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  • BMJ  (17)
  • Fischer, Urs  (17)
  • 1
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    Antithrombotic regimen in emergent carotid stenting for acute ischemic stroke due to tandem occlusion: a meta-analysis of aggregate data
    BMJ ; 2023
    In:  Journal of NeuroInterventional Surgery
    Details
    In: Journal of NeuroInterventional Surgery, BMJ
    Abstract: The periprocedural antithrombotic regimen might affect the risk-benefit profile of emergent carotid artery stenting (eCAS) in patients with acute ischemic stroke (AIS) due to tandem lesions, especially after intravenous thrombolysis. We conducted a systematic review and meta-analysis to evaluate the safety and efficacy of antithrombotics following eCAS. Methods We followed PRISMA guidelines and searched MEDLINE, Embase, and Scopus from January 1, 2004 to November 30, 2022 for studies evaluating eCAS in tandem occlusion. The primary endpoint was 90-day good functional outcome. Secondary outcomes were symptomatic intracerebral hemorrhage, in-stent thrombosis, delayed stent thrombosis, and successful recanalization. Meta-analysis of proportions and meta-analysis of odds ratios were implemented. Results 34 studies with 1658 patients were included. We found that the use of no antiplatelets (noAPT), single antiplatelet (SAPT), dual antiplatelets (DAPT), or glycoprotein IIb/IIIa inhibitors (GPI) yielded similar rates of good functional outcomes, with a marginal benefit of GPI over SAPT (OR 1.88, 95% CI 1.05 to 3.35, P heterogeneity =0.31). Sensitivity analysis and meta-regression excluded a significant impact of intravenous thrombolysis and Alberta Stroke Program Early CT Score (ASPECTS). We observed no increase in symptomatic intracerebral hemorrhage (sICH) with DAPT or GPI compared with noAPT or SAPT. We also found similar rates of delayed stent thrombosis across groups, with acute in-stent thrombosis showing marginal, non-significant benefits from GPI and DAPT over SAPT and noAPT. Conclusions In AIS due to tandem occlusion, the periprocedural antithrombotic regimen of eCAS seems to have a marginal effect on good functional outcome. Overall, high intensity antithrombotic therapy may provide a marginal benefit on good functional outcome and carotid stent patency without a significant increase in risk of sICH.
    Type of Medium: Online Resource
    ISSN: 1759-8478 , 1759-8486
    URL: Article
    DOI: 10.1136/jnis-2023-020204
    Language: English
    Publisher: BMJ
    Publication Date: 2023
    detail.hit.zdb_id: 2506028-4
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  • 2
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    Safety and efficacy of intra-arterial fibrinolytics as adjunct to mechanical thrombectomy: a systematic review and meta-analysis of observational data
    BMJ ; 2021
    In:  Journal of NeuroInterventional Surgery Vol. 13, No. 12 ( 2021-12), p. 1073-1080
    Details
    In: Journal of NeuroInterventional Surgery, BMJ, Vol. 13, No. 12 ( 2021-12), p. 1073-1080
    Abstract: Achieving the best possible reperfusion is a key determinant of clinical outcome after mechanical thrombectomy (MT). However, data on the safety and efficacy of intra-arterial (IA) fibrinolytics as an adjunct to MT with the intention to improve reperfusion are sparse. Methods We performed a PROSPERO-registered (CRD42020149124) systematic review and meta-analysis accessing MEDLINE, PubMed, and Embase from January 1, 2000 to January 1, 2020. A random-effect estimate (Mantel-Haenszel) was computed and summary OR with 95% CI were used as a measure of added IA fibrinolytics versus control on the risk of symptomatic intracranial hemorrhage (sICH) and secondary endpoints (modified Rankin Scale ≤2, mortality at 90 days). Results The search identified six observational cohort studies and three observational datasets of MT randomized-controlled trial data reporting on IA fibrinolytics with MT as compared with MT alone, including 2797 patients (405 with additional IA fibrinolytics (100 urokinase (uPA), 305 tissue plasminogen activator (tPA)) and 2392 patients without IA fibrinolytics). Of 405 MT patients treated with additional IA fibrinolytics, 209 (51.6%) received prior intravenous tPA. We did not observe an increased risk of sICH after administration of IA fibrinolytics as adjunct to MT (OR 1.06, 95% CI 0.64 to 1.76), nor excess mortality (0.81, 95% CI 0.60 to 1.08). Although the mode of reporting was heterogeneous, some studies observed improved reperfusion after IA fibrinolytics. Conclusion The quality of evidence regarding peri-interventional administration of IA fibrinolytics in MT is low and limited to observational data. In highly selected patients, no increase in sICH was observed, but there is large uncertainty.
