Every 15-minute increment of time saved until patients with acute ischemic stroke receive tissue plasminogen activator was associated with fewer deaths and greater numbers of patients discharged with improved ambulation or to their home in the largest study to date of real-world experience with TPA.
The report, which used patients with longer intervals between symptom onset and TPA administration as a reference group, also showed that patients who received TPA earlier had fewer symptomatic intracranial hemorrhages, Dr. Jeffrey L. Saver and his associates reported. The report was published June 19 in JAMA. Dr. Saver is director of the stroke and vascular neurology clinic at the University of California, Los Angeles.
Dr. Jeffrey L. Saver
Given 1,000 treated patients, every 15-minute increment of time saved until administration of TPA was associated with 4 fewer in-hospital deaths, 18 more patients having improved ambulation at discharge, and 13 more patients being discharged to an independent environment, the investigators noted (JAMA 2013;309:2480-8).
These findings confirm and extend the results of several formal but small clinical trials of TPA. With a study population more than 30 times larger than that of all patients who took part in TPA clinical trials, the results of this study demonstrate a much greater magnitude of benefit than previous studies were able to do.
Until now, it was not certain that the benefits of early TPA administration shown in clinical trials would generalize to more diverse patients and hospitals in real-world practice, Dr. Saver and his colleagues said.
"The findings from this study emphasize the importance of worldwide efforts to shorten onset to lytic treatment times for acute ischemic stroke," they wrote.
The investigators used data in the Get With The Guidelines–Stroke registry of the American Heart Association and the American Stroke Association, which collects information on consecutive stroke and transient ischemic attack (TIA) patients admitted to hospital emergency departments across the country. They focused on 58,353 patients admitted to 1,395 participating sites during a 10-year period who received IV TPA within the 4.5 hours of symptom onset recommended in current national guidelines.
Median patient age was 72 years. The study population was equally divided between men and women. The mean interval between symptom onset and administration of TPA was 144 minutes.
A total of 5,404 patients (9.3% of the study population) received TPA within 90 minutes, while 45,029 (77.2%) received it at 91-180 minutes, and 7,920 (13.5%) received it at 181-270 minutes.
Overall, there were 5,142 (8.8%) in-hospital deaths. A total of 2,873 patients (4.9%) had intracranial hemorrhage, 22,541 (38.6%) were discharged home, and 19,491 (33.4%) were able to walk independently at discharge.
Faster TPA administration was associated with several positive outcomes. For every 15-minute-faster interval before treatment, mortality was less likely to occur (odds ratio = 0.96), symptomatic intracranial hemorrhage was less likely to occur (OR = 0.96; 95% confidence interval, 0.95-0.98), independent ambulation was more likely to occur (OR = 1.04; 95% CI, 1.03-1.05), and discharge home rather than to a care facility was more likely to occur (OR = 1.03; 95% CI, 1.02-1.04), Dr. Saver and his colleagues said.
These associations remained robust in several further analyses of the data. They also remained consistent across subgroups of patients regardless of age, sex, race/ethnicity, and the severity of stroke at presentation.
"These findings support intensive efforts to accelerate patient presentation and to streamline regional and hospital systems of acute stroke care" so as to shorten the interval between symptom onset and TPA administration, the investigators added.
The Get With The Guidelines–Stroke program of the American Heart Association and the American Stroke Association is supported in part by Janssen Pharmaceuticals. Dr. Saver reported ties to Covidien, CoAxia, Grifols, Brainsgate, Lundbeck, and St. Jude Medical; his associates reported ties to numerous industry sources.