|Take two: Aspirin
New uses and new dangers are still being discovered as aspirin enters its second century.
As any good son would, Felix Hoffmann hated to see his father suffering from arthritis and the severe side effects of the sodium salicylate used to treat it. But unlike most sons, Hoffmann had the means to help. A chemist at the Farbenfabriken Friedrich Bayer in Germany, Hoffmann began tinkering with salicylic acid in hopes of preserving its inflammation-fighting properties while easing its harsh effects on the stomach. The result, in 1897, was acetylsalicylic acid, which Bayer began marketing in 1899 under the trade name Aspirin.
In the century since, a throng of other nonsteroidal anti-inflammatory drugs (NSAIDs) has emerged. Even so, aspirin has become the most widely consumed drug in the world, with Americans gulping down 29 billion pills a year.
Many of these billions are taken to ward off heart and artery disease. The FDA has approved the use of aspirin (1) to reduce the risk of
New century, new uses
Cancer. Aspirin looks especially promising for preventing certain cancers. In 1983, researchers published case studies of four people whose gastrointestinal polyps regressed when they were put on the NSAID Sulindac (2). Since then, scientists have explored whether NSAIDs can reduce the odds of suffering from cancer. Researchers have found increased levels of the enzyme cyclooxygenase-2 (COX-2) in some tumors, and aspirins ability to inhibit this enzyme might help suppress tumors.
Experiments show that some NSAIDs, including aspirin, inhibit various cancers in rats and mice. In several studies in which people with and without colorectal cancer were queried about their medical history, the risk of colon cancer was much lower in those who were regular NSAID users. Other studies started with NSAID users and nonusers and followed them to see which cancers they got. Most found lower rates of colorectal cancer in the NSAID users. These studies suggest that regular NSAID use cuts colorectal cancer risk by 4050%. If these results are confirmed, aspirin and other NSAIDs may have a role as cancer preventives for people at high risk for colon cancer (3).
Heart. Aspirin may have additional cardiovascular uses. In the U.S. Physicians Health Study (as reviewed in 1, 35), aspirin use reduced first heart attacks by 44% among healthy men. But before advocating widespread use, trials are needed to determine the relative benefits and risks of this use for the general public.
Stroke. Research to determine whether aspirin can prevent not just a second but also a first stroke is further along. Evidence suggests that aspirin may help some people at high risk for strokes. Studies show that aspirin reduces the risk of first strokes in people who have atrial fibrillation, a disturbance in heart rhythm that quintuples the risk of ischemic stroke (6). But the Physicians Health Study, studying mostly low-risk subjects, found that aspirin did not lower the risk of stroke and may have actually raised it (as reviewed in 3, 7).
Other. Studying patients who had suffered hip fractures or had undergone hip or knee replacement surgery, some of whom had taken aspirin for five weeks, the Pulmonary Embolism Prevention trial found another benefit. Researchers found that for aspirin-receiving patients, the risk of developing pulmonary embolism (an artery blockage in the lung) and deep-vein thrombosis (a clot in a deep vein) was reduced by more than one-third compared with subjects taking a placebo (8).
Mixed results have plagued research on other potential uses. There is evidence for and against aspirins ability to prevent cataracts, preeclampsia (a pregnancy complication), and dementia. Also, various small studies suggest sundry other uses, from treating gum disease to preventing osteoporosis and acute mountain sickness.
Aspirins dark side
In many cases, aspirins side effects are part and parcel of its promoted effects. For example, aspirin reduces second heart attacks and ischemic strokes because it decreases platelet aggregation, inhibiting clotting. This action may also explain why aspirin seems to raise the risk of hemorrhagic strokes, which are caused by bleeding in the brain.
Despite some of its serious side effects, aspirin is comparatively safe. In cases involving individuals with a history of myocardial infarction, it is estimated that for every 1000 patients who take aspirin each year, 40 subsequent heart attacks are prevented and there is only one episode of bloody vomiting (11).
Another approach is to eschew aspirin in favor of less-irritating NSAIDs. Older NSAIDs inhibit both forms of cyclooxygenase. However, it is believed that only COX-2 plays a role in inflammation and only COX-1 is involved in maintaining the stomach lining. In the case of aspirin, the inhibition of COX-1 is 10100 times greater than its inhibition of COX-2. Thus, drugs that primarily inhibit COX-2, such as celecoxib (Celebrex) and rofecoxib (Vioxx), should calm inflammation and not irritate the stomachalthough possibly at the cost of slower healing.
Other new drugs are still under development, such as NSAIDs combined with agents that protect the stomach. Some researchers have modified aspirin molecules by adding side chains that release nitric oxide. The release of nitric oxide counteracts the loss of prostacyclin, preserves the blood flow that protects gastric mucosa, and increases gastric mucus synthesis (12).
But swapping one drug for another is not always an option. For people wishing to prevent a second heart attack or stroke, aspirin remains the drug of choice. Other NSAIDs have not been shown to have aspirins benefits to the circulatory system. However, unlike the high doses needed to treat arthritis pain, cardiovascular benefits occur at even low doses and thus produce fewer side effects. For example, the risk of ischemic stroke is cut by the same 15% regardless of whether the daily aspirin dose is 50 mg or 1500 mg (13).
Aspirin stands poised to remain as important in the 21st century as it was in the 20th. But the transition from a therapeutic to a preventive medicine requires thoughtful balancing of risks and benefits. The perception of aspirin as innocuousexemplified by the advice to take two aspirin and call me in the morningmust give way to a respect for its potency.
Shauna S. Roberts is a science and medical writer and editor in New Orleans. Comments and questions for the authors may be addressed to the Editorial Office by e-mail at email@example.com, by fax at 202-776-8166 or by post at 1155 16th Street, NW; Washington, DC 20036.