    Type of Medium: Online Resource
    ISSN: 1759-8478 , 1759-8486
    URL: Article
    DOI: 10.1136/neurintsurg-2020-016680
    Language: English
    Publisher: BMJ
    Publication Date: 2021
    detail.hit.zdb_id: 2506028-4
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  • 3
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    Association of intravenous thrombolysis and pre-interventional reperfusion: a post hoc analysis of the SWIFT DIRECT trial
    BMJ ; 2022
    In:  Journal of NeuroInterventional Surgery
    Details
    In: Journal of NeuroInterventional Surgery, BMJ
    Abstract: A potential benefit of intravenous thrombolysis (IVT) before mechanical thrombectomy (MT) is pre-interventional reperfusion. Currently, there are few data on the occurrence of pre-interventional reperfusion in patients randomized to IVT or no IVT before MT. Methods SWIFT DIRECT (Solitaire With the Intention For Thrombectomy Plus Intravenous t-PA vs DIRECT Solitaire Stent-retriever Thrombectomy in Acute Anterior Circulation Stroke) was a randomized controlled trial including acute ischemic stroke IVT eligible patients being directly admitted to a comprehensive stroke center, with allocation to IVT with MT versus MT alone. The primary endpoint of this analysis was the occurrence of pre-interventional reperfusion, defined as a pre-interventional expanded Thrombolysis in Cerebral Infarction score of ≥2a. The effect of IVT and potential treatment effect heterogeneity were analyzed using logistic regression analyses. Results Of 396 patients, pre-interventional reperfusion occurred in 20 (10.0%) patients randomized to IVT with MT, and in 7 (3.6%) patients randomized to MT alone. Receiving IVT favored the occurrence of pre-interventional reperfusion (adjusted OR 2.91, 95% CI 1.23 to 6.87). There was no IVT treatment effect heterogeneity on the occurrence of pre-interventional reperfusion with different strata of Randomization-to-Groin-Puncture time (p for interaction=0.33), although the effect tended to be stronger in patients with a Randomization-to-Groin-Puncture time 〉 28 min (adjusted OR 4.65, 95% CI 1.16 to 18.68). There were no significant differences in rates of functional outcomes between patients with and without pre-interventional reperfusion. Conclusion Even for patients with proximal large vessel occlusions and direct access to MT, IVT resulted in an absolute increase of 6% in rates of pre-interventional reperfusion. The influence of time strata on the occurrence of pre-interventional reperfusion should be studied further in an individual patient data meta-analysis of comparable trials. Trial registration number clinicaltrials.gov NCT03192332 .
