Endovascular treatment in anterior circulation stroke beyond 6.5 hours after onset or time last seen well: results from the MR CLEAN Registry

Abstract

BackgroundRandomised controlled trials with perfusion selection have shown benefit of endovascular treatment (EVT) for ischaemic stroke between 6 and 24 hours after symptom onset or time last seen well. However, outcomes after EVT in these late window patients without perfusion imaging are largely unknown. We assessed their characteristics and outcomes in routine clinical practice.MethodsThe Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands Registry, a prospective, multicentre study in the Netherlands, included patients with an anterior circulation occlusion who underwent EVT between 2014 and 2017. CT perfusion was no standard imaging modality. We used adjusted ordinal logistic regression analysis to compare patients treated within versus beyond 6.5 hours after propensity score matching on age, prestroke modified Rankin Scale (mRS), National Institutes of Health Stroke Scale, Alberta Stroke Programme Early CT Score (ASPECTS), collateral status, location of occlusion and treatment with intravenous thrombolysis. Outcomes included 3-month mRS score, functional independence (defined as mRS 0–2), and death.ResultsOf 3264 patients who underwent EVT, 106 (3.2%) were treated beyond 6.5 hours (median 8.5, IQR 6.9–10.6), of whom 93 (87.7%) had unknown time of stroke onset. CT perfusion was not performed in 87/106 (80.2%) late window patients. Late window patients were younger (mean 67 vs 70 years, p<0.04) and had slightly lower ASPECTS (median 8 vs 9, p<0.01), but better collateral status (collateral score 2–3: 68.3% vs 57.7%, p=0.03). No differences were observed in proportions of functional independence (43.3% vs 40.5%, p=0.57) or death (24.0% vs 28.9%, p=0.28). After matching, outcomes remained similar (adjusted common OR for 1 point improvement in mRS 1.04, 95% CI 0.56 to 1.93).ConclusionsWithout the use of CT perfusion selection criteria, EVT in the 6.5–24-hour time window was not associated with poorer outcome in selected patients with favourable clinical and CT/CT angiography characteristics. randomised controlled trials with lenient inclusion criteria are needed to identify more patients who can benefit from EVT in the late window.

Endovascular thrombectomy for anterior circulation stroke beyond 6 hours of onset in Sweden 2015 to 2020: rates and outcomes in a nationwide register-based study

“…Our results show that treatment outcomes in nationwide routine clinical practice are well in keeping with the RCTs7 8 as well as the recent individual-level data AURORA (Analysis of Pooled Data from Randomized Studies of Thrombectomy More Than 6 Hours After Last Known Well) meta-analysis 19. The rate of functional independence in the AURORA meta-analysis EVT arm was 45.9%,19 while the corresponding rates in observational studies ranged from 24.5–62% 20–27. One recently published study on 53 702 EVTs in US clinical practice reported an equal proportion of late window EVTs (33%) to our nationwide material,28 while two other comparable studies presented lower proportions of late window treatments (10.7–11%) 20 22.…”

Stroke imaging modality for endovascular therapy in the extended window: systematic review and meta-analysis

“…In a post hoc analysis of one registry,12 patients treated in the extended time window had similar rates of functional independence using CTP or NCCT (54.7% vs 60.6%). Several observational and registry studies11–17 35 showed similar results, but with the limitation of an indirect comparison between imaging modality, since their main objective was to compare the early versus extended time window or EVT versus best medical treatment.…”

“…It is unclear whether an approach to the extended window EVT that does not use ADVI would be equivalent to the current guidelines recommended strategy. Current evidence from cohort studies report conflicting results, with several studies suggesting superiority of ADVI,9 10 while others showed a similar proportion of functional independence without ADVI 9–17. Furthermore, no RCT compared these two approaches for patient selection during the extended time window in patients with anterior circulation LVO.…”

Association between time to treatment and clinical outcomes in endovascular thrombectomy beyond 6 hours without advanced imaging selection

“…Previous observational studies assessing overall rates of functional independence (mRS ≤2) in the late EVT window have reported different results at 90-day follow-up, ranging from 20% to 64% using various pre-specified clinical and imaging patient selection criteria 8–11 18 20–23. Some of these investigations incorporated perfusion-based imaging with varying adherence to the DAWN and DEFUSE-3 eligibility criteria,18 20–23 while others used solely NCCT and CTA, but also varied in their selection criteria 8–11.…”

“…Ongoing RCTs are assessing whether treatment benefit with EVT is maintained in patients presenting beyond 6 hours of stroke onset when less restrictive clinical and imaging selection criteria are used 6 7. In the interim, functional and safety outcome data following EVT in the absence of CT perfusion or MR imaging in the late window is limited 8–11. Furthermore, while functional outcomes are highly time sensitive to EVT in the early (<6 hours) window, studies have reported a transition to a slower loss of effectiveness from EVT in the late window 12 13.…”