DAWN: extended-window thrombectomy

Throughout the 2000s, attempts to extend mechanical thrombectomy beyond a narrow time window had failed in trial after trial. Each failure reinforced the belief that neurons lost to ischemia over hours could not be salvaged by late intervention. The underlying assumption was that time-from-onset and tissue viability were essentially synonymous. What that assumption missed was that collateral circulation varies enormously between patients, and some individuals retain viable penumbra many hours after a large-vessel occlusion. DAWN was designed to test whether selecting patients by clinical-imaging mismatch rather than by clock time could identify that salvageable group.

Raul Nogueira led the DAWN trial with Tudor Jovin as a key co-investigator, enrolling patients at multiple sites across the United States, Europe, and Australia. The trial enrolled 206 patients presenting with anterior large-vessel occlusion between 6 and 24 hours after last-known-well, selecting candidates whose infarct core on diffusion-weighted imaging or CT perfusion was disproportionately small relative to their neurological deficit. That mismatch implied penumbra that remained viable despite the elapsed time. The control arm received best medical management; the intervention arm received thrombectomy with the Trevo stent retriever.

The data safety monitoring board stopped the trial early after a prespecified interim analysis showed 49% of thrombectomy patients had achieved functional independence at 90 days, compared with 13% in the medical management group. That 36-percentage-point absolute difference was larger than the benefit seen in the 0-to-6-hour thrombectomy trials that had established the procedure just three years earlier. The early stopping meant the final enrollment was smaller than planned, but the magnitude of benefit left little statistical uncertainty.

DAWN's companion trial, DEFUSE 3, published at nearly the same time, confirmed the benefit in a 6-to-16-hour window using automated perfusion software to identify the mismatch, and was also stopped early for efficacy. Together, the two trials shifted stroke intervention from a time-based to an imaging-based selection model. The American Heart Association updated its stroke guidelines in early 2018 to incorporate both trials, and thrombectomy centers rapidly added late-window protocols. Patients found hours after symptom onset, or those who woke with deficits without a known onset time, became eligible for a procedure that had previously been unavailable to them.