    Type of Medium: Online Resource
    ISSN: 1759-8478 , 1759-8486
    URL: Article
    DOI: 10.1136/jnis-2022-019585
    Language: English
    Publisher: BMJ
    Publication Date: 2022
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  • 4
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    EndoVAscular treatment and ThRombolysis for Ischemic Stroke Patients (EVA-TRISP) registry: basis and methodology of a pan-European prospective ischaemic stroke revascularisation treatment registry
    BMJ ; 2021
    In:  BMJ Open Vol. 11, No. 8 ( 2021-08), p. e042211-
    Details
    In: BMJ Open, BMJ, Vol. 11, No. 8 ( 2021-08), p. e042211-
    Abstract: The Thrombolysis in Ischemic Stroke Patients (TRISP) collaboration was a concerted effort initiated in 2010 with the purpose to address relevant research questions about the effectiveness and safety of intravenous thrombolysis (IVT). The collaboration also aims to prospectively collect data on patients undergoing endovascular treatment (EVT) and hence the name of the collaboration was changed from TRISP to EVA-TRISP. The methodology of the former TRISP registry for patients treated with IVT has already been published. This paper focuses on describing the EVT part of the registry. Participants All centres committed to collecting predefined variables on consecutive patients prospectively. We aim for accuracy and completeness of the data and to adapt local databases to investigate novel research questions. Herein, we introduce the methodology of a recently constructed academic investigator-initiated open collaboration EVT registry built as an extension of an existing IVT registry in patients with acute ischaemic stroke (AIS). Findings to date Currently, the EVA-TRISP network includes 20 stroke centres with considerable expertise in EVT and maintenance of high-quality hospital-based registries. Following several successful randomised controlled trials (RCTs), many important clinical questions remain unanswered in the (EVT) field and some of them will unlikely be investigated in future RCTs. Prospective registries with high-quality data on EVT-treated patients may help answering some of these unanswered issues, especially on safety and efficacy of EVT in specific patient subgroups. Future plans This collaborative effort aims at addressing clinically important questions on safety and efficacy of EVT in conditions not covered by RCTs. The TRISP registry generated substantial novel data supporting stroke physicians in their daily decision making considering IVT candidate patients. While providing observational data on EVT in daily clinical practice, our future findings may likewise be hypothesis generating for future research as well as for quality improvement (on EVT). The collaboration welcomes participation of further centres willing to fulfill the commitment and the outlined requirements.
    Type of Medium: Online Resource
    ISSN: 2044-6055 , 2044-6055
    URL: Article
    DOI: 10.1136/bmjopen-2020-042211
    Language: English
    Publisher: BMJ
    Publication Date: 2021
    detail.hit.zdb_id: 2599832-8
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  • 5
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    Recanalisation therapies for acute ischaemic stroke in patients on direct oral anticoagulants
    BMJ ; 2021
    In:  Journal of Neurology, Neurosurgery & Psychiatry Vol. 92, No. 5 ( 2021-05), p. 534-541
    Details
    In: Journal of Neurology, Neurosurgery & Psychiatry, BMJ, Vol. 92, No. 5 ( 2021-05), p. 534-541
    Abstract: Direct oral anticoagulants (DOACs) have emerged as primary therapeutic option for stroke prevention in patients with atrial fibrillation. However, patients may have ischaemic stroke despite DOAC therapy and there is uncertainty whether those patients can safely receive intravenous thrombolysis or mechanical thrombectomy. In this review, we summarise and discuss current knowledge about different approaches to select patient. Time since last DOAC intake—as a surrogate for anticoagulant activity—is easy to use but limited by interindividual variability of drug pharmacokinetics and long cut-offs ( 〉 48 hours). Measuring anticoagulant activity using drug-specific coagulation assays showed promising safety results. Large proportion of patients at low anticoagulant activity seem to be potentially treatable but there remains uncertainty about exact safe cut-off values and limited assay availability. The use of specific reversal agents (ie, idarucizumab or andexanet alfa) prior to thrombolysis is a new emerging option with first data reporting safety but issues including health economics need to be elucidated. Mechanical thrombectomy appears to be safe without any specific selection criteria applied. In patients on DOAC therapy with large vessel occlusion, decision for intravenous thrombolysis should not delay thrombectomy (eg, direct thrombectomy or immediate transfer to a thrombectomy-capable centre recommended). Precision medicine using a tailored approach combining clinicoradiological information (ie, penumbra and vessel status), anticoagulant activity and use of specific reversal agents only if necessary seems a reasonable choice.
