SAN DIEGO — Treatment of stroke with tissue plasminogen activator within 4.5 hours of stroke onset reduces disability regardless of age or stroke severity, researchers reported at the International Stroke Conference.
Tissue plasminogen activator (tPA) is the only FDA-approved treatment for acute ischemic stroke; however, there is still debate regarding the appropriate time window and its use in older patients or those with a minor or severe stroke, Jonathan Emberson, PhD, from the University of Oxford, said at a press conference.
Emberson and colleagues performed a meta-analysis of nine trials (n=6,756) that compared recombinant tPA with placebo or open control therapy.
tPA effective up to 4.5 hours
Patients who received tPA within 3 hours of stroke onset had a higher rate of modified Rankin score of 0 or 1 compared with controls (33% vs. 23%; OR=1.75; 95% CI, 1.35-2.27). The difference remained in patients who received tPA between 3 hours and 4.5 hours of stroke onset (35% vs. 30%; OR=1.26; 95% CI, 1.05-1.51), but not for those who received tPA more than 4.5 hours after onset (tPA group, 33%; control group, 31%; OR=1.15; 95% CI, 0.95-1.4).
Emberson said the benefits of treatment were similar regardless of age or stroke severity. “Importantly, there was clear evidence of benefit in patients older than 80 years,” he said.
The treatment groups did not differ in rates of 90-day mortality (tPA group, 17.9%; control group, 16.5%; HR=1.11; 95% CI, 0.99-1.25) despite an early spike in intracranial hemorrhages, which were often fatal, in the tPA group. The RR for fatal intracranial hemorrhages within 7 days for the tPA group was 7.14 (95% CI, 3.98-12.8), Emberson said.
Because of that, the tPA group had a higher rate of mortality between 1 and 7 days compared with the control group (RR=1.39, 95% CI, 1.16-1.67), but not between 8 and 30 days (RR=0.97; 95% CI, 0.79-1.2) or between 31 and 90 days (RR=0.92; 95% CI, 0.74-1.15), he said.
“While tPA increases the early risk of death from intracranial hemorrhage, it has no significant effect on other causes of early death,” Emberson said at the press conference. “Among those treated earlier, there is a suggestion that this early hazard is followed by later mortality benefits.”
No reason for age restrictions
These findings could prompt changes to regulations and guidelines for use of tPA, said study co-author Kennedy R. Lees, MD, FRCP, from the University of Glasgow, Scotland.
“In the United States, the licensing position has not yet been extended to 4.5 hours, and we wonder whether that might be altered,” Lees said. “The guidelines in the United States say it’s entirely reasonable to treat out to 4.5 hours if you’re under [age] 80, but not over 80. It seems to me to be entirely reasonable that now everybody who is eligible for thrombolysis should be treated out to 4.5 hours as early as possible within that time and regardless of age. There’s no reason for an ageist policy. There’s no reason for difference in treatment if you happen to be over 80.” – by Erik Swain
For more information:
Emberson J. Plenary Session I: Abstract LB2. Presented at: International Stroke Conference 2014; Feb. 12-14, 2014; San Diego.
Disclosure: Emberson reports no relevant financial disclosures. Lees reports financial ties with Boehringer Ingelheim, Grifols and Lundbeck.