UCSF study reveals common patient group at high risk for stroke

December 12, 2000

People who experience transient ischemic attack (TIA), a fleeting condition that amounts to an aborted stroke, are often at high risk for experiencing a full-fledged stroke or other serious adverse effects within the first 90 days following their diagnosis of TIA, according to a large-scale epidemiology study led by UCSF neurologists.

The finding, reported in the December 13 issue of the Journal of the American Medical Association (JAMA), offers important insight into a condition that afflicts 300,000 patients in the United States each year and which is not only difficult to diagnose but whose effect on stroke risk has been unclear.

It also suggests, says the lead author of the study, S. Claiborne Johnston, MD, MPH, UCSF assistant professor of neurology, that many TIA patients should be treated more aggressively with existing, and perhaps novel, therapies aimed at preventing the onset of stroke.

"Our results indicate that transient ischemic attacks can be ominous, carrying a substantial short-term risk of stroke, hospitalization for cardiovascular events and death in people with transient ischemic attack," says Johnston. "Aggressive treatments aimed at preventing stroke in TIA patients could significantly reduce the overall stroke incidence, and the efficacy of such intervention should be studied."

TIA, like ischemic stroke, results from a blood clot blockage in the arteries leading to the brain or in the brain itself. The clot disrupts some part of brain function. However, while the symptoms of both conditions - weakness, numbness in limbs, decreased mobility, difficulty speaking, and double vision - are identical, they dissipate within a minute to 24 hours in TIA and are usually permanent in stroke victims. And while patients with TIA generally do not have permanent damage to brain tissue, stroke victims do. Basically, says Johnston, TIA is a stroke interrupted.

One of the difficulties in treating TIA patients is that their symptoms, and the clot itself, have generally dissipated by the time the patients receive medical evaluation. And while some interventions are known to be effective in reducing the risk of stroke after TIA, it has not been known whether more urgent therapy is justified.

Some patients, especially those with very brief episodes, wait out their symptoms at home. But in those who seek evaluation, treatment varies widely, with some institutions admitting all patients and others providing outpatient evaluations. Admitted patients generally receive a more rapid work-up, and treatment is usually more aggressive.

The reason for the different treatment approaches, says Johnston, has been due largely to the lack of sufficient data evaluating the short-term risk of stroke following TIA.

The current study evaluated 1,707 patients with a mean age of 72 seen in the emergency departments of 16 hospitals in northern California between March 1997 and February 1998. The patients were all evaluated within one day of the onset of symptoms. The hospitals were associated with the Kaiser-Permanente health maintenance organization, and the patients in the study generally received the standard evaluation and treatment for TIA, according to Johnston.

The results showed that the risk of stroke in the 90 days post evaluation for TIA was 10.5 percent. This translated to 180 cases of stroke, more than 50 times the number expected in people of similar age. Half of the strokes occurred in the first two days following the TIA. Moreover, short-term risks of cardiovascular events, death and recurrent TIA were also high, with a combined increased risk of 25.1 percent in the first three months following TIA.

Notably, the heightened risk for stroke was associated with five independent risk factors: age greater than 60, diabetes, duration of episode greater than 10 minutes, weakness and speech impairment. Targeting TIA patients who have these high-risk factors could be the key to reducing stroke incidence in TIA patients, says Johnston.

In some hospitals, all TIA patients seen in the emergency department are evaluated to determine if there is a blockage in their carotid arteries; in others, this evaluation is delayed for days or weeks. Patients who do have a blocked artery undergo an endarterectomy, a surgical procedure in which plaque is removed from the artery. Some patients with abnormal heart rhythms, such as atrial fibrillation, are treated with blood thinners. However, most patients don't have these conditions. They are given an anti-platelet agent, such as aspirin, and are released.

"Simply speeding up the timing of the patient evaluation and assuring that all TIA patients are treated with medications that have been proven to reduce stroke risk could help tremendously," says Johnston.

The use of additional therapies might be appropriate as well, he says. These could include more powerful strategies for blocking platelet function, such as combining aspirin and the newer drug clopidogrel, or using anticoagulant medications like heparin and Coumadin.

Results from the current study could be used to form a model to predict who is at highest risk for stroke after a TIA, says Johnston. Then, aggressive and potentially dangerous therapies that would be used only if deemed necessary could be targeted at those at highest risk.

However, before the findings could be incorporated into a prediction model for stroke, a large, perhaps multi-institutional, study in a different group of patients must be conducted to validate the results, says Johnston. Patients who admit themselves to a hospital emergency department most likely represent higher risk cases to begin with, notes Johnston. Those who show up in the outpatient clinics may be at lower risk.

Regardless, he says, the study demonstrates that a large number of TIA patients are at significant risk for stroke, and efforts should be made to improve their care. "We need to come up with better therapies for these people," he says. "This study shows room for improvement."
Co-authors of the study were Daryl R. Gress, MD, UCSF associate professor and director of the neurovascular service; Warren S. Browner, MD, MPH, UCSF associate professor of medicine at the San Francisco VA Medical Center and UCSF associate professor of medicine, epidemiology and biostatistics; and Stephen Sidney, MD, MPH, associate director for clinical research of the division of research at Kaiser Permanente Northern California, Oakland.

The study was funded by the American Heart Association, National Stroke Association and the National Institutes of Health.

University of California - San Francisco

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