    Type of Medium: Online Resource
    ISSN: 0022-3050 , 1468-330X
    URL: Article
    DOI: 10.1136/jnnp-2020-325456
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    Language: English
    Publisher: BMJ
    Publication Date: 2021
    detail.hit.zdb_id: 1480429-3
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  • 6
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    Impact of time to endovascular reperfusion on outcome differs according to the involvement of the proximal MCA territory
    BMJ ; 2018
    In:  Journal of NeuroInterventional Surgery Vol. 10, No. 6 ( 2018-06), p. 530-536
    Details
    In: Journal of NeuroInterventional Surgery, BMJ, Vol. 10, No. 6 ( 2018-06), p. 530-536
    Abstract: The time interval between symptom onset and reperfusion is a major determinant of the benefit of endovascular therapy (ET) and patients’ outcome. The impact of time may be attenuated in patients with robust collaterals. However, not all regions in the middle cerebral artery (MCA) territory have access to collaterals. Purpose To evaluate if the involvement of the poorly collateralized proximal MCA territory has an impact on the degree of time dependency of patients’ outcome. Methods Patients with MCA occlusions treated with ET and involvement/sparing of the proximal striatocapsular MCA territory (SC+/SC−, each n=97) were matched according to their symptom onset to reperfusion times (SORTs). Correlation and impact of time on outcome was evaluated with strata of SC+/SC− using multivariate logistic regression models (LRMs), including interaction terms. Discharge National Institute of Health Stroke Scale (NIHSS-DIS) score 〈 5 and discharge modified Rankin Scale (mRS-DIS) score ≤2 were prespecified outcome measures. Results A stronger correlation between all outcome measures (NIHSS-DIS/ΔNIHSS/mRS-DIS) and SORTs was found for SC+ patients than for SC−patients. SORTs were significant variables in LRMs for mRS-DIS score ≤2 and NIHSS-DIS score 〈 5 in SC+ but not in SC− patients. Interaction of SC+ and SORTs was significant in LRMs for both endpoints. Conclusion Time dependency of outcome after ET is more pronounced if parts of the proximal MCA territory are affected. This may reflect the lack of collateralization in the striatocapsular region and a more stringent cell death with time. If confirmed, this finding may affect the selection of patients based on different time windows according to the territory at risk.
    Type of Medium: Online Resource
    ISSN: 1759-8478 , 1759-8486
    URL: Article
    URL: Article
    DOI: 10.1136/neurintsurg-2017-013319
    DOI: 10.1136/neurintsurg-2017-013319.supp1
    Language: English
    Publisher: BMJ
    Publication Date: 2018
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  • 7
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    Incidence and outcome of perforations during medium vessel occlusion compared with large vessel occlusion thrombectomy
    BMJ ; 2023
    In:  Journal of NeuroInterventional Surgery
    Details
    In: Journal of NeuroInterventional Surgery, BMJ
    Abstract: Vessel perforation during thrombectomy is a severe complication and is hypothesized to be more frequent during medium vessel occlusion (MeVO) thrombectomy. The aim of this study was to compare the incidence and outcome of patients with perforation during MeVO and large vessel occlusion (LVO) thrombectomy and to report on the procedural steps that led to perforation. Methods In this multicenter retrospective cohort study, data of consecutive patients with vessel perforation during thrombectomy between January 1, 2015 and September 30, 2022 were collected. The primary outcomes were independent functional outcome (ie, modified Rankin Scale 0–2) and all-cause mortality at 90 days. Binomial test, chi-squared test and t -test for unpaired samples were used for statistical analysis. Results During 25 769 thrombectomies (5124 MeVO, 20 645 LVO) in 25 stroke centers, perforation occurred in 335 patients (1.3%; mean age 72 years, 62% female). Perforation occurred more often in MeVO thrombectomy (2.4%) than in LVO thrombectomy (1.0%, p 〈 0.001). More MeVO than LVO patients with perforation achieved functional independence at 3 months (25.7% vs 10.9%, p =0.001). All-cause mortality did not differ between groups (overall 51.6%). Navigation beyond the occlusion and retraction of stent retriever/aspiration catheter were the two most common procedural steps that led to perforation. Conclusions In our cohort, perforation was approximately twice as frequent in MeVO than in LVO thrombectomy. Efforts to optimize the procedure may focus on navigation beyond the occlusion site and retraction of stent retriever/aspiration catheter. Further research is necessary in order to identify thrombectomy candidates at high risk of intraprocedural perforation and to provide data on the effectiveness of endovascular countermeasures.
