The most inclusive criteria from both trials should be adopted, experts conclude.
Patients who were excluded from thrombectomy in the DAWN trial due to the size of their infarct core or NIHSS score, but who would have been eligible based on DEFUSE 3 criteria, likely still benefit from the procedure, a new study suggests.
The findings were recently presented at the 2019 International Stroke Conference in Honolulu, HI, and published online, ahead of print, in Stroke.
“DEFUSE 3 was a trial that had less restrictive criteria than DAWN,” lead author Thabele M. Leslie-Mazwi, MD (Massachusetts General Hospital, Boston), told Neurovascular Exchange. “As we think about expanding our [endovascular thrombectomy] treatment, one of the big ways to do that is to treat people that are currently considered more marginal. . . . If you take all of the DEFUSE 3 patients who were not DAWN-eligible and you examine them as a group, there was a strong signal for benefit of endovascular therapy.
He and his colleagues wanted to find out whether this subpopulation was homogenous or heterogenous, Leslie-Mazwi said, “and does the difference in that signal between the subtypes in that non-DAWN population give us information on where we should focus next?”
Leslie-Mazwi et al applied the eligibility criteria for thrombectomy from the DAWN trial to data from DEFUSE 3, identifying 71 patients who were eligible for thrombectomy using DEFUSE 3 but not DAWN criteria. Among these patients, reasons for exclusion in DAWN were NIHSS score of 6-9 (n = 31), infarct core too large (n = 33), and premorbid mRS score of 2 (n = 13). Some patients met multiple exclusion criteria.
Among patients who were excluded for large core, the median 24-hour infarct volume was 119 mL (IQR 74.6-180 mL), compared with 31.5 mL (IQR 17.6-64.3 mL) in those with acceptable infarct core size (P < 0.001). Complications and functional outcomes were similar between the groups. Thrombectomy in patients with large infarct core, compared with the remaining patients who were eligible for DEFUSE 3 but not DAWN, provided benefits in functional outcome (OR 20.9; 95% CI, 1.3-337.8).
An mRS 0-2 was achieved in 74% of patients with an NIHSS score of 6-9, compared with 22% of those with an NIHSS score ≥ 10 (P < 0.001). Mortality was 6% in the NIHSS 6-9 group versus 23% in the NIHSS ≥ 10 group (P = 0.024). Among patients with an NIHSS score of 6-9, compared with the remaining DEFUSE 3 patients not eligible for DAWN, the use of thrombectomy was associated with a trend toward a better chance of functional outcome (OR 1.86; 95% CI 0.36-9.53).
Expand the Criteria for Endovascular Thrombectomy
In a joint comment on the study for NVX, Ashutosh Jadhav, MD and Shashvat Desai, MD (both from University of Pittsburgh Medical Center, PA), point out that while DAWN was the more restrictive study, it was still was more inclusive than DEFUSE 3 in some respects. “While DEFUSE-3 . . . included patients with a core volume up to 70 mL and NIHSS 6 or more, the DAWN trial studied patients up to 24 hours and did not exclude nonagenarians,” they pointed out.
“The main clinical implication is that even patients with large cores (up to 70 mL) achieved benefit with thrombectomy without higher rates of symptomatic intracerebral hemorrhage,” they continue. “Given that more than a third of each trial’s eligible cohort do not meet criteria for the other trial, it would be impractical to stick to just one trial criteria. In our opinion, the most permissive combination of criteria should be used universally: age ≥ 18, NIHSS ≥ 6, stroke onset within 24 hours, ischemic core up to 70 mL, and baseline mRS 0-2. Choice of thrombectomy device should rest with the treating interventionalist, similar to the DEFUSE 3 study.”
Leslie-Mazwi takes a slightly more conservative approach, for now suggesting an expansion of the criteria only to larger infarcts. “For the group who had core infarcts that were too large for DAWN (50-70 mL) the benefit of the endovascular intervention was extremely strong,” even if they had infarct volumes over 100 mL in their final measurements or infarct growth, and despite the fact that 40% were older than 80 years, he said to NVX.
“If we are looking to grow the population of patients that we can treat in the late window, the low-hanging fruit is likely to be people with larger cores because that signal of benefit has not reached a point where it tips into insignificance,” he explained, recommending that centers immediately begin expanding indications for endovascular therapy in patients with infarcts up to 70 mL.
The threshold at which the infarct core becomes so large that the risks of endovascular therapy likely outweigh the benefits is yet to be determined, Leslie-Mazwi acknowledged. In addition, there remains the question of how much penumbra size impacts the likelihood that patients with large cores with benefit from endovascular therapy. Only patients with large penumbras were eligible for DEFUSE 3.
Leslie-Mazwi and the commenting experts agree that the small sample size may explain why there was only a trend toward benefit with endovascular thrombectomy in the NIHSS 6-9 group. Additional research is needed to confirm the best way to treat these patients.
Leslie-Mazwi TM, Hamilton S, Mlynash M et al. . Stroke. 2019;Epub ahead of print.
Leslie-Mazwi, Jadhav, and Desai report no relevant conflicts of interest.