Aspirin: The Cardiologist's Dream?

By Dick Thompson/Washington

Medical researchers have long known that taking regular doses of aspirin lowers the incidence of heart attack in some people with cardiovascular disease, the nation's leading killer. In study after study since the 1960s, however, they have sought to determine whether aspirin can help prevent heart trouble in healthy individuals. The results have been mixed: while some studies showed that aspirin decreased the number of attacks, others failed to demonstrate any benefit at all. Last week a report in the New England Journal of Medicine found that taking one aspirin every other day dramatically reduced the risk of an initial heart attack by 47%. Almost simultaneously, another study published in the British Medical Journal found that aspirin made little difference in thwarting heart trouble. Nonetheless, insisted Charles Hennekens, chief investigator in the U.S. trial and himself a test subject, "our study provides the first conclusive evidence that aspirin will reduce the risk of fatal and nonfatal heart attacks in otherwise healthy men."

The $4.4 million, six-year U.S. study, conducted by Brigham and Women's Hospital in Boston, covered 22,071 male physicians, ages 40 to 84, with no ) history of prior heart disease or stroke, for an average of 4.8 years. Half the group took a 325-mg tablet of aspirin every other day, the lowest dose the researchers considered both safe and effective; the other half received a placebo. This past December a board of medical experts monitoring the study decided that the results were "sufficiently compelling," as Yale Cardiologist Lawrence Cohen put it, to interrupt the study.

The data showed that while the placebo group had suffered 189 heart attacks, the group taking aspirin had only 104. Moreover, taking aspirin also produced a reduction in the number of cardiac deaths. Still, researchers were concerned that aspirin, which works by preventing clots in the bloodstream, might lead to an increase in certain kinds of strokes; the suspended study showed a slight increase of such strokes among the aspirin takers.

Results from the British trial were less conclusive. In a six-year study of 5,139 physicians, half took 500 mg of aspirin every day. Oxford University researchers found no reduction in heart attacks. They did see, however, a small but troubling excess of strokes. "Some things are clear," says Sir Richard Doll, who led the investigation. "For anybody who has had a heart attack in the past, it is beneficial to take a small dose of aspirin daily. That's unanimous. The dispute is over what healthy people should do."

The glaring difference in results may be explained by the varying sizes of the studies -- and the doses of aspirin consumed. The British doctors took almost twice as much aspirin twice as often as did their American counterparts. That led some researchers to speculate that too much aspirin may counteract the positive effects of lower doses. In addition, says Boston's Hennekens, the larger U.S. trial was far more conclusive statistically. "If you studied 5,000 doctors," he declares, "you'd have to follow them for 20 years to get the same results." Which report is to be believed? Says Sir Richard: "The truth is probably somewhere in between." In his view, aspirin may help prevent about 25% of heart attacks in healthy individuals.

If it even begins to measure up to the expectations of the U.S. study, aspirin could become the cardiologist's dream. It is inexpensive, readily available, effective in low dosages and relatively nontoxic for most people. First derived from willow bark and now chemically synthesized, aspirin works by blocking the manufacture of hormone-like chemicals called prostaglandins that are instrumental in the formation of blood clots.

But for many in the U.S., where 10 billion aspirin are consumed each year, there are also potentially serious side effects. These complications, including gastrointestinal distress, rectal bleeding and peptic ulcers, have caused researchers to temper their excitement over the implications of the American study and warn individuals not to take aspirin frequently except under a doctor's care. Says William Kannel, chief of preventive medicine at Boston University and a former director of the Framingham Study, a long-term heart-research program: "The most rational use would be in high-risk people, rather than having everyone gobble aspirin." Claude Lenfant, director of the National Heart, Lung and Blood Institute, cautions that for aspirin-sensitive people a suddenly increased intake of aspirin could be "tragic."

Nonetheless, many researchers guess that the proper use of aspirin could save 100,000 lives a year in the U.S. Heart disease, it seems, may be finally giving way to treatments both old and new, including both aspirin and artificial clot-dissolving drugs, and a growing concern about exercise, diet and smoking. But just how effective the familiar pills from the family medicine chest are in preventing heart attacks remains something of a mystery.