Direct Thrombectomy vs. Combined Treatment With Intravenous Thrombolysis in the Extended Time Window: A Target Trial Emulation
Ettore Nicolini, Antonio Ciacciarelli, Giovanni Pracucci, Valentina Saia, Luigi Simonetti, Andrea Zini, Valerio Da Ros, Federica D'agostino, Marta Iacobucci, Manuela De Michele, Marco Andrighetti, Rossana Tassi, Andra Saletti, Ilaria Casetta, Enrico Fainardi, Alfredo Pauciulo, Marcella Caggiula, Roberto Menozzi, Alessandro Pezzini, Stefano Vallone, Guido Bigliardi, Domenico Sergio Zimatore, Marco Petruzzellis, Alessio Comai, Enrica Franchini, Luca Allegretti, Tiziana Tassinari, Nicola Limbucci, Patrizia Nencini, Giuseppe Carità, Monia Russo, Marco Filizzolo, Marina Mannino, Maria Ruggiero, Marco Longoni, Andrea Boghi, Andrea Naldi, Mauro Bergui, Giovanni Bosco, Giuseppe Pelle, Michele Alessiani, Matteo Alberti, Paolo Invernizzi, Raffaele Augelli, Manuel Cappellari, Guido Andrea Lazzarotti, Nicola Giannini, Daniel Konda, Fabrizio Sallustio, Salvatore Mangiafico, Danilo Toni,ABSTRACT
Background
In the early time window, direct mechanical thrombectomy (MT) is not non‐inferior to combined treatment with intravenous thrombolysis (IVT) for patients with large vessel occlusion (LVO) stroke, while its non‐inferiority in the extended time window remains uncertain. This study assessed whether direct MT is non‐inferior to IVT + MT beyond 4.5 h or at wake‐up.
Methods
We emulated a non‐inferiority trial, comparing direct MT vs. IVT + MT, including patients with anterior circulation LVO between 4.5 and 24 h from symptom onset or at wake‐up, without contraindications to IVT and with target perfusion mismatch. We used inverse probability weighting (IPW) adjusted for pre‐specified covariates. The primary outcome was 90‐day mRS 0–2, with non‐inferiority defined by a lower 95% CI boundary of the Risk Difference (RD) ≥ −1.3%.
Results
Among 347 patients, 212 received direct MT and 135 received IVT + MT. After IPW, patients treated with direct MT and IVT + MT had a similar likelihood of achieving a 90‐day mRS of 0–2 (adjRD –2.90 [95% CI –6.64 to 0.84]) with the lower boundary of the RD 95% CI crossing the non‐inferiority margin. Additionally, direct MT was associated with a shift toward a higher score on the 90‐day mRS (adjusted Common OR 1.59 [95% CI 1.05–2.39]), not confirmed after IPW, and with lower odds of successful recanalization (adjOR 0.38 [95% CI 0.18–0.78]). Rates of 90‐day mRS 0–1, sICH, and mortality were similar between groups.
Conclusions
In our target trial emulation, direct MT was not non‐inferior to IVT + MT treatment beyond 4.5 h from symptom onset or at wake‐up, with IVT before MT yielding higher successful recanalization rates.