Thrombectomy plus intra-arterial alteplase increases excellent functional outcome to 57.5% at 90 days

This was a randomized, open-label trial with blinded outcome assessment conducted at 14 stroke centers in Spain. The population included 440 patients with acute ischemic stroke due to large vessel occlusion who were treated with thrombectomy within 24 hours and achieved an expanded Treatment in Cerebral Ischemia score of 2b50 to 3. The intervention was thrombectomy plus intra-arterial alteplase at a dose of 0.225 mg/kg, with a maximum dose of 20 mg, infused over 15 minutes. The comparator was thrombectomy alone. The primary outcome was excellent functional outcome at 90 days, defined as a modified Rankin Scale score of 0 or 1.

The primary outcome results showed that 57.5% (123/214) of patients in the thrombectomy plus intra-arterial alteplase group achieved an excellent functional outcome, compared to 42.5% (93/219) in the thrombectomy alone group. The adjusted risk difference was 15.0% (95% CI, 5.7% to 24.3%; P = .002), indicating a statistically significant increase. Key secondary outcomes included residual hypoperfusion on follow-up computed tomography perfusion, which was lower in the combination group at 28.6% (55/192) versus 50.5% (96/190) in the thrombectomy alone group (adjusted risk difference, -22.0%; 95% CI, -31.5% to -12.4%; P < .001).

Symptomatic intracranial hemorrhage occurred in 1.4% (3/214) of the combination group versus 0.5% (1/219) of the thrombectomy alone group (adjusted odds ratio, 3.10; 95% CI, 0.32 to 30.0; P = .33), which was not statistically significant. Mortality at 90 days was higher in the combination group at 12.1% (26/214) versus 6.4% (14/219) in the thrombectomy alone group (adjusted risk difference, 5.9%; 95% CI, 0.5% to 11.3%; P = .03).

Safety findings focused on symptomatic intracranial hemorrhage as the primary adverse event and serious adverse event. The trial did not report data on discontinuations or overall tolerability. The higher mortality in the thrombectomy plus intra-arterial alteplase group was identified as a key limitation and warrants further study.

These results can be compared to prior landmark studies in acute ischemic stroke, such as the MR CLEAN and DAWN trials, which established the benefit of thrombectomy alone. This study adds evidence on the potential adjunctive role of intra-arterial alteplase, but the increased mortality raises questions about net clinical benefit.

Key methodological limitations include the open-label design, which could introduce performance bias, although outcome assessment was blinded. The study was conducted in a specific setting of 14 centers in Spain, which may limit generalizability to other regions or healthcare systems. Potential biases include selection bias in patient enrollment and the lack of reported funding or conflicts of interest.

Clinical implications suggest that while adjunctive intra-arterial alteplase may improve functional outcomes, the increased mortality requires careful consideration in practice decisions. Clinicians should weigh the benefits against the risks on an individual patient basis.

Unanswered questions include the optimal dosing and timing of intra-arterial alteplase, the mechanisms behind the increased mortality, and whether these findings replicate in larger, more diverse populations. Further research is needed to clarify the net clinical benefit and safety profile.