Thrombectomy alone versus intravenous alteplase plus thrombectomy in patients with stroke: an open-label, blinded-outcome, randomised non-inferiority trial

Fischer, Urs; Kaesmacher, Johannes; Strbian, Daniel; Eker, Omer; Cognard, C; Plattner, Patricia S; Bütikofer, Lukas; Mordasini, Pasquale; Deppeler, Sandro; Pereira, Vítor Mendes; Albucher, Jean François; Darcourt, Jean; Bourcier, Romain; Guillon, Benoı̂t; Papagiannaki, Chrysanthi; Ozkul-Wermester, Ozlem; Sibolt, Gerli; Tiainen, Marjaana; Gory, Benjamin; Richard, Sébastien; Liman, Jan; Ernst, Marielle; Boulanger, Marion; Barbier, Charlotte; Mechtouff, Laura; Zhang, Liqun; Marnat, Gaultier; Sibon, Igor; Nikoubashman, Omid; Reich, Arno; Consoli, Arturo; Lapergue, Bertrand; Ribó, Marc; Tomasello, Alejandro; Saleme, Suzana; Macian, Francisco; Moulin, Solène; Pagano, Paolo; Saliou, Guillaume; Carrera, Emmanuel; Janot, Kévin; Hernández‐Pérez, María; Pop, Raoul; Schiava, Lucie Della; Luft, Andreas R.; Piotin, Michel; Gentric, Jean Christophe; Pikula, Aleksandra; Pfeilschifter, Waltraud; Arnold, Marcel; Siddiqui, Adnan H.; Froehler, Michael T.; Furlan, Anthony J.; Chapot, René; Wiesmann, Martin; Machi, Paolo; Diener, Hans‐Christoph; Kulcsár, Zsolt; Bonati, Leo H.; Bassetti, Claudio L.; Mazighi, Mikaël; Liebeskind, David S; Saver, Jeffrey L.; Gralla, Jan

doi:10.1016/s0140-6736(22)00537-2

Cited by 193 publications

(147 citation statements)

References 31 publications

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“…Taken together, the results of this study suggest that there is no need for stopping IVT immediately before starting or after having completed the MT procedure in pa-tients with running alteplase administration. These results seem to be in line with the recently presented preliminary data from the SWIFT-DIRECT trial [24], as the investigated lysis group in this trial mainly consisted of mothership patients with short procedure times, making an overlapping lysis activity in this group probable. This actually raises the additional question if the positive trial results may be partially based on the positive effect of an overlapping lysis effect, and the results may have been less clear, if also transfer patients with no overlapping activity would have been included.…”

Section: Discussionsupporting

confidence: 88%

“…To the best of our knowledge, besides the CHOICE trial addressing an additional intra-arterial approach, there are no published data available investigating the problem we focused on in the actual study. One recent publication, also from the GSR investigators, found a better outcome in patients with inhouse bridging lysis (which should in many cases be overlapping to MT) compared to patients without lysis therapy [23,24]. But, although these data might also support the notion of the safety of concomitant lysis, their work does not address the same topic, as they compared K lysis vs. non-lysis patients and not unmitigated active lysis vs. previously iv-treated patients.…”

Section: Discussionmentioning

confidence: 98%

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Start, Stop, Continue? The Benefit of Overlapping Intravenous Thrombolysis and Mechanical Thrombectomy

Burian

Sepp²,

Lehm³

et al. 2022

Clin Neuroradiol

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Objective Here we compare the procedural and clinical outcome of patients undergoing thrombectomy with running thrombolysis to matched controls with completed intravenous therapy and an only marginally overlapping activity. Methods Patients from 25 sites in Germany were included, who presented with an acute ischemic stroke. Patients’ baseline characteristics (including ASPECTS, NIHSS and mRS), grade of reperfusion, and functional outcome 24 h and at day 90 after intervention were extracted from the German Stroke Registry (n = 2566). In a case-control design we stepwise matched the groups due to age, sex and time to groin puncture and time to flow restoration. Results In the initial cohort (overlap group n = 864, control group n = 1702) reperfusion status (median TICI in overlap group vs. control group: 3 vs. 2b), NIHSS after 24 h, early neurological improvement parameters, mRS at 24 h and at day 90 were significantly better in the overlap group (p < 0.001) with a similar risk of bleeding (2.9% vs. 2.4%) and death (18% vs. 22%). After adjustment mRS at day 90 still showed a trend for lower disability scores in the overlap group (3 IQR 1-5 vs. 3 IQR 1-6, p = 0.09). While comparable bleeding risk could be maintained (4% in both groups), there were significantly more deaths in the control group (18% vs. 30%, p = 0.006). Conclusion The presented results support the approach of continuing and completing a simultaneous administration of intravenous thrombolysis during mechanical thrombectomy procedures.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 98%

Start, Stop, Continue? The Benefit of Overlapping Intravenous Thrombolysis and Mechanical Thrombectomy

Burian

Sepp²,

Lehm³

et al. 2022

Clin Neuroradiol

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“…Data of six randomized trials comparing EVT alone with IVT prior to EVT are currently available. The Chinese DIRECT-MT and DEVT trials showed non-inferiority of EVT alone,3 4 while non-inferiority was not demonstrated in MR CLEAN-NO IV, DIRECT-SAFE, SKIP and SWIFT-DIRECT 5–9. Treatment-associated time metrics were differently distributed across these trials.…”

Section: Introductionmentioning

confidence: 89%

Influence of time metrics on the treatment effect of intravenous alteplase prior to endovascular treatment in MR CLEAN-NO IV

