Elena Zapata-Arriaza, MD
Leslie-Mazwi TM, Hamilton S, Mlynash M, Patel AB, Schwamm LH, Lansberg MG, et al. DEFUSE 3 Non-DAWN Patients: A Closer Look at Late Window Thrombectomy Selection. Stroke. 2019;50:618–625.
The recently released DEFUSE 3 and DAWN trials have demonstrated the effectiveness and safety of thrombectomy in extended time window, beyond 6 hours. However, given the restraint in inclusion criteria of the DAWN trial, the assessment of endovascular therapy in DEFFUSE 3 patients who would have been excluded for DAWN will guide us about thrombectomy effect in other subgroups.
To resolve this mentioned purpose, the authors applied eligibility criteria of the DAWN trial to DEFUSE 3 patient data to identify DEFUSE 3 patients not meeting DAWN criteria (DEFUSE 3 non-DAWN). Reasons for DAWN exclusion in DEFUSE 3 were infarct core too large, National Institutes of Health Stroke Scale (NIHSS) score 6 to 9, and modified Rankin Scale score of 2. Only 13 DEFUSE 3 patients had a prestroke mRS of 2, which was inadequate to address whether these patients had a favorable response to thrombectomy; therefore, these patients were categorized by their NIHSS score. Analysis was performed for core to large (CTL) versus core-not-too-large (CNTL) patients and for NIHSS 6 to 9 versus NIHSS ≥10 patients. Subgroups were compared with the DEFUSE 3 non-DAWN and entire DEFUSE 3 cohorts.
After applying the eligibility criteria of the DAWN trial to the DEFUSE 3 data, 71 enrolled DEFUSE 3 non-DAWN–eligible patients were identified, with the following reasons for ineligibility: 31 patients with NIHSS too low (presentation scores of 6–9), 33 patients with infarct CTL and 13 patients with baseline mRS of 2 at presentation.
Regarding subgroups analysis, in CTL patients no differences in functional outcome were seen between the 2 groups (mRS of 0–2 in 24% of the CTL versus 32% of the CNTL group), despite significant differences in infarct growth between enrollment and 24-hour scans (larger in CTL subgroup), enrollment age (older rate in CTL group) (Figure 1). For this subgroup of patients, after adjustment for prognostic factors of age and NIHSS, the odds ratio for functional outcome was 20.9. In addition, rates of death and symptomatic intracranial hemorrhage were equivalent between the 2 groups. Time from onset to reperfusion, target reperfusion were also similar.
In NIHSS 6 to 9 patients subgroup assessment, no differences were identified between subgroups for process timing and reperfusion rates. However, functional independence was more likely in the low NIHSS group [74% in the NIHSS 6 to 9 vs 3 22% of the NIHSS ≥10 group (P<0.001)]. Six percent of the NIHSS 6 to 9 group died, compared with 23% of the NIHSS ≥10 group (P=0.024). Figure 2 shows the mRS distributions for the DEFUSE 3 non-DAWN patients treated with endovascular versus best medical management for the NIHSS 6 to 9 and the NIHSS ≥10 groups.
Patients with CTL (within the established limits by DEFFUSE 3 trial) benefit from endovascular treatment, despite differences in age groups, final infarct size, infarct growth and other factors. It is remarkable that not all those strokes with a large final size will obtain clinical benefit, since this data is unknown. The core it is not the only factor that influences clinical outcome, since the affected hemisphere, or the eloquence of the damaged area contribute final results. It is outstanding the fact of maintaining similar rates of cerebral haemorrhage and deaths despite the difference in the final infarct sizes. Such results may lead us to think, as the authors highlight in the paper, that these patients do not receive intravenous thrombolysis, thus reducing the hemorrhages associated with such treatment. Therefore, it is possible that the hemorrhagic risk of the endovascular procedure alone is less than that which occurs when fibrinolysis is associated, giving important margins of safety in these patients. In any case, from this article, we would simplify the selection of patients candidates for thrombectomy, allowing all those patients with strokes between 6-24 h, with a maximum core of 70 ml regardless of age or the NIHSS score (as long as it is greater than 6). Regarding the subgroup of low NIHSS, it would be logical these strokes are related to a better functional prognosis since they are milder strokes with less risk of presenting neurological and systemic complications.
The thrombectomy has already shown its effectiveness and safety against medical treatment alone, and this study, therefore, seeks to increase the number of candidates to experience an evident clinical improvement without increasing the damage derived from the treatment.