Persistent Tissue-Level Hypoperfusion (No-Reflow) Negates the Clinical Benefit of Successful Thrombectomy

BACKGROUND: Tissue-level hypoperfusion (no-reflow) persists in 30% of patients with seemingly successful upstream angiographic recanalization at thrombectomy. We investigated the clinical impact of the no-reflow phenomenon by comparing patients with no-reflow versus patients with varying degrees of angiographic recanalization. METHODS: In a post hoc pooled analysis of the EXTEND-IA (Endovascular Therapy for Ischemic Stroke With Perfusion-Imaging Selection) and EXTEND-IA TNK (Tenecteplase Versus Alteplase Before Thrombectomy for Ischemic Stroke) part 1 and 2 trials, clinical and radiological outcomes were compared between patients with (1) full angiographic recanalization with no-reflow (extended Thrombolysis in Cerebral Infarction [eTICI] 2c3–NoReflow), defined as >15% reduction in relative cerebral blood flow or Volume within the infarct relative to a contralateral homolog on 24-hour-follow-up perfusion computed tomography or magnetic resonance imaging despite eTICI grade 2c-3 angiographic recanalization, (2) full angiographic recanalization and tissue reperfusion (eTICI 2c3–CompleteFlow), (3) partial angiographic recanalization (eTICI 2b), and (4) unsuccessful thrombectomy (eTICI 0-2a). The primary outcome, functional independence at 90 days, was investigated using a mixed effect logistic regression model, both unadjusted and adjusted for a priori-selected covariates, namely age, premorbid modified Rankin Scale, baseline National Institutes of Health Stroke Scale, and baseline core volume. RESULTS: Among 537 patients from the overall pooled cohort, 456 patients were included in the analysis. The mean age of the included patients was 71 years old, and 54% were male. A favorable outcome (90-day modified Rankin Scale score of 0–2 or return to baseline modified Rankin Scale) was observed in 43.33% (n=13/30) of patients with eTICI 2c3–NoReflow, 67.50% (n=81/120) of eTICI 2c3–CompleteFlow, 63.03% (n=150/238) of eTICI 2b, and 50.00% (n=34/68) of unsuccessful thrombectomy. In multivariable analysis, patients with eTICI 2c3–NoReflow had lower odds of favorable outcome compared with those with eTICI 2c3–CompleteFlow (adjusted odds ratio, 0.31 [95% CI, 0.12–0.77]; P =0.01) and eTICI 2b (adjusted odds ratio, 0.40 [95% CI, 0.17–0.96]; P =0.04) but not unsuccessful thrombectomy (adjusted odds ratio, 1.02 [95% CI, 0.38–2.73]; P =0.97). Patients with eTICI 2c3–NoReflow had similar follow-up infarct volume to unsuccessful thrombectomy ( β =−8.26 [95% CI, −27.38 to 10.86]; P =0.40) and eTICI 2b ( β =9.38 [95% CI, −7.33 to 26.09]; P =0.27) but had larger infarcts compared with eTICI 2c3–CompleteFlow ( β =18.85 [95% CI, 1.16–36.54]; P =0.04). CONCLUSIONS: When no-reflow occurred, clinical and radiological outcomes in patients with full angiographic recanalization were similar to patients with unsuccessful thrombectomy. Preventing or reversing no-reflow has the potential to augment the clinical benefit of reperfusion treatment in ischemic stroke.