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Meta-Analysis
. 2024 Jan;19(1):58-67.
doi: 10.1177/17474930231180434. Epub 2023 Jun 8.

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

Adnan Mujanovic  1 , Felix Ng  2   3 , Thomas R Meinel  4 , Tomas Dobrocky  1 , Eike I Piechowiak  1 , Christoph C Kurmann  1   5 , David J Seiffge  4 , Susanne Wegener  6 , Roland Wiest  1 , Lukas Meyer  7 , Jens Fiehler  7 , Jean Marc Olivot  8 , Marc Ribo  9 , Thanh N Nguyen  10 , Jan Gralla  1 , Bruce Cv Campbell  2 , Urs Fischer  4   11 , Johannes Kaesmacher  1
Affiliations
Meta-Analysis

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

Adnan Mujanovic et al. Int J Stroke. 2024 Jan.

Abstract

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.

Keywords: No-reflow; macrovascular; microvascular; perfusion imaging; reperfusion.

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Conflict of interest statement

Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: TD reports consultancy for Medtronic. JMO reports consultancy for Bioxodes, Abbvie, and Acticor, and speaker fees from Boehringer Ingelheim and Bristol Myers Squibb. JG reports a Swiss National Funds grant for MRI in stroke. UF reports research grants from Medtronic BEYOND SWIFT registry, the Swiss National Science Foundation, and the Swiss Heart Foundation; consulting fees from Medtronic, Stryker, and CSL Behring (fees paid to institution); has membership of a data safety monitoring board for the IN EXTREMIS trial and the TITAN trial; and was on the advisory board for Portola (Alexion; fees paid to institution). JK reports financial support from Medtronic for the BEYOND SWIFT registry (fees paid to institution); and research grants from the Swiss National Science Foundation supporting the TECNO trial (fees paid to institution), Swiss Academy of Medical Sciences supporting MRI research (fees paid to institution), and Swiss Heart Foundation supporting cardiac MRI in the aetiological work-up of stroke patients (fees paid to institution).

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