    Type of Medium: Online Resource
    ISSN: 1759-8478 , 1759-8486
    URL: Article
    DOI: 10.1136/jnis-2023-020531
    Language: English
    Publisher: BMJ
    Publication Date: 2023
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  • 8
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    Direct mechanical thrombectomy in tPA-ineligible and -eligible patients versus the bridging approach: a meta-analysis
    BMJ ; 2019
    In:  Journal of NeuroInterventional Surgery Vol. 11, No. 1 ( 2019-01), p. 20-27
    Details
    In: Journal of NeuroInterventional Surgery, BMJ, Vol. 11, No. 1 ( 2019-01), p. 20-27
    Abstract: Whether pretreatment with intravenous thrombolysis prior to mechanical thrombectomy (IVT+MTE) adds additional benefit over direct mechanical thrombectomy (dMTE) in patients with large vessel occlusions (LVO) is a matter of debate. Methods This study-level meta-analysis was presented in accord with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Pooled effect sizes were calculated using the inverse variance heterogeneity model and displayed as summary Odds Ratio (sOR) and corresponding 95% confidence interval (95% CI). Sensitivity analysis was performed by distinguishing between studies including dMTE patients eligible for IVT (IVT-E) or ineligible for IVT (IVT-IN). Primary outcome measures were functional independence (modified Rankin Scale≤2) and mortality at day 90, successful reperfusion, and symptomatic intracerebral hemorrhage. Results Twenty studies, incorporating 5279 patients, were included. There was no evidence that rates of successful reperfusion differed in dMTE and IVT+MTE patients (sOR 0.93, 95% CI 0.68 to 1.28). In studies including IVT-IN dMTE patients, patients undergoing dMTE tended to have lower rates of functional independence and had higher odds for a fatal outcome as compared with IVT+MTE patients (sOR 0.78, 95% CI 0.61 to 1.01 and sOR 1.45, 95% CI 1.22 to 1.73). However, no such treatment group effect was found when analyses were confined to cohorts with a lower risk of selection bias (including IVT-E dMTE patients). Conclusion The quality of evidence regarding the relative merits of IVT+MTE versus dMTE is low. When considering studies with lower selection bias, the data suggest that dMTE may offer comparable safety and efficacy as compared with IVT+MTE. The conduct of randomized-controlled clinical trials seems justified.
    Type of Medium: Online Resource
    ISSN: 1759-8478 , 1759-8486
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.1136/neurintsurg-2018-013834
    DOI: 10.1136/neurintsurg-2018-013834.supp1
    DOI: 10.1136/neurintsurg-2018-013834.supp2
    Language: English
    Publisher: BMJ
    Publication Date: 2019
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  • 9
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    Perceived acceptable uncertainty regarding comparability of endovascular treatment alone versus intravenous thrombolysis plus endovascular treatment
    BMJ ; 2023
    In:  Journal of NeuroInterventional Surgery Vol. 15, No. 3 ( 2023-03), p. 227-232
    Details
    In: Journal of NeuroInterventional Surgery, BMJ, Vol. 15, No. 3 ( 2023-03), p. 227-232
    Abstract: Most trials comparing endovascular treatment (EVT) alone versus intravenous thrombolysis with alteplase (IVT) + EVT in directly admitted patients with a stroke are non-inferiority trials. However, the margin based on the level of uncertainty regarding non-inferiority of the experimental treatment that clinicians are willing to accept to incorporate EVT alone into clinical practice remains unknown. Objective To characterize what experienced stroke clinicians would consider an acceptable level of uncertainty for hypothetical decisions on whether to administer IVT or not before EVT in patients admitted directly to EVT-capable centers. Methods A web-based, structured survey was distributed to a cross-section of 600 academic neurologists/neurointerventionalists. For this purpose, a response framework for a hypothetical trial