Adjunctive intra-arterial alteplase after near-complete or complete reperfusion in acute ischemic stroke: A post hoc analysis of the PEARL Trial

Background: The benefit of adjunctive intra-arterial alteplase treatment following near-complete to complete reperfusion (expanded thrombolysis in cerebral infarction (eTICI) scale of 2c to 3) by mechanical thrombectomy for acute large vessel occlusion stroke remains controversial. Aims: The study aimed to explore whether intra-arterial alteplase was associated with improved outcomes in patients with eTICI 2c/3 after thrombectomy compared with standard treatment. Methods: This post hoc analysis used data from the PEARL (Intra-arterial Alteplase for Acute Ischemic Stroke After Mechanical Thrombectomy) randomized controlled trial conducted at 28 sites in China. Patients with anterior circulation large-vessel occlusion who achieved eTICI 2c/3 reperfusion after mechanical thrombectomy were included. Patients were randomized to intra-arterial alteplase or standard medical treatment. The primary outcome was the distribution of modified Rankin Scale (mRS) scores at 90 days. Safety outcomes included intracranial hemorrhage and symptomatic intracranial hemorrhage within 36 h and mortality at 90 days. Results: Of 324 randomized patients in the PEARL trial, 136 were included in this analysis, with 65 assigned to intra-arterial alteplase and 71 to standard medical treatment. Compared with standard medical treatment, intra-arterial alteplase was associated with a favorable shift in 90-day functional outcome (common odds ratio, 2.07 [95% confidence interval (CI), 1.10–3.92]; P = 0.02). Rates of intracranial hemorrhage (adjusted risk ratio, 1.06 [95% CI, 0.62–1.83]; P = 0.82), symptomatic intracranial hemorrhage within 36 h (adjusted risk ratio, 0.29 [95% CI, 0.03–2.82]; P = 0.29), and mortality at 90 days (adjusted hazard ratio, 0.97 [95% CI, 0.29–3.28]; P = 0.96) did not differ significantly between groups, although the number of safety events was low. Conclusion: Among patients in the PEARL trial who achieved near-complete to complete reperfusion after mechanical thrombectomy, adjunctive intra-arterial alteplase was associated with improved functional outcomes at 90 days. Owing to the small sample size of this study, a pooled analysis of intra-arterial alteplase in patients with eTICI 2c/3 is needed to confirm these results. Registration: Clinicaltrials.gov identifier: NCT05856851.