have direct neurological benefits, preserving brain cells and promoting the cell-to-cell communication needed for any mental activity.

7. PSA: Speed may matter. Judging by the declining mortality statistics for prostate cancer, most experts agree that PSA screening for the disease does more good than harm. Still, doctors worry that widespread use of this test results in too many biopsies and unnecessary treatment of small, slow-growing cancers.

A major study of men with normal PSA levels (4.0 nanograms or less per milliliter of blood) found the opposite problem: missed cancers. Of the 2,950 men enrolled in the study, 449 (15%) had prostate cancer — and 67 (2%) had serious, high-grade cancers.

So should we lower the threshold for a normal PSA? No, say some experts. They argue that lowering the threshold may find more cancers, but we still don’t have a surefire way of predicting which of those cancers will be aggressive and spread. The result could be more biopsies and surgery without offering patients a clear benefit.

In deciding whether to order a biopsy, there are other important factors to consider besides the PSA number, including family history. Another important question is how fast PSA levels have increased — often called “PSA velocity.” One study found that patients whose PSA levels had increased by more than 2.0 in the year before a diagnosis of prostate cancer had a much higher mortality rate than those with slower rates of increase.

8. Cost shifting to pay-tients. Each year since 2002, private health insurers have tried to rein in double-digit premium increases by shifting costs to their customers. One way they do it is by increasing copayments for doctor and hospital visits. Many insurers have tiered their drug coverage: low copayments for generic drugs, more for brand-name medications on a “preferred” list (a formulary), and much more for brand-name drugs that aren’t on the formulary.

Some companies are applying the same approach to hospital care. If you have an operation at an expensive academic medical center instead of a less-expensive community hospital, your copayment will be higher.

These changes may be having the intended effect. Because people are “seeing” more of the cost, they may become better shoppers, weighing cost against benefit for themselves. For example, although spending on prescription drugs is still going up, the rate of increase peaked in 1999. Some health economists credit greater use of generics driven by tiered drug coverage. However, many say that in the long run, cost shifting will make only a minor dent in health care spending because the biggest expense lies in the treatment of serious illnesses, which involves less discretionary spending.

9. Controversy over coronary calcium scanning. After former President Clinton needed emergency bypass surgery, many Americans worried whether they, too, might have undetected arterial clogging. Scanning coronary arteries for signs of calcium is a high-tech way to uncover the problem early; calcium buildup is a feature of the atherosclerotic process that leads to heart attacks. The scans are quick and painless, but expensive ($250–$400).

Skeptics say, though, that this may be an example of the type of test that adds more cost than benefit. Even people with minimal atherosclerosis (and almost all Americans have some) may have a “positive” scan that leads to unnecessary further tests and even treatment.

After a press report said the American Heart Association was getting ready to endorse the scans, the organization decided against publishing a new statement and reemphasized the position it took in 2000: The scans are best used as tie-breakers when some other criteria (cholesterol levels, family history, etc.) indicate increased risk and others do not. A positive scan might tip the balance toward treatment.

10. The flu vaccine shortage. The 2004 flu vaccine shortage shows that the American system for immunizing people may be a disaster waiting to happen. Part of the problem is economic: Companies have fled the vaccine business because it’s not a big moneymaker. Some have suggested that the government take over vaccine manufacturing. More realistic are proposals to realign economic incentives to lure companies back into vaccine manufacturing.

Technological innovation would also help. The bulk of flu vaccine is made with a 50-year-old system that depends on chicken eggs and educated guesses about which strains of the virus will circulate each winter. FluMist, the nasal spray vaccine, is a step in the right direction but it uses a live, although weakened, virus and is only approved for healthy people between the ages of 5 and 49. Some experts say our best hope is a genetically engineered vaccine that could be quickly altered to match whatever flu strains are in circulation.