Determining optimal patient selection criteria for endovascular thrombectomy 6 hours after symptom onset

Analysis of pooled data from six randomized clinical trials (RCTs) showed that patients who met the imaging profiles of the DAWN and DEFUSE 3 trials and underwent endovascular thrombectomy (EVT) in the late window (6-24 hours) had significant improvements in clinical outcomes at 90 days.

The findings by Dr. Greg Albers and colleagues were published in JAMA Neurology.

Key takeaways:

• Patients who met the DAWN (clinical mismatch) or DEFUSE 3 (target mismatch) imaging profiles and were treated with EVT in the late window (6-24 hours) showed significant improvements in clinical outcomes. This treatment effect was significantly larger than observed in patients who did not have perfusion imaging and therefore had an undetermined imaging profile.
  
• More patients fit the target mismatch profile than the clinical mismatch profile and the results of this study show that target mismatch can be used up to 24 hours to select patients.

Significance of DAWN and DEFUSE 3 trials in acute ischemic stroke management

In 2018, two landmark RCTs, DAWN and DEFUSE 3, proved that selected patients diagnosed with acute ischemic stroke can be treated with EVT for up to 24 hours from the onset of symptoms. In both these trials, the Rapid imaging platform was used to process the CT perfusion (CTP) or MRI scan data.

These trials led the American Heart Association and American Stroke Association to extend the treatment window for EVT in eligible patients from 6 to 24 hours following the onset of symptoms, enabling more patients to benefit from life-saving treatment.

The DAWN and DEFUSE 3 trials demonstrated the benefits of EVT in patients with slow infarct growth rate and good collaterals in the extended treatment window.

Selecting patients eligible for EVT in the extended treatment window

The imaging profiles for patient selection were different for DAWN and DEFUSE 3.

The DAWN trial used CTP or MRI scan data processed by Rapid software to evaluate clinical mismatch (size of early infarction vs presenting clinical deficits) and select patients eligible for EVT.

The DEFUSE 3 trial used CTP or MRI scan data processed by Rapid software to evaluate target mismatch (size of early infarction vs size of perfusion lesion) and select patients eligible for EVT.

The target mismatch criteria is more generous, and more patients can be treated using this criteria.

The AURORA study (Analysis of Pooled Data from Randomized Studies of Thrombectomy More Than 6 Hours After Last Known Well)      

The AURORA database was created by pooling data from six RCTs that enrolled patients with anterior circulation ischemic stroke 6 hours after symptom onset and treated them with second-generation neurothrombectomy devices. That is, data from DAWN, DEFUSE 3, REVASCAT, ESCAPE, RESILIENT, and POSITIVE trials.

Data of patients whose CTP or MRI scan, baseline NIHSS, and 90-day mRS profiles were available were included. All CTP and MRI scans of patients selected for inclusion in the AURORA database were processed using Rapid software.

Based on the baseline imaging profile and NIHSS, patients were categorized into three groups:

1) Patients who met the clinical mismatch criteria (similar to DAWN)

2) Patients who met the target mismatch criteria (similar to DEFUSE 3)

3) Patients whose imaging profile could not be determined because of inadequate scan.

To determine the optimal imaging profile to select patients eligible for EVT in the extended treatment window (6-24 hours), the clinical outcomes in patients belonging to the three groups were compared.

Data from 504 patients were analyzed as part of the study, out of which 266 patients were treated with EVT, and 239 were part of the control group.

Patients selected for EVT using DAWN or DEFUSE 3 imaging profiles showed significant clinical improvements

Association between imaging profile and clinical outcomes

Data analysis showed that patients in the clinical mismatch and target mismatch groups who underwent EVT had significant treatment effects. They had lower overall disability and higher likelihood of functional independence at 90 days in comparison with their respective control groups.

The clinical outcomes were not significant for patients with an undetermined imaging profile.

Association between imaging profile and clinical outcomes across the 24-hour window

Patients in the clinical mismatch and target mismatch groups were further classified based on the time at which they received treatment following symptom onset:

1) 6.0 — 9.5 hours

2) 9.6 — 12.7 hours

3) 12.8 — 24 hours.

Significant treatment benefits were observed in patients belonging to all three-time terciles in both clinical mismatch and target mismatch groups, with the highest odds ratio in patients belonging to the third time tercile (12.8-24 hours) of the target mismatch group.

The AURORA database analysis further confirms the benefits of using either of the mismatch profiles to select patients eligible for EVT in the extended treatment window.