Thrombectomy 24 hours after stroke: beyond DAWN

Desai, Shashvat M; Haussen, Diogo C; Aghaebrahim, Amin; Al‐Bayati, Alhamza R; Santos, Roberta; Nogueira, Raul G; Jovin, Tudor G; Jadhav, Ashutosh P.

doi:10.1136/neurintsurg-2018-013923

Cited by 128 publications

(99 citation statements)

References 15 publications

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“…The RR of mortality or severe disability remained statistically significant regardless of whether studies were pooled based on maximum enrollment time greater or less than 6 hours after symptom onset or whether perfusion imaging was utilized (online supplementary table 5) This former finding appears to mirror trends in other studies showing the benefit of thrombectomy even at extended times to treatment 20 21…”

Section: Discussionmentioning

confidence: 61%

Mortality reduction after thrombectomy for acute intracranial large vessel occlusion: meta-analysis of randomized trials

Yaeger

Martini

Hardigan

et al. 2019

J NeuroIntervent Surg

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BackgroundThrombectomy for patients with emergent large vessel occlusion (ELVO) is currently recognized as the standard of care for appropriately selected patients. As proven in several randomized clinical trials and meta-analyses, treatment with thrombectomy lowers rates of poor functional outcomes after ELVO, compared with standard medical management. However, combined mortality rates of the most recent, high-quality clinical trials have not been collectively assessed.ObjectiveThe goal of this study was to assess the combined mortality rates of patients with ELVO following thrombectomy using data from the most recent, high-quality clinical trials.MethodsMeta-analysis was performed in clinical trials comparing thrombectomy and medical management for patients with anterior circulation ELVO. Cumulative rates of mortality (mRS 6) as well as mortality or severe disability (mRS 5-6) were calculated.ResultsTen clinical trials fit the inclusion criteria, including PISTE, REVASCAT, DAWN, THRACE, SWIFT PRIME, ESCAPE, DEFUSE 3, THERAPY, EXTEND-IA, and MR CLEAN, with 2233 patients assessed for mortality alone and 2229 for mortality or severe disability. There was a significantly reduced risk of death with thrombectomy compared with standard medical care (14.9% vs 18.3%, P=0.03; RR 0.81, 95% CI 0.67 to 0.98), as well as a reduced risk of mortality or severe disability (mRS 5–6) in ELVO patients treated with thrombectomy (21.1% vs 30.5%, P<0.0001; RR 0.69, 95% CI 0.60 to 0.80).ConclusionsOverall, these results suggest a lower risk of death, as well as death or severe disability, in patients with ELVO treated with thrombectomy compared with medical management alone.

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Section: Discussionmentioning

confidence: 61%

Mortality reduction after thrombectomy for acute intracranial large vessel occlusion: meta-analysis of randomized trials

Yaeger

Martini

Hardigan

et al. 2019

J NeuroIntervent Surg

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“…Significant benefits of clot removal up to 24 h after stroke onset was shown 34 and the effect of clot removal beyond 24 h was also suggested. 35 Our current results regarding enhanced presence of proinflammatory microglia/macrophages by clot derived substances indicates that thrombectomy would be not only important for blood flow restoration, but would also mitigate clot-borne neuroinflammation.…”

Section: Discussionmentioning

confidence: 64%

Clot-Derived Contaminants in Transplanted Bone Marrow Mononuclear Cells Impair the Therapeutic Effect in Stroke

Okinaka

Kikuchi-Taura

Takeuchi

et al. 2019

Stroke

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Background and Purpose— The beneficial effects of bone marrow mononuclear cell (BM-MNC) transplantation in preclinical experimental stroke have been reliably demonstrated. However, only overall modest effects in clinical trials were observed. We have investigated and reported a cause of the discrepancy between the preclinical and clinical studies. Methods— To investigate the possible cause of low efficacy of BM-MNC transplantation in experimental stroke, we have focused on blood clot formation, which is not uncommon in human bone marrow aspirates. To evaluate the effects of clot-derived contaminants in transplanted BM-MNC on stroke outcome, a murine stroke model was used. Results— We show that BM-MNC separated by an automatic cell isolator (Sepax2), which does not have the ability to remove clots, did not attenuate brain atrophy after stroke. In contrast, manually isolated, clot-free BM-MNC exerted therapeutic effects. Clot-derived contaminants were also transplanted intravenously to poststroke mice. We found that the transplanted contaminants were trapped at the peristroke area, which were associated with microglial/macrophage activation. Conclusions— Clot-derived contaminants in transplanted BM-MNC nullify therapeutic effects in experimental stroke. This may explain neutral results in clinical trials, especially in those using automated stem cell separators that lack the ability to remove clot-derived contaminants. Visual Overview— An online visual overview is available for this article.

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“…Eight randomized controlled trials have proven its efficacy and safety in patients with LVO presenting within 24 hours 1–3. EVT eligibility criteria are likely to expand even further into the ‘fringes’, as more and more data on the safety and efficacy of EVT beyond current guideline recommendations become available—for example, for patients with M2 occlusions4 and those presenting more than 24 hours from last known well 5. In fact, it is becoming increasingly difficult to find a patient subgroup which does not benefit from EVT.…”

mentioning

confidence: 99%

About antifragility and the challenge of dealing with endovascular therapy trials that fail to show a positive result

Goyal

Ospel

2019

J NeuroIntervent Surg

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Thrombectomy 24 hours after stroke: beyond DAWN

Cited by 128 publications

References 15 publications

Mortality reduction after thrombectomy for acute intracranial large vessel occlusion: meta-analysis of randomized trials

Mortality reduction after thrombectomy for acute intracranial large vessel occlusion: meta-analysis of randomized trials

Clot-Derived Contaminants in Transplanted Bone Marrow Mononuclear Cells Impair the Therapeutic Effect in Stroke

About antifragility and the challenge of dealing with endovascular therapy trials that fail to show a positive result

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