MedWire News: Stroke patients benefit from alteplase given between 3.0 and 4.5 hours after stroke, report the ECASS III investigators.
Thrombolysis is currently approved only in patients who present within 3 hours of symptom onset. But many patients present after this treatment window has elapsed.
Werner Hacke (University of Heidelberg, Germany) and the ECASS (European Cooperative Acute Stroke Study) III investigators now report in the New England Journal of Medicine that the benefits of thrombolysis continue to at least 4.5 hours after stroke, with no further increase in hemorrhage risk.
But editorialist Patrick Lyden (Veterans Affairs Medical Center, San Diego, California, USA) warned: "The very real peril of the ECASS III data is that some may take an even more leisurely approach to treating acute stroke.
"Nothing could be more wrong, for as we look back on the past decade of thrombolytic therapy for stroke, it is very clear that our focus must remain on the door-to-needle time. Every minute matters during a stroke."
A total of 821 patients were recruited to ECASS III and randomly assigned to receive intravenous alteplase 0.9 mg/kg or placebo. The average National Institutes of Health Stroke Scale (NIHSS) score was significantly lower, at 10.7, in the alteplase group than in the placebo group, at 11.6.
Patients in the alteplase group received the drug a median of 3 hours and 59 minutes after stroke onset, with most receiving it between 3.5 and 4.5 hours post-onset.
Symptomatic intracranial hemorrhage occurred in significantly more alteplase- than placebo-treated patients, at 2.4% versus 0.2%, but was low overall, while any intracranial hemorrhage occurred in 27.0% versus 17.6%.
For ECASS III, investigators blinded to treatment assignation determined whether neurologic deterioration was likely caused by hemorrhage as observed on brain imaging. The team also analyzed symptomatic hemorrhage according to previous study definitions, but again found that rates were low and comparable with those in other studies, despite the extended thrombolysis window in ECASS III.
Mortality was similar between the alteplase and placebo groups, at 7.7% and 8.4%, respectively.
At 3 months after stroke, 52.4% of alteplase-treated patients achieved a favorable outcome (modified Rankin Scale 0-1), compared with 45.2% of placebo-treated patients, equating to a 1.34-fold increase in the likelihood of a favorable outcome.
Similar results were found using a global outcome measure comprising four neurologic and disability scores (NIHSS, mRS, Barthel Index, Glasgow Outcome Scale), with a 1.28-fold increase in the likelihood of a favorable outcome associated with alteplase treatment.
"This effect size is clinically meaningful and thus extends the treatment window for patients who do not arrive at the hospital early," say Hacke et al.
"It does not mean, however, that patients who can be treated within 3 hours should have their treatment delayed."
Free abstract
