The MAGNA meta-analysis of individual patient data (IPD) has provided “strong, generalisable evidence” on the clinically meaningful benefits of endovascular therapy (EVT) in ischaemic stroke patients with a large-core infarct volume. Late-breaking findings from MAGNA were presented by Amrou Sarraj (Case Western Reserve University, Cleveland, USA) on the final day of the European Stroke Organisation Conference (ESOC; 24–26 May, Munich, Germany).
“The MAGNA IPD meta-analysis provides strong evidence for clinically meaningful benefit in reducing disability for patients with extensive ischaemic injury on non-contrast CT [computed tomography], CTP [CT perfusion] or MRI [magnetic resonance imaging],” he stated. “The results from the previously published large-core trials, and from this pooled dataset, provide unequivocal evidence on the efficacy and safety of EVT in patients with large-core infarcts. The benefit persists across the spectrum of age, clinical severity and time with clear benefit up to an estimated ischaemic core volume of 150ml.”
Discussing the ongoing expansion of EVT in acute ischaemic stroke care, Sarraj initially noted that patients with large-core infarcts have been excluded from many prior trials evaluating this intervention, but that three more recent randomised controlled trials (RCTs)—RESCUE-Japan LIMIT, ANGEL-ASPECT and SELECT2—have indicated that EVT can safely provide clinical benefits in these patients.
As such, data from these three RCTs were collated by the MAGNA investigators in an effort to explore the evidence favouring EVT over standard medical care in large-core infarct patients presenting up to 24 hours from time last known well across key clinical and imaging subgroups. The meta-analysis’ primary efficacy endpoint was the distribution of scores on the modified Rankin scale (mRS) at 90-day follow-up, while secondary endpoints included functional independence (mRS 0–2), independent ambulation (mRS 0–3), symptomatic intracranial haemorrhage (sICH) and mortality.
Patients were considered eligible if their anterior-circulation large vessel occlusion had an ischaemic core with an Alberta stroke programme early CT score (ASPECTS) ≤5 on non-contrast CT or MRI, or if the core volume was ≥50ml. In total, 1,009 patients (41% female) were included, of whom 506 received EVT and 503 received standard care.
MAGNA analyses found that EVT improved functional outcomes—as per the primary efficacy endpoint—as well as functional independence and independent ambulation compared to medical management, but was also associated with more frequent early neurological worsening. Sarraj described this as a “continuation” of a similar trend seen in the SELECT2 trial. In addition, no significant difference in mortality was identified between EVT and standard care, and sICH rates were similar between the two groups as well.
According to Sarraj, key subgroup analyses also “consistently favoured” EVT, and the benefits of EVT were found to have reached statistical significance over medical management across ASPECTS 3, 4 and 5. Additionally, EVT was statistically significantly superior in ischaemic cores with volumes ranging from <70ml up to 149ml, but not in those ≥150ml.
After re-emphasising the persistent benefit of EVT across many of the endpoints assessed and a “wide spectrum” of large-core infarct patients in MAGNA, Sarraj concluded his talk by stating that “clinical judgement is required to weigh [up] the influence of individual patient factors” on these benefits, including co-morbidity, frailty, and tolerance of disability. He further noted that the “consistency in the results” and “magnitude of the treatment effect” emphasise the generalisability of these findings “across the large-core population”.
“There is no going back,” Sarraj summarised. “We showed efficacy, we showed safety, and we really look forward to the guidelines changing sooner rather than later.”
In a discussion following his presentation, Sarraj alluded to the fact that the results of the TESLA study—presented earlier on in the same plenary session at ESOC 2023—also favour EVT versus standard care, despite the trial failing to meet its prespecified primary endpoint, owing to the “positive efficacy signals” and “good safety outcomes” reported.
The MAGNA investigators’ attention will now turn toward the final results from TESLA, as well as two more as-yet unpublished large-core infarct trials—LASTE and TENSION—as they plan to update their meta-analysis once these data are available.
“This will increase the accuracy of the estimation of the treatment effect, and will give even more power to look further into the details related to subgroups and selected imaging modalities,” Sarraj added.
Discussions following Sarraj’s talk also saw Philip Bath (University of Nottingham, Nottingham, UK) comment that there is a tendency to “merge” mRS scores of 5 and 6 together in research projects such as this. But, as the two scores can be “very diverse” in reality, Bath suggested that the investigators should not do this in their final meta-analysis; Sarraj responded favourably, noting that there is “value and additional information” that can be gleaned from reporting mRS 5 and 6 separately, in addition to evaluating them in combination.
A systematic review and meta-analysis assessing the three RCTs mentioned here as well as 10 cohort studies has since been published in Neurology, ultimately delivering a similar conclusion—EVT can improve functional outcomes without increased sICH risks versus medical management in large-core ischaemic strokes, and insights from other, ongoing trials will provide further insights.