Harvard Health Letters

Bayer first started selling aspirin as a pain and fever reliever over 100 years ago. Now we've got a slew of other choices, including over-the-counter drugs like acetaminophen (Tylenol), ibuprofen (Advil, Motrin, other brands), and naproxen (Aleve), so aspirin for pain relief seems out of date. Children don't grow up taking aspirin like they used to, because it's been linked to Reye's syndrome, a rare but potentially fatal childhood condition that involves swelling of the liver and brain. And there's no doubt aspirin can be hard on the stomach; it can lead to ulcers if taken often.

Even so, its value as a pain reliever is underestimated these days, and in many cases aspirin could be used instead of medications that are more expensive, more heavily marketed, and often both. For example, there was a report in April 2010 that fairly large doses (900 to 1,000 milligrams) of aspirin are just as effective at stopping migraine attacks as sumatriptan (Imitrex), the popular brand-name migraine drug.

A SECOND CAREER

Plenty of people are still taking aspirin -- 50 million Americans by one count -- because it has enjoyed a remarkable second career in cardiovascular prevention. There's wide agreement that if you have had a heart attack or stroke, taking low doses of aspirin on a regular basis (daily or every other day) will reduce the likelihood of having another one.

Research has also shown that a low-dose aspirin habit reduces the risk of a first-time heart attack or stroke, although the way the risk-benefit math works out, only people who have a number of risk factors for cardiovascular disease are advised to take aspirin.

Now researchers are trying to figure out if aspirin might also have a protective effect against cancer. Some of the most promising results have been for colon cancer and the polyps that typically precede it.

The problem is that randomized trials, which usually carry more weight than epidemiologic findings, haven't been so encouraging. The Women's Health Study, sponsored by the National Institutes of Health, included about 40,000 American women, ages 45 and older, who were randomly assigned to take either 100 milligrams of aspirin or a placebo every other day for 10 years.

Results from the study, reported in 2005, didn't show aspirin as having any effect on any cancer. The Harvard-based Physicians' Health Study -- best known for showing that aspirin has protective effects against heart attacks -- also came up empty-handed when its data were analyzed for protection against colon cancer.

One explanation for the mixed results is that the dose of aspirin used in the randomized studies, while adequate for cardiac prevention, might be too small for colon cancer purposes. Data from the epidemiologic studies and other research suggests that higher doses of aspirin (perhaps 325 mg a day, or even more) may be needed before colon cancer prevention kicks in. But doses that high also increase the risk of serious side effects, like hemorrhagic stroke, so the benefits have to be weighed carefully against the risks.

Some experts are reserving judgment. In 2009, a group who met at the International Conference on Cancer Prevention in Switzerland was supposed to issue a consensus statement on aspirin and cancer prevention. Instead, they chose to identify areas that need further study.

Aspirin inhibits the cyclooxygenase (COX) enzymes, which come in two forms, COX-1 and COX-2. The COX enzymes play a crucial role in several "pathways," the cascades of biochemical events that determine how our bodies function. By inhibiting COX-1, aspirin winds up making platelets less "sticky," so blood is less likely to clot, which makes a heart attack or stroke less likely. COX-1 also produces hormone-like molecules called prostaglandins that protect the stomach, so, by interfering with COX-1, aspirin also makes the stomach lining more vulnerable to ulcers.

COX-2 stirs up fever and inflammation; by inhibiting COX-2, aspirin helps put out those fires. Inhibition of COX-2 may also explain aspirin's anti-cancer effects, although cancer exploits multiple pathways, which is one of the many reasons it's so difficult to prevent and treat.

[See 14 Things You Might Not Know About Aspirin

A NEW TWIST

In March 2010, Harvard researchers added another twist to the aspirin tale when they reported results suggesting that if aspirin does possess cancer-fighting properties, they might be most evident among cancer survivors.

Their study included about 4,000 women in the Nurses' Health Study who'd been diagnosed with breast cancer over a 26-year period and who had supplied researchers with information about their use of aspirin. The Harvard researchers found that the breast cancer survivors who had taken aspirin regularly after being diagnosed with the disease were 70 percent less likely to have died from the breast cancer. Regular use was defined as taking aspirin two to five days a week.

So where does this leave us? With aspirin as a fine but unfashionable reliever of pain and fever, a strong defender against heart disease and stroke, but a bit iffy as a preventer of cancer. - Harvard Health Letter

 

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