By Harvard Heart Letter. May 1999; 9(9)

That question arises nearly every day for many physicians, and it is sometimes asked with a hint that perhaps the doctor has been negligent in not recommending this inexpensive wonder drug. The potential of aspirin is, after all, well known by now. As described in previous issues of the Harvard Heart Letter, research has shown convincingly that aspirin can reduce the risk for heart attacks and strokes among people with heart disease and other cardiovascular conditions. Some studies also have reported that aspirin can help prevent heart attacks in individuals without known heart disease.

Many people have embraced aspirin as safe and effective for prevention of heart problems. One survey found that 30% of white Americans and 11% of African Americans already use aspirin for this purpose. Many doctors themselves down one of these little pills every day.

Why, then, don't physicians recommend aspirin as routinely as they measure their patients blood pressures? The fact is, experts continue to disagree on whether aspirin should be used to prevent heart problems in certain groups of people without known heart disease. A few doctors even question whether it should be recommended routinely for those individuals with cardiovascular disease who seem to have a low risk for future heart problems. The reason is that no drug is completely safe, not even aspirin.

The Flip Side

Aspirin helps prevent heart attacks and strokes by interfering with the normal function of platelets. These tiny blood cells are crucial to the formation of clots. When someone nicks the skin while shaving, for instance, platelets flock to the site of injury and form clumps that stop the loss of blood.

Aspirin in effect poisons platelets so that they do not form those clumps well. Some people who use aspirin occasionally may notice that they bleed longer from small cuts or may bruise more easily if they have taken aspirin recently. This minor annoyance can be a godsend, however, when platelets threaten to clump inside an artery in the body. If a blood vessel in the heart or the brain is injured by a rupturing atherosclerotic plaque, the collection of platelets can lead to a clot that completely blocks blood flow through the vessel. The damage may be sealed off, but now blood cannot get through the artery. The consequence can be a heart attack or a stroke. Through its effects on platelets, aspirin is believed to help reduce the number of heart attacks and strokes caused by blood clots. But the flip side of this beneficial effect is that aspirin actually increases a persons risk for another kind of stroke the type that results from a break in a blood vessel, followed by bleeding. Under normal circumstances, damage to an artery in the brain might be sealed off quickly. With aspirin in the bloodstream, that damage-control mechanism may fail. The result can be a major hemorrhagic stroke.

How Big a Risk?

Some insight into the seriousness of this side effect of aspirin was provided by the Physicians Health Study, the landmark trial directed by Harvard Heart Letter editorial board member Charles H. Hennekens, MD. In this trial, 22,071 male physicians age 40 to 84 were randomly assigned to receive 325 mg of aspirin or a placebo every day. After about five years of follow-up, there had been 23 hemorrhagic strokes in the physicians assigned to the aspirin group compared with 12 cases in the placebo group.

Another trial of aspirin in patients who had had a minor stroke or near stroke also found more than double the risk of hemorrhagic stroke. However, it has been difficult to get a reliable sense of the magnitude of risk posed by aspirin, in part because these events are quite rare. Thus, even in large trials like the Physicians Health Study, only a small number of hemorrhagic strokes occur.

To gain more perspective on the overall risks and benefits of aspirin, researchers recently pooled data from 16 different trials in which patients had been assigned to use aspirin or a placebo. There were a total of 55,462 patients in these studies, and all were followed for an average of 37 months. The dose of aspirin used in these studies ranged from 75 mg to 413 mg (the usual over-the-counter tablet contains 325 mg). (Journal of the American Medical Association, Vol. 280, No. 22, pp. 19301935.)

In this meta-analysis, the benefits of aspirin were consistent and impressive. Aspirin use was associated with a reduction of 137 heart attacks per 10,000 people using the drug. Aspirin was also associated with a reduction of 39 ischemic strokes (those due to blood clots) for every 10,000 people.

However, aspirin use was also associated with a clear increase in the risk for hemorrhagic strokes of 12 events per 10,000 people. This increased risk for strokes due to bleeding in the brain was found in people with and without cardiovascular disease, and in both older and younger patients. The dosage of aspirin did not seem to influence the risk either.

Aspirin on Top?

As disconcerting as this increase in risk for hemorrhagic stroke might be, the fact remains that the aspirin-users in these studies had a 15% lower rate of dying than those taking placebo and keeping people alive is generally considered the ultimate test of a medication. Aspirin therapy was also associated with about a 12% reduction in the total number of strokes, since the lower number of ischemic strokes more than offset the increase in hemorrhagic strokes. Therefore, the weighing of risks versus benefits seems to come out heavily on the side of aspirin. Why, then, isnt everyone taking this drug?

The main reason is that people vary in their likelihood of benefiting from aspirin and some people have a very low chance of benefiting at all. For example, a young or middle-aged person with no known cardiovascular disease has a very low chance of stroke or heart attack and therefore an even lower chance of benefiting from aspirin. An editorial that accompanied this meta-analysis calculated that a 40-year-old man with high blood pressure but an otherwise favorable risk factor profile and no history of heart disease had only a 0.1% per year risk of cardiovascular problems. For this person, the chances of a hemorrhagic stroke with aspirin use may prove greater than the chances of preventing a heart attack.

Case-By-Case

Right now, the bottom line on aspirin appears to be that it is a good idea for most patients with known coronary artery disease or those with a history of strokes or near-strokes. In these cases, the risk of serious problems caused by blood clots is sufficiently high that the risk of aspirin is warranted. Aspirin may be too risky, however, in people who have problems from bleeding stomach ulcers or prior hemorrhagic strokes.

People without known heart disease have a lower probability of heart attack or stroke, so for them the risk-benefit equation for aspirin is more likely to be a toss-up. These individuals should discuss the relative merits of aspirin with their physicians. There are however, cases where the benefits of aspirin clearly are worth the risks. An example would be a 60-year-old man with high cholesterol and a family history of heart disease.

I

n truth, there are no wonder drugs that is, there are no medications that can cure serious conditions without any side effects. However, aspirin comes pretty close. It has some marvelous benefits, it is probably the least expensive medication in the world, and its rate of serious complications is very low. But the rate of side effects is not zero. For that reason, people should be sure to discuss with their physicians the pros and cons of aspirin before either stopping or starting this therapy.