Alteplase effective up to 24 hours after stroke onset, trial finds
Forty percent of patients who received alteplase between 4.5 and 24 hours after stroke onset achieved functional independence at 90 days compared with 26% who received standard care, a Chinese trial showed.
Administering alteplase to patients with acute ischemic stroke between 4.5 and 24 hours after onset provided functional benefit, despite an increase in symptomatic intracranial hemorrhage, according to a Chinese trial.
A total of 372 stroke patients (median age, 72 years; 43% women) with imaging-confirmed salvageable brain tissue, regardless of the presence of large vessel occlusion, were randomized to receive IV alteplase (0.9 mg/kg; maximum dose, 90 mg; n=186) or standard medical treatment (n=186). The open-label, blinded endpoint trial was conducted at 26 stroke centers between June 2021 and June 2024, with a final follow-up in October 2024. All eligible patients had stroke onset (or midpoint between when they were last known to be well and symptom recognition if onset was unknown) of 4.5 to 24 hours prior to presentation, and no initial plan for endovascular thrombectomy.
The primary efficacy outcome was functional independence, defined as a modified Rankin Scale (mRS) score of 0 to 1 at 90 days and safety outcomes included symptomatic intracranial hemorrhage within 36 hours and all-cause mortality within 90 days. Findings were published by JAMA on Aug. 7.
At 90 days, 40.3% of patients in the alteplase group achieved functional independence compared with 26.3% of the control group (adjusted risk ratio, 1.52 [95% CI, 1.14 to 2.02] [P=0.004]; unadjusted risk difference, 13.98% [95% CI, 4.50% to 23.45%]). Incidence of symptomatic intracranial hemorrhage was higher with alteplase at 3.8% versus 0.51% with standard treatment (adjusted risk ratio, 7.34 [95% CI, 1.54 to 34.84] [P=0.01]; unadjusted risk difference, 3.23% [95% CI, 0.28% to 6.19%]). Both groups had a 90-day mortality rate of 10.8%.
Limitations to the trial include its open-label design and the exclusion of patients with planned thrombectomy.
The trial's broader imaging criteria, inclusion of distal occlusions, and flexibility in software use mean findings may be relevant to resource-constrained and geographically isolated settings, the authors wrote. The findings also “support extending the therapeutic window for [intravenous thrombolysis] in appropriately selected patients when endovascular thrombectomy is not initially planned or indicated,” they concluded.