comparing IVT+EVT (standard of care) with EVT alone (experimental arm) was designed. In this trial, a similar proportion of patients in each arm achieved functional independence at 90 days. Invited physicians were asked at what level of certainty they would feel comfortable skipping IVT in clinical practice, considering these hypothetical trial results. Results There were 180 respondents (response rate: 30%) and 165 with complete answers. The median chosen acceptable uncertainty suggesting reasonable comparability between both treatments was an absolute difference in the rate of day 90 functional independence of 3% (mode 5%, IQR 1–5%), with higher chosen margins observed in interventionalists (aOR 2.20, 95% CI 1.06 to 4.67). Conclusion Physicians would generally feel comfortable skipping IVT before EVT at different certainty thresholds. Most physicians would treat with EVT alone if randomized trial data suggested that the number of patients achieving functional independence at 90 days was similar between the two groups, and one could be sufficiently sure that no more than 3 out of 100 patients would not achieve functional independence at 90 days due to skipping IVT.
    Type of Medium: Online Resource
    ISSN: 1759-8478 , 1759-8486
    URL: Article
    DOI: 10.1136/neurintsurg-2022-018665
    Language: English
    Publisher: BMJ
    Publication Date: 2023
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  • 10
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    Interaction between intravenous thrombolysis and clinical outcome between slow and fast progressors undergoing mechanical thrombectomy: a post-hoc analysis of the SWIFT-DIRECT trial
    BMJ ; 2023
    In:  Journal of NeuroInterventional Surgery
    Details
    In: Journal of NeuroInterventional Surgery, BMJ
    Abstract: In proximal occlusions, the effect of reperfusion therapies may differ between slow or fast progressors. We investigated the effect of intravenous thrombolysis (IVT) (with alteplase) plus mechanical thrombectomy (MT) versus thrombectomy alone among slow versus fast stroke progressors. Methods The SWIFT-DIRECT trial data were analyzed: 408 patients randomized to IVT+MT or MT alone. Infarct growth speed was defined by the number of points of decay in the initial Alberta Stroke Program Early CT Score (ASPECTS) divided by the onset-to-imaging time. The primary endpoint was 3-month functional independence (modified Rankin scale 0–2). In the primary analysis, the study population was dichotomized into slow and fast progressors using median infarct growth velocity. Secondary analysis was also conducted using quartiles of ASPECTS decay. Results We included 376 patients: 191 IVT+MT, 185 MT alone; median age 73 years (IQR 65–81); median initial National Institutes of Health Stroke Scale (NIHSS) 17 (IQR 13–20). The median infarct growth velocity was 1.2 points/hour. Overall, we did not observe a significant interaction between the infarct growth speed and the allocation to either randomization group on the odds of favourable outcome (P=0.68). In the IVT+MT group, odds of any intracranial hemorrhage (ICH) were significantly lower in slow progressors (22.8% vs 36.4%; OR 0.52, 95% CI 0.27 to 0.98) and higher among fast progressors (49.4% vs 26.8%; OR 2.62, 95% CI 1.42 to 4.82) (P value for interaction 〈 0.001). Similar results were observed in secondary analyses. Conclusion In this SWIFT-DIRECT subanalysis, we did not find evidence for a significant interaction of the velocity of infarct growth on the odds of favourable outcome according to treatment by MT alone or combined IVT+MT. However, prior IVT was associated with significantly reduced occurrence of any ICH among slow progressors whereas this was increased in fast progressors.
    Type of Medium: Online Resource
    ISSN: 1759-8478 , 1759-8486
    URL: Article
    DOI: 10.1136/jnis-2023-020113
    Language: English
    Publisher: BMJ
    Publication Date: 2023
    detail.hit.zdb_id: 2506028-4
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