Thrombectomy in addition to thrombolysis for medium distal vessel occlusions - results from the SITS registry

Background Endovascular thrombectomy (EVT) is standard of care for acute ischemic stroke (AIS) caused by large vessel occlusion. Medium distal vessel occlusions (MDVO) account for 25-40% AIS cases, but recanalization rates with intravenous thrombolysis (IVT) are often below 50%. Studies have shown mixed results comparing EVT with best medical management in different MDVO populations. This study aims to show if EVT in addition to IVT is associated with clinical benefits or harm in patients with MDVO.

We performed an observational study of patients in the Safe Implementation of Treatments of Stroke International Stroke Registry (SITS-ISTR) 2016–23, treated with IVT or IVT+EVT for occlusion of the ACA, PCA or distal MCA (M3 and more distal). Outcomes were modified Rankin Scale score (mRS), death at 3 months, and post-treatment hemorrhage. Inverse probability treatment weighting and binomial logistic regression was performed due to baseline imbalances (age, NIHSS and occlusion site).

Of 2198 included patients, 1903 (87%) received IVT, and 295 (13%) IVT+EVT. IVT+EVT patients were younger (73 vs 75) and had higher median NIHSS: 10 (IQR 6-15) vs 8 (5-12), p<0.001. The most common occlusion site was PCA in the IVT+EVT group, (n=179, 60.7%), and distal MCA (n=1140, 59.9%) in the IVT group. Rates of symptomatic intracerebral hemorrhage (SICH) were higher in the IVT+EVT group (SICH NINDS: 7.6% vs 3.5%, p=0.003; SICH ECASS-II: 5.4% vs 2.4%, p=0.011). After adjustment, IVT+EVT was associated with worse outcomes compared to IVT alone (aOR, 95% CI); mRS 0-1: 0.63 (0.44-0.90), mRS 0-2: 0.64 (0.44-0.91) and death: 2.03 (1.26-3.27).

IVT+EVT for MDVO was associated with worse outcomes compared to IVT alone. Results should be interpreted with caution due to retrospective observational design, warranting further randomized studies, but are in line with recently published RCTs Competing Interest Statement The authors have declared no competing interest. Funding Statement Funding: Author BK received support from the Swedish Stroke Association (Strokeförbundet) for analysis and writing of the manuscript. SITS-ISTR is financed directly and indirectly by grants from Karolinska Institutet, Stockholm County Council, the Swedish Heart-Lung Foundation, as well as from an unrestricted sponsorship from Boehringer-Ingelheim. SITS is currently conducting studies supported by Boehringer-Ingelheim and Astra Zeneca. SITS has previously received grants from the European Union Framework 7, the European Union Public Health Authority, Ferrer International, EVER Pharma and Biogen and conducted study in collaboration with Karolinska Institutet, supported by Stryker, Covidien and Phenox. Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethics approval was obtained from the Stockholm Regional Ethics Committee for this project as part of the SITS-MOST (Safe Implementation of Thrombolysis in Stroke Monitoring Study) II framework. The SITS International Coordination Office monitored the SITS-ISTR data online and checked individual patient data monthly to identify errors or inconsistencies. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data Availability The corresponding author had full access to the data in the study and takes full responsibility for its integrity and the data analysis. Access to the anonymized data for this study will be available from the corresponding author upon reasonable request from qualified researchers, contingent on approval by the SITS Scientific Committee.