Intra‐Arterial Alteplase After Successful Endovascular Reperfusion in Patients Without Intravenous Thrombolysis: A Subgroup Analysis of the PEARL Randomized Clinical Trial

Background For patients with large‐vessel occlusion stroke who undergo endovascular thrombectomy without prior intravenous thrombolysis, the efficacy and safety of adjunctive intra‐arterial alteplase (IAA) after successful endovascular reperfusion remain uncertain. Methods This was a prespecified subgroup analysis of the PEARL (Intra‐Arterial Alteplase After Successful Endovascular Reperfusion in Acute Stroke) randomized clinical trial conducted at 28 centers in China, focusing on patients who underwent endovascular thrombectomy without prior intravenous thrombolysis. Patients were stratified by treatment assignment: IAA treatment versus standard treatment (control). The primary efficacy outcome was the proportion of patients achieving excellent functional outcome, defined as a modified Rankin Scale score of 0 to 1 at 90 days. Safety outcomes included symptomatic intracranial hemorrhage, any intracranial hemorrhage within 36 hours, and 90‐day all‐cause mortality. Results Among 324 patients originally randomized in the PEARL trial, 189 underwent endovascular thrombectomy without prior intravenous thrombolysis and were included in this analysis. Of the 189 patients, 95 were assigned to the IAA treatment group and 94 to the standard treatment group. Excellent functional outcome at 90 days was significantly higher in the IAA treatment group compared with the standard treatment group (43.2% [41/95] versus 22.6% [21/93]; adjusted risk ratio [aRR], 1.86; 95% CI, 1.19–2.91; P= 0.007). The absolute risk reduction was 20.6% (95% CI, 7.0%–33.1%). Results were consistent in per‐protocol sensitivity analyses ( P= 0.002). No significant differences were observed in symptomatic intracranial hemorrhage (aRR, 0.93; 95% CI, 0.28–3.13; P= 0.908), any intracranial hemorrhage (aRR, 1.04; 95% CI, 0.68–1.60; P= 0.843), or 90‐day mortality (hazard ratio [HR], 1.00; 95% CI, 0.49–2.04; P >0.99). Conclusions In patients who did not receive prior intravenous thrombolysis, adjunctive IAA after successful endovascular thrombectomy was associated with a higher likelihood of excellent functional outcome at 90 days, without an apparent increase in symptomatic intracranial hemorrhage or mortality. Registration URL: clinicaltrials.gov ; Unique Identifier: NCT05856851.