Aspirin in the prevention of heart attack and stroke - a big study, no final answer
(June 2006)

Low-dose aspirin is advocated by many for the prevention of heart attack and stroke. Healthful Life has supported its use for those who have suffered a minor stroke (transient ischemic attack), for those who have suffered a heart attack, and for those who have certain heart rhythm abnormalities. But, we have not endorsed its routine use because, although it lowers the risk of heart attack somewhat (mainly in men), it does not reduce heart attack deaths and it increases the risk of bleeding.

A new, much ballyhooed study appeared in the Journal of the American Medical Association , January 18, 2006. It is a careful meta-analysis that combines the results of six already published studies. That gives them large numbers of participants, 51,342 women and 44, 114 men. Three of the six studies involved healthy men or women; in two other studies, the participants had one or more major risk factors for heart attack and stroke; and the final study focused on hypertensive men and women.

The summary results showed a major difference between men and women. Men showed a 32 percent reduction in heart attacks, but no reduction in stroke occurrence. Women, on the other hand, showed a 24 percent reduction in occurrence of strokes due to reduced blood supply to the brain, but no reduction in occurrence of heart attacks. In both men and women, there was no reduction in deaths due to heart attack or stroke. The risk of major bleeding was increased by 68 to 72 percent. Although most major bleeding occurred in the intestinal tract, there was also a 70 percent, statistically increased risk of hemorrhage into the brain among men. In women, there was only a slight increase in brain hemorrhage.

Two sentences in the discussion are worth quoting verbatim.

“Aspirin therapy for an average of 6.4 years results in an average absolute benefit of approximately three cardiovascular events (strokes) prevented per 1,000 women and four cardiovascular events (heart attacks) prevented per 1,000 men.”

There was “an average absolute increase of approximately 2.5 major bleeding events caused per 1,000 women and three major bleeding events caused per 1,000 men”.

The authors conclude that doctors should discuss both the benefits and harms before starting long-term aspirin treatment.

Commentary: This is a perfectly good study, but it still leaves us in a quandary. The benefit of three to four reduced non-fatal strokes or non-fatal heart attacks per 1,000 men or women is balanced by major bleeding in two and one-half to three women and men. And, that includes a significant amount of bleeding into the head in men. That means that some men and women given aspirin who are not destined to develop a heart attack or stroke will develop major bleeding, including brain hemorrhage. Because there is no evidence that aspirin reduces deaths, the limited potential benefit of aspirin may not be worth the potential risk of a major bleed.

There is another concern. The investigators have too little information about the possibility that aspirin users had lower blood pressure or had better controlled high blood pressure. If they had less uncontrolled hypertension or less pre-hypertension (blood pressure systolic 130 to 139 millimeters of mercury and/or diastolic 85 to 89 millimeters of mercury) than controls, they would be expected to have a lesser occurrence of stroke (high blood pressure is the major risk factor) and heart attack (high blood pressure is an important risk factor). So, some of the apparent benefit could be related to blood pressure differences in the aspirin-treated and control groups.