Direct Thrombectomy vs. Combined Treatment With Intravenous Thrombolysis in the Extended Time Window: A Target Trial Emulation

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.

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Journal
European Journal of Neurology
Published
2026-07-01
DOI
https://doi.org/10.1111/ene.70682
Primary Topic
Acute Ischemic Stroke Management
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article
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article

Direct Thrombectomy vs. Combined Treatment With Intravenous Thrombolysis in the Extended Time Window: A Target Trial Emulation

Ilaria Casetta, Michele Alessiani, Giuseppe Carità, Marta Iacobucci et al.
European Journal of Neurology
Acute Ischemic Stroke Management
article

Direct Thrombectomy vs. Combined Treatment With Intravenous Thrombolysis in the Extended Time Window: A Target Trial Emulation

Ilaria Casetta, Michele Alessiani, Giuseppe Carità, Marta Iacobucci, Daniel Konda, Andrea Boghi, Guido Andrea Lazzarotti, Paolo Invernizzi, Valentina Saia, Mannino Mj, Alessio Comai, Ettore Nicolini, Andrea Naldi, Raffaele Augelli, Nicola Limbucci, Marco Andrighetti, R Tassi, A Saletti, Nicola Giannini, Antonio Ciacciarelli, Danilo Toni, S Mangiafico, Giuseppe Pelle, R Menozzi, Fabrizio Sallustio, Domenico Sergio Zimatore, Marcella Caggiula, Luca Allegretti, Alfredo Pauciulo, Matteo Alberti, Federica D’Agostino, Ruiz Ros, Enrica Franchini, Marco Filizzolo, Giovanni Bosco, Maria Ruggiero, Tiziana Tassinari, Mauro Bergui, Manuel Cappellari, Enrico Fainardi, the IRETAS group, Monia Russo, Manuela De Michele, Guido Bigliardi, Andrea Zini, Luigi Simonetti, Giovanni Pracucci, Stefano Vallone, Marco Longoni, Patrizia Nencini, Marco Petruzzellis, Alessandro Pezzini
article en

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.

European Journal of NeurologyVol. 33(7)
University of Rome Tor Vergata (IT), University of Ferrara (IT), Policlinico Umberto I (IT), Istituto Neurologico Mediterraneo (IT), Azienda Unita' Sanitaria Locale Di Modena (IT), Ospedale di Bolzano (IT), Azienda Ospedaliera Universitaria Integrata Verona (IT), Azienda Universitaria Ospedaliera Consorziale - Policlinico Bari (IT), Fondazione Ricerca Molinette (IT), AULSS 2 Marca Trevigiana (IT), Ospedale Vincenzo Cervello (IT), Azienda Unità Sanitaria Locale di Ferrara (IT), Azienda Ospedaliero-Universitaria di Modena (IT), Ospedale “M. Bufalini” di Cesena (IT), Azienda Ospedaliero-Universitaria Careggi (IT), Ospedale San Giovanni Bosco (IT), Istituto delle Scienze Neurologiche di Bologna (IT), Arcispedale Sant'Anna (IT), Società Italiana di Cardiologia Interventistica (IT), Azienda Ospedaliera Universitaria Senese (IT), Ospedale di Parma (IT), Azienda-Unita' Sanitaria Locale Di Cesena (IT), Policlinico Tor Vergata (IT), Ospedale Santa Maria Goretti (IT), Fondazione Poliambulanza Istituto Ospedaliero (IT), Ospedale Santa Maria della Misericordia di Rovigo (IT), Ospedale Vito Fazzi (IT), Azienda Sanitaria Locale Roma 3 (IT), Ospedale Santa Corona (IT), Azienda Ospedaliera Universitaria Pisana (IT), University of Florence (IT), University of Turin (IT), Sapienza University of Rome (IT)
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Openalex Percentile: Top 7%
Acute Ischemic Stroke Management
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