Association between the no-reflow phenomenon and clinical outcomes after endovascular treatment for acute ischemic stroke: A systematic review and meta-analysis

Abstract Background The no-reflow phenomenon, characterized by impaired microvascular reperfusion despite successful macrovascular recanalization, has been identified as a potential contributor to poor outcomes in acute ischemic stroke (AIS) treated with endovascular therapy (EVT). This systematic review and meta-analysis aimed to assess the prevalence and clinical impact of no-reflow phenomenon in AIS patients undergoing EVT. Methods We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) and observational studies reporting the no-reflow phenomenon after EVT. Databases searched included PubMed, Embase, and CENTRAL (inception to February 9, 2025). Outcomes included no-reflow prevalence, functional outcomes (mRS), early neurological recovery, infarct volume, hemorrhagic complications, and 90-day mortality. Pooled risk ratios (RR) or mean differences (MD) were calculated using random-effects meta-analysis, and heterogeneity was assessed with I2. Results Eight studies (n = 1483 patients) were included. The pooled prevalence of no-reflow was 20.5% (95% CI 6.2%–49.9%; I2 = 96.9%). Compared with controls, patients with no-reflow had reduced early neurological recovery (RR 0.76; 95% CI 0.64–0.90) and increased risk of hemorrhagic transformation (RR 1.82; 95% CI 1.18–2.79) and symptomatic intracranial hemorrhage (RR 1.88; 95% CI 1.00–3.56). Differences in functional independence (mRS 0–2) and mortality were not statistically significant. Subgroup analyses based on study design revealed divergent patterns, particularly for infarct volume, which was significantly greater in no-reflow patients in post-hoc RCTs but not in the overall analysis. Conclusion No-reflow affects one in five EVT-treated patients and is associated with adverse neurological and hemorrhagic outcomes. Findings highlight the need for standardized definitions and prospective trials to clarify its clinical impact.