A stroke occurs when the supply of blood to the brain is interrupted. A temporary interruption of blood flow is referred to as a transient ischemic attack (TIA) . Blood carries oxygen and other nutrients to brain cells; when they are deprived of this nourishment, they begin to die.

Most strokes are ischemic strokes, meaning that they are caused by the blockage of a blood vessel supplying the brain. An intracranial stenosis is one type of blockage resulting from atherosclerotic plaques that may lead to an ischemic stroke. Intracranial stenoses are responsible for about 10% of the 900,000 strokes and TIAs that occur in the United States each year. People with intracranial stenosis have a 15% chance of having a recurrent stroke each year.

Since the 1950s, physicians have treated intracranial stenosis patients with drugs such as aspirin and warfarin, which reduce blood clotting. Studies have not clearly shown which of the two therapies is more effective, and a recent survey showed that neurologists in the United States are pretty evenly divided between those who prefer aspirin and those who prefer warfarin.

In a randomized, double-blind study published in the March 31, 2005 New England Journal of Medicine , scientists compared the effectiveness of aspirin and warfarin in stroke or TIA patients with intracranial stenosis. They found that patients taking aspirin were significantly less likely to die, to have major bleeding (hemorrhaging), or a heart attack than patients taking warfarin. However, the likelihood of having a recurrent ischemic stroke, a brain hemorrhage, or death from vascular causes other than stroke were not significantly different between the two groups.

About the Study

The researchers recruited 569 patients, aged 40 years and older, who had had a TIA or nondisabling stroke in the previous three months. The TIAs or strokes were all caused by an atherosclerotic blockage that narrowed a major blood vessel in the brain by 50% to 99%.

The study subjects were randomly assigned to receive either 650 milligrams (mg) of aspirin twice a day, or 5 mg of warfarin each day. All patients underwent a monthly blood test to determine their international normalized ratio (INR), a measure that indicates whether the patient is being given an appropriate dose of warfarin. (The target INR ratio is 2.0-3.0.) Adjustments to the warfarin dose were made based on the INR test results. None of the study scientists or the study subjects were aware of who was taking aspirin and who was taking warfarin.

The scientists compared the incidences of ischemic stroke, major hemorrhage, heart attack, and death from vascular (relating to blood vessels) causes in the groups taking aspirin and warfarin.

The Findings

During a follow-up period averaging 1.8 years, the researchers found that patients taking aspirin were:

  • 54% less likely to die (4.3% vs. 9.7%)
  • 61% less likely to have a major hemorrhage (3.2% vs. 8.3%)
  • 60% less likely to have a heart attack or sudden death (2.9% vs. 7.3%)

These were all significant differences.

On the other hand, the rate of death from vascular causes (which included ischemic stroke) was not significantly different between the two groups. In addition, they found that about 22% of the patients experienced one of the primary endpoints (ischemic stroke, brain hemorrhage, or death from vascular causes other than stroke) regardless of whether they were taking aspirin or warfarin. This study was stopped early because of concern for the safety of patients taking warfarin.

The study results were limited by the fact that patients taking warfarin were only within their target INR 63% of the time.

How Does This Affect You?

The researchers found that patients with intracranial stenoses who had previously suffered a stroke or TIA were significantly less likely to die from any cause or have a major hemorrhage if they were taking aspirin as opposed to warfarin. Importantly, however, patients in both groups had a similar chance of having a recurrent ischemic stroke, brain hemorrhage, or dying from another blood vessel-related cause.

The idea of replacing warfarin therapy with aspirin therapy is a tempting one. For one thing, warfarin is substantially more expensive than aspirin. Also, as the researchers found, it is not easy to keep a patient within the target INR range for warfarin. As a result, warfarin dosing must be frequently adjusted to stay within the optimal range.

In this study, patients were in their target INR range only 63% of the time. According to the study authors, the percentage of patients within the target INR range in real, clinical practice is even lower than 63%. This is an important point because in this study, warfarin patients with a target INR were significantly less likely to have an ischemic stroke than patients who were above or below the target range.

But aspirin—in particular the dose of aspirin chosen for this study—could be problematic as well. Aspirin can increase the risk of gastrointestinal bleeding. And 1,300 mg per day is well above the aspirin dose typically prescribed to prevent heart attacks, which is only 325 mg per day. Further research would be needed to determine whether lower doses of aspirin could also be effective for stroke prevention.