Abstract 73: Results of DEFUSE 2: Clinical Endpoints
Authors: Lansberg Maarten G , Kemp Stephanie , Straka Matus , Mlynash Michael , Wechsler Lawrence R , Jovin Tudor G , Wilder Michael J , Lutsep Helmi L , Czartoski Todd , Bernstein Richard A , Chang Cherylee W , Warach Steven , Fazekas Franz , Thai Demi , Inoue Manabu , Tipirneni Aaryani , Hamilton Scott A , Zaharchuk Greg , Marks Michael P , Bammer Roland , Albers Gregory W ,   The DEFUSE 2 Investigators
Published: March 2022

Background:
The aim of DEFUSE 2 was to determine if there is a differential response to reperfusion following endovascular therapy according to predefined baseline MRI profiles.

Methods:
This prospective cohort study was conducted at 9 stroke centers. Consecutive patients, scheduled to undergo acute endovascular therapy within 12 hours of stroke onset, were enrolled if they had an NIHSSS>5 and could undergo an MRI with perfusion (PWI) and diffusion-weighted imaging (DWI) immediately before the intervention. A fully automated image analysis program (RAPID) was used to determine lesion volumes. Patients were classified as Target Mismatch (TMM) if they met these criteria: a ratio of PWI(Tmax>6s) over DWI volume >1.8, DWI <70ml, and a PWI(Tmax>10s) volume <100ml. An early follow-up MRI was obtained <12 hours after endovascular therapy. Early reperfusion was defined as a >50% reduction in Tmax>6s volume between baseline and early follow-up. Favorable clinical response was defined as a ≥8 point improvement on the NIHSSS or an NIHSSS of 0-1 at 30 days.

Results:
This abstract represents a preliminary analysis of 86 of 101 patients who were treated with endovascular therapy (final results will be presented). The baseline characteristics of patients with TMM (n=70) were: mean age 67, median NIHSS 15, treated with iv tPA 43%, mean time from symptom onset to endovascular treatment 6.7 hrs, mean DWI volume 18 ml, and Tmax>6s volume 82 ml. Early reperfusion was achieved in 64% of the TMM population and favorable clinical response was more common in TMM patients with early reperfusion than in TMM patients who did not reperfuse (69% vs 24%; p<0.001). The baseline characteristics of patients without TMM (n=16) were: mean age 59, median NIHSS 19, treated with iv tPA 81%, mean time from symptom onset to endovascular treatment 5.4 hrs, mean DWI volume 76 ml, and Tmax>6s volume 115 ml. Early reperfusion was achieved in 53% of the patients without TMM but was not associated with favorable clinical response in this population (44% had favorable clinical response with reperfusion vs 86% without reperfusion; p=0.15). The odds ratio for favorable clinical response associated with reperfusion was higher in TMM patients (7.0; 95% CI 2.3-21) than in those without TMM (0.1; 95% CI 0.1-1.6) (p<0.01 for difference between odds ratios). These odds ratios remained similar after adjustment for differences in baseline characteristics (OR 7.8 vs. 0.2; p<0.01 for difference between odds ratios).

Conclusion:
Early reperfusion following endovascular therapy is associated with substantial clinical benefits in patients with the Target Mismatch profile on baseline MRI. There is no association between reperfusion and favorable clinical outcomes in patients without Target Mismatch. These findings support the use of PWI/DWI selection criteria to identify a patient subgroup that is most likely to benefit from endovascular reperfusion therapy.