Rinkel

Treurniet

Kappelhof

et al. 2022

J NeuroIntervent Surg

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BackgroundWe assessed whether the treatment effect of intravenous alteplase (IVT) prior to endovascular treatment (EVT) on functional outcome is modified by time metrics.MethodsWe used data from all patients included in MR CLEAN-NO IV, a randomized trial of IVT followed by EVT versus EVT alone in patients who presented directly to EVT-capable hospitals. The primary outcome was the modified Rankin Scale score at 90 days. We used ordinal regression with a multiplicative interaction term to assess if the effect of IVT is modified by onset-to-randomization (OTR), onset-to-IV-needle (OTN), door-to-groin (DTG) or needle-to-groin (NTG) times. Secondary outcomes included successful reperfusion (extended Thrombolysis In Cerebral Infarction Scale 2b–3) and symptomatic intracranial hemorrhage (sICH).ResultsIn 539 included patients (266 allocated to IVT+EVT and 273 to EVT alone), median workflow times were OTR: 93 (IQR 71–145) min; OTN: 98 (IQR 75–156) min; DTG: 64 (IQR 51–78) min; and NTG: 28 (IQR 20–41) min. There was a significant association between worse outcomes and longer time intervals for all metrics except NTG. We found no interaction between any of the time metrics and IVT for the effect on functional outcome (p values for interaction: OTR=0.40, OTN=0.39, DTG=0.61, NTG=0.56). We also did not observe any significant interaction for successful reperfusion or sICH.ConclusionIn MR CLEAN-NO IV, the effect of IVT prior to EVT was not modified by OTR, OTN, DTG or NTG times. Our results do not support the use of these metrics to guide IVT treatment decisions prior to EVT in comprehensive stroke centres.Trial registration numberISRCTN80619088.

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“…SWIFT-DIRECT was an international, multicenter, randomized, open label, blinded endpoint (PROBE) trial assessing the non-inferiority of MT alone versus IVT+MT in patients presenting directly to one of 48 participating MT-capable stroke centers in Europe and Canada. The trial protocol11 and main results, including details of the methodology, have already been published 7. Patients were eligible if they had imaging-confirmed occlusion of the intracranial carotid artery and/or the first segment (M1) of the middle cerebral artery; were eligible to receive alteplase within 4.5 hours after they were last seen well; could undergo MT within 75 min of randomization; and had severe neurological deficits, defined as a National Institutes of Health Stroke Scale (NIHSS) score of ≥5.…”

Section: Methodsmentioning

confidence: 99%

“…Whether mechanical thrombectomy (MT) alone can be regarded as equally effective as MT combined with bridging intravenous thrombolysis (IVT+MT) for patients admitted directly to centers with endovascular treatment capability remains controversial 1 2. Two trials in Chinese patients demonstrated non-inferiority of MT alone,3 4 whereas three other trials failed to show non-inferiority 5–7. All these trials used generous non-inferiority margins, which are considerably less conservative than the proposed minimal clinically important difference or the margin considered to constitute reasonable comparability8 .…”

Section: Introductionmentioning

confidence: 99%

Time to treatment with bridging intravenous alteplase before endovascular treatment:subanalysis of the randomized controlled SWIFT-DIRECT trial

Meinel

Kaesmacher

Buetikofer

et al. 2022

J NeuroIntervent Surg

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BackgroundWe hypothesized that treatment delays might be an effect modifier regarding risks and benefits of intravenous thrombolysis (IVT) before mechanical thrombectomy (MT).MethodsWe used the dataset of the SWIFT-DIRECT trial, which randomized 408 patients to IVT+MT or MT alone. Potential interactions between assignment to IVT+MT and expected time from onset-to-needle (OTN) as well as expected time from door-to-needle (DTN) were included in regression models. The primary outcome was functional independence (modified Rankin Scale (mRS) 0–2) at 3 months. Secondary outcomes included mRS shift, mortality, recanalization rates, and (symptomatic) intracranial hemorrhage at 24 hours.ResultsWe included 408 patients (IVT+MT 207, MT 201, median age 72 years (IQR 64–81), 209 (51.2%) female). The expected median OTN and DTN were 142 min and 54 min in the IVT+MT group and 129 min and 51 min in the MT alone group. Overall, there was no significant interaction between OTN and bridging IVT assignment regarding either the functional (adjusted OR (aOR) 0.76, 95% CI 0.45 to 1.30) and safety outcomes or the recanalization rates. Analysis of in-hospital delays showed no significant interaction between DTN and bridging IVT assignment regarding the dichotomized functional outcome (aOR 0.48, 95% CI 0.14 to 1.62), but the shift and mortality analyses suggested a greater benefit of IVT when in-hospital delays were short.ConclusionsWe found no evidence that the effect of bridging IVT on functional independence is modified by overall or in-hospital treatment delays. Considering its low power, this subgroup analysis could have missed a clinically important effect, and exploratory analysis of secondary clinical outcomes indicated a potentially favorable effect of IVT with shorter in-hospital delays. Heterogeneity of the IVT effect size before MT should be further analyzed in individual patient meta-analysis of comparable trials.Trial registration numberURL: https://www.clinicaltrials.gov ; Unique identifier: NCT03192332

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Thrombectomy alone versus intravenous alteplase plus thrombectomy in patients with stroke: an open-label, blinded-outcome, randomised non-inferiority trial

Cited by 193 publications

References 31 publications

Start, Stop, Continue? The Benefit of Overlapping Intravenous Thrombolysis and Mechanical Thrombectomy

Start, Stop, Continue? The Benefit of Overlapping Intravenous Thrombolysis and Mechanical Thrombectomy

Influence of time metrics on the treatment effect of intravenous alteplase prior to endovascular treatment in MR CLEAN-NO IV

Time to treatment with bridging intravenous alteplase before endovascular treatment:subanalysis of the randomized controlled SWIFT-DIRECT trial

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