NEW YORK (Reuters Health) – For patients with cerebral ischemia, treatment with tissue plasminogen activator (TPA) is known to confer substantial benefit when given within 3 hours of symptom onset. Now, new research shows that even when TPA is given 3.0 to 4.5 hours later, the odds of benefiting the patient, although reduced, are still greater than the risk of harm.

The results of the third European Coopertive Acute Stroke Study (ECASS 3) showed that TPA has a statistically significant benefit when given in the 3.0 to 4.5-hour window, Dr. Jeffrey L. Saver and co-researchers note in the July issue of Stroke. However, they add, “an effect size estimate incorporating benefit and harm across all levels of poststroke disability has not previously been derived.”

In the current study, Dr. Saver, from the David Geffen School of Medicine at the University of California, Los Angeles, and colleagues conducted a joint outcome table analysis of the ECASS 3 data to determine the number of patients needed to treat to benefit or harm.

Using a model population of 1000 patients, the authors found that about half as many patients have a better outcome when treated 3.0 to 4.5 hours after symptom onset versus within 3.0 hours. They calculate that roughly six patients would need to be treated for one to have an improved outcome.

No increase in harmful effects was noted when TPA was delayed until the 3.0- to 4.5-hour window. About 37.5 patients would need to be treated for one to have a worse outcome than they would have had without treatment.

The authors calculate that for every 100 patients treated with TPA between 3.0 and 4.5 hours,16.3 would have an improved outcome and 2.7 would have a worse outcome.

In a meta-analysis also reported in Stroke, Dr. Maarten G. Landsberg, from Stanford University Medical Center, Palo Alto, California, and associates found, in agreement with the first study, that treatment with TPA 3.0 to 4.5 hours after symptom onset increased the likelihood of favorable outcomes without increasing mortality. The analysis included data from ECASS -1, -2, and -3 (n=821), as well as from the Alteplase Thrombolysis for Noninterventional Therapy (ATLANTIS) study (n=302).

Reference:
Stroke 2009;40:2433-2441.