Translating large-core thrombectomy evidence into clinical practice

Recent randomized trials have rapidly expanded the evidence base for endovascular thrombectomy (EVT) in acute ischemic stroke with a large ischemic core, including RESCUE-Japan LIMIT, ANGEL-ASPECT, SELECT2, TENSION, LASTE, and TESLA (1-6). Among these trials, TENSION and its extended follow-up provided particularly important insights into the pragmatic implementation of thrombectomy in routine clinical practice (4,7). Unlike SELECT2 and ANGEL-ASPECT, which largely incorporated advanced perfusion imaging and ischemic core-volume estimation (2,3), TENSION primarily relied on non-contrast computed tomography (NCCT) Alberta Stroke Program Early CT Score (ASPECTS)-based selection criteria (4). This simplified imaging paradigm is clinically meaningful because advanced perfusion imaging may not be universally available and may also introduce additional workflow complexity and treatment delay in time-sensitive settings. In many stroke centers, particularly during off-hours or in resource-limited environments, immediate access to perfusion imaging and automated post-processing software may be limited, potentially delaying reperfusion therapy in patients with rapidly evolving infarction. In addition, multimodal imaging may increase workflow complexity and add contrast exposure, which may be relevant in selected patients with renal vulnerability or multiple comorbidities. By demonstrating improved functional outcomes and lower mortality in a trial that used a more accessible imaging-selection strategy, TENSION suggested that EVT decision-making in large-core stroke may be simplified without mandatory reliance on sophisticated imaging-based core quantification, thereby broadening the applicability and timeliness of reperfusion therapy in routine clinical practice (4). This assumption was directly tested by a recent study that applied TENSION’s eligibility criteria to a comparable German Stroke Registry cohort, providing empirical support for the replicability of TENSION’s functional outcomes in routine clinical practice (8). Importantly, these findings were observed in an older and clinically severe population rather than in selectively milder patients.

An important distinction, however, is that TENSION, although allowing enrollment up to 12 hours from stroke onset, largely represented a relatively early-window large-core population. The median time from symptom onset to groin puncture in TENSION was 4.2 hours, whereas SELECT2 enrolled patients at a median of 9.31 hours from last known well time and ANGEL-ASPECT reported a median onset-to-randomization time of 456 minutes, with only approximately 36% of patients treated within 6 hours (2-4). This difference may be clinically relevant because infarct evolution and tissue viability become increasingly heterogeneous over time, potentially increasing the importance of advanced tissue characterization in the late-window setting. Accordingly, although TENSION supports the feasibility of pragmatic NCCT-ASPECTS-based decision-making in relatively early large-core stroke, it remains uncertain whether similarly simplified selection strategies can be safely generalized to patients presenting beyond 12 hours from onset.

However, neither TENSION nor most prior large-core EVT trials demonstrated a clear reduction in the need for decompressive craniectomy despite improved survival with EVT (1-6). Consistent with these findings, a recent meta-analysis of five randomized controlled trials showed no statistically significant difference in the rate of decompressive craniectomy between the EVT plus medical therapy and medical therapy alone groups [risk ratio (RR) 1.23; 95% confidence interval (CI): 0.90–1.68; P=0.20; I2=10%] (9). This discrepancy may partly reflect the fact that decompressive surgery is influenced not only by edema severity, but also by patient age, premorbid functional status, family preferences, and institutional practice patterns (10,11). In addition, reperfusion may improve survival without completely preventing malignant edema in patients with already extensive irreversible infarction. One possible explanation is that reperfusion attenuates the severity and duration of secondary injury after infarction, even when decompressive craniectomy remains necessary. Compared with non-reperfused tissue, reperfused brain tissue may exhibit less ongoing infarct progression, reduced peri-infarct edema evolution, and greater physiological stability following decompressive surgery, thereby contributing to improved survival despite similar rates of craniectomy.

These findings suggest that the therapeutic concept of EVT in large-core stroke may differ fundamentally from that in smaller infarcts. Unlike perfusion-core mismatch paradigms that primarily aim to identify and salvage substantial volumes of viable tissue to restore functional independence (12,13), EVT in large-core infarction may instead function by attenuating infarct progression, limiting secondary injury and edema formation, and preventing progression toward fatal ischemic stroke. In TENSION, 90-day mortality was lower in the EVT group than in the medical-treatment group, 40% versus 51%, respectively, but death or dependency remained frequent, affecting approximately 69% of EVT-treated patients at 90 days (4). Accordingly, the clinical benefit of reperfusion in this population may be better understood as mitigation of catastrophic neurological injury rather than restoration of complete neurological recovery.

Accordingly, EVT in large-core stroke should not be viewed simply as a routine reperfusion procedure, but rather as a complex life-saving intervention requiring careful shared decision-making with patients, surrogate decision-makers, and families. Realistic discussions regarding the substantial risks of death and survival with severe long-term disability remain essential even after technically successful reperfusion. These considerations further suggest that outcome optimization in large-core stroke may increasingly depend not only on reperfusion itself, but also on subsequent post-EVT neurocritical care and secondary injury management.

The persistently high rates of mortality and severe disability in TENSION also underscore that successful reperfusion alone is insufficient to fully modify the clinical trajectory of large-core infarction. Post-reperfusion injury, malignant edema, hemorrhagic transformation, delayed neurological deterioration, and systemic complications may continue to influence outcomes even after technically successful thrombectomy. In particular, extensive baseline infarction may render patients more vulnerable to secondary injury cascades, including reperfusion injury, edema progression, and hemodynamic instability. However, most large-core EVT trials, including TENSION, primarily evaluated the efficacy of reperfusion and did not standardize specific post-EVT neurocritical care strategies. Although decompressive craniectomy was permitted, other anti-edema approaches, such as osmotic therapy or therapeutic hypothermia, were not evaluated as protocol-driven interventions. Similarly, optimal blood pressure targets after EVT remain unresolved, particularly in patients with extensive infarction, in whom aggressive lowering may reduce reperfusion injury but may also compromise vulnerable collateral-dependent tissue (14-17). Although the exact thresholds and study populations differed, three recent randomized controlled trials converge on the finding that intensive blood pressure lowering following successful thrombectomy does not confer benefit and may cause harm relative to conventional targets, with two of the three trials stopped early because of safety or futility concerns (14-16). These findings are further supported by observational data suggesting that blood pressure variability, rather than the absolute target level, may be an independent contributor to outcome (17). Future studies should therefore move beyond the binary question of reperfusion and focus on individualized post-EVT care strategies, including blood pressure management, edema control, hemorrhagic transformation prevention, systemic complication reduction, and mitigation of secondary neurological injury.

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