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

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.

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.

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).

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.