The recent influx of positive endovascular trials in acute ischemic stroke (AIS) has forged a change in paradigm that is still evolving. Eight pivotal trials, including IMS III and MR CLEAN, have shaped our current guidelines (published in the October edition of Stroke) and have provided the stroke community with new data for further pooled analyses.

Hereof, based on the data of the most severe (NIHSS ≥20) AIS participants from the IMS III and MR CLEAN trials, the authors aimed to determine whether individuals who underwent endovascular treatment in addition to intravenous (IV) t-PA within 6 hours from symptom onset had improved 90-day outcomes compared to those who received IV t-PA alone. All subjects with severe strokes prior to IV t-PA treatment (IMS III) or randomization (MR CLEAN) who received t-PA within 3 hours of stroke onset were included. The methodological differences between the two trials were many and described in detail in the paper, however the lack of required vascular imaging prior to enrollment and the limited use of stent retrievers (~12% vs. 82%) in IMS III versus MR CLEAN constituted some of the most salient discrepancies. The primary outcome was the modified Rankin Scale (mRS) at 90 days. Secondary outcomes were Barthel Index (BI) and the EQ-5D-3L health-related quality-of-life (EQ-5D-3L). The pre-specified covariates for the adjusted analysis included NIHSS, age, previous stroke, diabetes and atrial fibrillation. A comparison of the proportion of symptomatic intracranial hemorrhage (sICH) and the TICI 2b3 scores between the two groups were also reported.

Among the 342 patients included in the pooled analysis, the endovascular group had overall superior functional outcomes as measured per the 90-day mRS (ordinal regression; adjusted OR 1.78) [Figure], with a 2-fold increase in functional independence (mRS≤2, aOR 1.97), as well as significant improvements in BI (aOR1.80) and EQ-5D-3L (adjusted regression coefficient of 0.10) scores, in comparison to the IV t-PA group. When looking into safety, the proportion of sICH was not significantly different between groups. Finally, TICI 2b3 reperfusion score was reached in 45% for the pooled cohort although no comment regarding differences between treatment groups was made.
                      Figure: Distribution of 90-day outcomes for the pooled cohort.

While limited by methodologic differences between the trials, this pooled analysis of IMS III and MR CLEAN demonstrates that endovascular therapy following IV t-PA within 3 hours from symptom onset improves functional outcome at 90 days in AIS patients presenting with severe neurologic deficits. The findings reinforce the overwhelming therapeutic effect on endovascular therapy in AIS patients observed in the other mechanical thrombectomy trials published following MR CLEAN. Pooled analysis including all recently published stent retriever trials are surely underway and much awaited!