Research Summary

Late-Window Alteplase Improves Functional Outcomes in Perfusion-Selected Ischemic Stroke Without Planned Thrombectomy

Miranda Manier, BA

Key Highlights

  • Functional independence at 90 days was higher with alteplase versus standard care (40% vs 26%; adjusted risk ratio [aRR], 1.52; 95% CI, 1.14–2.02; P = .004).
  • Symptomatic intracranial hemorrhage was more frequent with alteplase (3.8% vs 0.51%; aRR, 7.34; 95% CI, 1.54–34.84; P = .01).
  • Mortality at 90 days was the same in both groups (11%; aRR, 0.91; 95% CI, 0.52–1.62; P = .76).
  • Randomized, open-label, blinded end-point trial across 26 centers; patients selected by CT perfusion and had no initial plan for thrombectomy.

In a randomized, open-label, blinded end-point clinical trial conducted at 26 stroke centers, intravenous alteplase administered between 4.5 and 24 hours after acute ischemic stroke onset improved functional outcomes at 90 days compared with standard medical treatment among patients with imaging-confirmed salvageable brain tissue and no initial plan for endovascular thrombectomy. The absolute difference in independence was notable, with similar mortality, albeit with an increased risk of symptomatic intracranial hemorrhage.

The study addresses an evidence gap around the safety and efficacy of thrombolysis beyond 4.5 hours after onset. Extending treatment options for patients who present late yet demonstrate salvageable tissue on perfusion imaging is clinically relevant, particularly when thrombectomy is not planned at presentation.

Adults with acute ischemic stroke were eligible if they presented 4.5 to 24 hours after symptom onset (or midpoint between last known well and symptom recognition for unknown onset), had salvageable tissue on perfusion imaging, and did not have an initial plan for thrombectomy. Participants were randomized 1:1 to alteplase (0.9 mg/kg; maximum, 90 mg) or standard medical treatment. The primary efficacy outcome was functional independence—modified Rankin Scale (mRS) score 0–1—at 90 days. Safety outcomes included symptomatic intracranial hemorrhage within 36 hours and all-cause mortality within 90 days.

Among 372 randomized patients (median [IQR] age, 72 [64–80] years; 43% women), all completed follow-up. Functional independence at 90 days occurred in 40% of the alteplase group (75/186) versus 26% of the standard-care group (49/186), corresponding to an aRR of 1.52 (95% CI, 1.14–2.02; P = .004) and an unadjusted absolute risk difference of 13.98% (95% CI, 4.50%–23.45%). Symptomatic intracranial hemorrhage was more frequent with alteplase (3.8% vs 0.51%; aRR, 7.34; 95% CI, 1.54–34.84; P = .01; unadjusted risk difference, 3.23% [0.28%–6.19%]). Mortality at 90 days was identical between groups (11% each; aRR, 0.91; 95% CI, 0.52–1.62; P = .76; unadjusted risk difference, 0% [95% CI, −6.30% to 6.30%]).

“In patients with acute ischemic stroke with salvageable brain tissue identified by perfusion imaging who did not initially receive thrombectomy, intravenous alteplase administered 4.5 to 24 hours after onset provided functional benefit, despite an increase in symptomatic intracranial hemorrhage,” Ying Zhou, PhD and colleagues concluded.

Reference:
Zhou Y, He Y, Campbell BCV, et al. Alteplase for acute ischemic stroke at 4.5 to 24 Hours: the HOPE randomized clinical trial. JAMA. 2025:e2512063. doi:10.1001/jama.2025