ArticlesPenumbral imaging and functional outcome in patients with anterior circulation ischaemic stroke treated with endovascular thrombectomy versus medical therapy: a meta-analysis of individual patient-level data
Introduction
Endovascular thrombectomy substantially reduces disability in patients with ischaemic stroke due to large vessel occlusion.1 The optimal selection of patients to identify all those who might benefit from this procedure is a key clinical question. A meta-analysis of individual-patient data on endovascular thrombectomy after large-vessel ischaemic stroke showed remarkable consistency in treatment effect across clinical subgroups, although age and clinical severity remained strongly prognostic1 and treatment effect declined with delayed reperfusion.2 Brain imaging is a key prognostic biomarker in stroke patients. The positive trials of endovascular thrombectomy at 0–6 h after ischaemic stroke onset have used different brain imaging selection criteria and the optimal approach to identifying patients who might benefit from thrombectomy using imaging has remained uncertain.3, 4, 5, 6, 7, 8, 9
Imaging selection for ischaemic stroke treatment aims to identify individual pathophysiology, rather than using traditional group-average time thresholds.10 The presence of ischaemic penumbra (electrically non-functioning but metabolically viable brain tissue that is salvageable with rapid cerebral blood flow restoration) forms the rationale for reperfusion therapies. Patients have marked variation in collateral blood flow (via leptomeningeal anastomoses and other pathways) that maintains penumbra distal to an arterial occlusion.11, 12 Penumbral imaging with CT perfusion (CTP) or MRI, when processed in a reproducible manner using validated blood flow parameter thresholds, can estimate both the irreversibly injured ischaemic core and potentially salvageable ischaemic penumbra with reasonable accuracy in the individual patient.13, 14, 15, 16 The difference in volume between the critically hypoperfused tissue (or territory of the occluded artery) and the ischaemic core estimates the salvageable penumbra.
The DAWN17 and DEFUSE 318 trials showed a benefit of endovascular thrombectomy beyond 6 h after stroke in patients with favourable penumbral patterns on CTP or MRI. However, the role of penumbral imaging selection within 6 h of stroke onset remains unclear. Patients with a large estimated ischaemic core (eg, ≥70 mL) are sometimes excluded from reperfusion therapies4, 5, 6, 7 and the positive trials of endovascular thrombectomy have used variable non-contrast CT, CT angiographic collaterals, CTP, and MRI criteria to select patients. Data characterising the clinical benefit of endovascular thrombectomy as ischaemic core volume increases are scarce. The DEFUSE 2 prospective cohort study showed benefit of endovascular reperfusion in patients with favourable perfusion and diffusion MRI (criteria included diffusion MRI lesion volume of <70 mL), while patients without the favourable imaging profile did not benefit.12 By contrast, two retrospective observational studies suggested a benefit of reperfusion in patients with a diffusion MRI lesion volume of at least 70 mL19 or Alberta Stroke Program Early CT Score (ASPECTS) less than 6, which indicates a large ischaemic core.20 Furthermore, subanalysis of pretreatment CTP in 175 patients in MR CLEAN21 found no interaction between ischaemic core volume and treatment effect.
We did a systematic review and meta-analysis of all randomised controlled trials of stent-retriever thrombectomy versus medical therapy within 6 h of stroke to assess the influence of ischaemic core volume and mismatch volume on functional outcome after thrombectomy.
Section snippets
Search strategy and selection criteria
In this systematic review and meta-analysis, we assessed endovascular thrombectomy predominantly performed with stent retrievers versus medical therapy in patients with anterior circulation ischaemic stroke, according to PRISMA guidelines. We searched PubMed for randomised controlled trials published in any language between Jan 1, 2010, and May 31, 2017, using the search string ((“randomised controlled trial” [Publication Type]) AND ((thrombectomy[Title/Abstract]) OR (clot
Results
Seven studies were identified in PubMed, and all were included in the systematic review and meta-analysis (appendix). Of 1764 patients included in the seven randomised controlled trials, penumbral imaging was performed and assessable in 900 (51%). CTP was obtained in 625 (35%) of the 1764 patients, and 34 of these patients were excluded (11 severe motion artefacts, seven no lesion within coverage, two contrast bolus failure, and 14 because of data corruption during transfer from site). Of the
Discussion
Large estimated ischaemic core volume was independently associated with worse functional outcome in patients treated with endovascular thrombectomy and in those who received standard medical therapy. Every 10 mL increase in pretreatment ischaemic core volume reduced the odds of favourable functional outcomes by 20–30%. However, large ischaemic core volume did not prevent benefit of endovascular thrombectomy compared with standard medical therapy in patients who otherwise met eligibility for
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