{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T12:01:54Z","timestamp":1785240114758,"version":"3.55.0"},"reference-count":38,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["RFPS\u20102006\u20101\u2010336562"],"award-info":[{"award-number":["RFPS\u20102006\u20101\u2010336562"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Euro J of Neurology"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>In the early time window, direct mechanical thrombectomy (MT) is not non\u2010inferior to combined treatment with intravenous thrombolysis (IVT) for patients with large vessel occlusion (LVO) stroke, while its non\u2010inferiority in the extended time window remains uncertain. This study assessed whether direct MT is non\u2010inferior to IVT\u2009+\u2009MT beyond 4.5\u2009h or at wake\u2010up.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We emulated a non\u2010inferiority trial, comparing direct MT vs. IVT\u2009+\u2009MT, including patients with anterior circulation LVO between 4.5 and 24\u2009h from symptom onset or at wake\u2010up, without contraindications to IVT and with target perfusion mismatch. We used inverse probability weighting (IPW) adjusted for pre\u2010specified covariates. The primary outcome was 90\u2010day mRS 0\u20132, with non\u2010inferiority defined by a lower 95% CI boundary of the Risk Difference (RD)\u2009\u2265\u2009\u22121.3%.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among 347 patients, 212 received direct MT and 135 received IVT\u2009+\u2009MT. After IPW, patients treated with direct MT and IVT\u2009+\u2009MT had a similar likelihood of achieving a 90\u2010day mRS of 0\u20132 (adjRD \u20132.90 [95% CI \u20136.64 to 0.84]) with the lower boundary of the RD 95% CI crossing the non\u2010inferiority margin. Additionally, direct MT was associated with a shift toward a higher score on the 90\u2010day mRS (adjusted Common OR 1.59 [95% CI 1.05\u20132.39]), not confirmed after IPW, and with lower odds of successful recanalization (adjOR 0.38 [95% CI 0.18\u20130.78]). Rates of 90\u2010day mRS 0\u20131, sICH, and mortality were similar between groups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In our target trial emulation, direct MT was not non\u2010inferior to IVT\u2009+\u2009MT treatment beyond 4.5\u2009h from symptom onset or at wake\u2010up, with IVT before MT yielding higher successful recanalization rates.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/ene.70682","type":"journal-article","created":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T05:12:24Z","timestamp":1782969144000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Direct Thrombectomy vs. Combined Treatment With Intravenous Thrombolysis in the Extended Time Window: A Target Trial Emulation"],"prefix":"10.1111","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8481-6327","authenticated-orcid":false,"given":"Ettore","family":"Nicolini","sequence":"first","affiliation":[{"name":"Department of Human Neurosciences Sapienza University of Rome  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3282-4672","authenticated-orcid":false,"given":"Antonio","family":"Ciacciarelli","sequence":"additional","affiliation":[{"name":"Stroke Unit, Policlinico Umberto I Sapienza University of Rome  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Pracucci","sequence":"additional","affiliation":[{"name":"Department of NEUROFARBA, Neuroscience Section University of Florence  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Saia","sequence":"additional","affiliation":[{"name":"Neurology and Stroke Unit S. 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