No-reflow phenomenon in stroke patients: A systematic literature review and meta-analysis of clinical data

Background: The no-reflow phenomenon refers to the absence of microvascular reperfusion despite macrovascular reperfusion. Aim: The aim of this analysis was to summarize the available clinical evidence on no-reflow in patients with acute ischemic stroke. Methods: A systematic literature review and a meta-analysis of clinical data on definition, rates, and impact of the no-reflow phenomenon after reperfusion therapy was carried out. A predefined research strategy was formulated according to the Population, Intervention, Comparison, and Outcome (PICO) model and was used to screen for articles in PubMed, MEDLINE, and Embase up to 8 September 2022. Whenever possible, quantitative data were summarized using a random-effects model. Results: Thirteen studies with a total of 719 patients were included in the final analysis. Most studies (n = 10/13) used variations of the Thrombolysis in Cerebral Infarction scale to evaluate macrovascular reperfusion, whereas microvascular reperfusion and no-reflow were mostly assessed on perfusion maps (n = 9/13). In one-third of stroke patients with successful macrovascular reperfusion (29%, 95% confidence interval (CI), 21-37%), the no-reflow phenomenon was observed. Pooled analysis showed that no-reflow was consistently associated with reduced rates of functional independence (odds ratio (OR), 0.21, 95% CI, 0.15-0.31). Conclusion: The definition of no-reflow varied substantially across studies, but it appears to be a common phenomenon. Some of the no-reflow cases may simply represent remaining vessel occlusions, and it remains unclear whether no-reflow is an epiphenomenon of the infarcted parenchyma or causes infarction. Future studies should focus on standardizing the definition of no-reflow with more consistent definitions of successful macrovascular reperfusion and experimental set-ups that could detect the causality of the observed findings.

Automated summary

This study conducted a systematic literature review and meta-analysis to summarize the clinical evidence on the no-reflow phenomenon in patients with acute ischemic stroke. The results showed that one-third of stroke patients (29%) experienced no-reflow after successful macrovascular reperfusion, and no-reflow was consistently associated with reduced rates of functional independence. However, there were variations in the definition of no-reflow, and further research is needed to standardize its definition and explore its causality with stroke.