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The publication of the DAWN (DWI or CTP Assessment with Clinical Mismatch in the Triage of Wake-up and Late Presenting Strokes Undergoing Neurointervention with Trevo) trial is yet another milestone in the endovascular management of acute stroke.1 DAWN extends the application of mechanical thrombolysis (MT) beyond previously established time frames and builds upon the positive results of earlier, randomized controlled trials that demonstrated the clear superiority of MT in the treatment of emergency large vessel occlusion (ELVO).2–6
Specifically, the study evaluated outcomes at 90 days in ELVO patients with neurological deficits that were disproportionately severe in comparison to their infarct volumes as assessed by diffusion-weighted MRI or perfusion CT. Patients were last known well 6 to 24 hours before presentation. The efficacy of MT plus standard medical care was compared with standard medical care alone. The trial was halted at 31 months when a pre-specified interim analysis determined that patients in the thrombectomy group had a higher likelihood of functional independence (49% vs 13% at 90 days) and higher scores on the utility-weighted modified Rankin scale (5.5 vs 3.4 at 90 days). These results demonstrated a clear benefit for MT in ELVO patients presenting beyond previously established time windows, including the large group of patients with ‘wake up’ strokes.
Enrollment in the trial was strictly adjudicated and patients were randomized in a 1:1 ratio to the two treatment groups. Only patients with ICA terminus or M1 occlusion or both were eligible for enrollment. The initial clinical assessment was conducted using the National Institutes of Health Stroke Scale (NIHSS) and infarct volumes were calculated using the RAPID automated patient selection software. Twenty-six centers that averaged at least 40 MT procedures annually participated in the study. Two primary endpoints were established: the first was the mean score for disability on the utility-weighted modified Rankin scale, and the second was the rate of the functional independence (mRS of 0, 1, or 2) at 90 days. Trial enrollment was halted when a pre-specified interim analysis identified a predictive probability of the superiority of MT of at least 95% in achieving the first primary endpoint.
The MT techniques employed in the trial were also well-defined. In 102 of 105 cases, MT was performed with use of the Trevo retrievable self-expanding stent (Stryker Neurovascular). Three patients in the treatment group underwent carotid angioplasty prior to MT. Carotid stenting was not allowed. Moderate sedation and/or monitored anesthesia care, rather than general anesthesia, was utilized in 90% of cases. Using these methods, recanalization, defined as a Thrombolysis in Cerebral Infarction score of 2b or 3, was achieved in 84% of patients undergoing MT. This compares favorably to the HERMES meta-analysis data, in which recanalization was achieved in 71%.7 Importantly, the rates of adverse events such as stroke-related death within 90 days, death from any cause within 90 days and symptomatic intracerebral hemorrhage at 24 hours did not differ significantly between the treatment and control groups. Patients in the control group were also nearly twice as likely to suffer neurological deterioration within 24 hours in comparison to the MT group (26% vs 14%; P=0.04).
These outstanding technical results translated into a dramatic improvement in patient outcomes. DAWN revealed that for every two patients treated with MT, one additional patient had less disability at 90 days. Similarly, for every 2.8 patients undergoing MT, one more patient achieved functional independence. Regarding functional independence, this result is virtually identical to the meta-analysis of the pooled data for the previously published randomized trials in which most patients were treated within 6 hours of their ictus (49% DAWN vs. 46% HERMES).7
DAWN is yet another in the series of trials halted because of the clear superiority of MT over non-endovascular comparators. The positive results of the MR CLEAN study prompted interim analysis and closure of the ESCAPE, EXTEND-IA, SWIFT PRIME, and REVASCAT trials. Recently, the DEFUSE three trial (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke 3) also closed enrollment after MT was shown to be superior to standard medical treatment alone in patients last known well between 6 and 16 hours from their strokes.8 DEFUSE 3, which has yet to be published, differed from DAWN in that patients with larger core infarcts were enrolled as long as they demonstrated evidence of salvageable tissue on perfusion/diffusion imaging. These trials have not only conclusively extended the time window for treatment of ELVO they have demonstrated the critical importance of modern imaging techniques in identifying those patients that would benefit most from treatment. Trials that employ modern devices and appropriate imaging selection have made MT the standard of care in the treatment of ELVO.9 10 As a result, the number of patients being treated utilizing these techniques has increased at a rapid pace.11
Although DAWN verified that stroke patients could be treated safely and with proven benefit up to 24 hours after suffering a stroke, those patients treated earlier still had better outcomes. Further refinements in our stroke systems of care are essential in reducing the time to intervention.12 Several articles in this month’s issue address this optimal time frame and which patients are ideal candidates for intervention.13–15 In addition, Goyal et al continue their analysis of ELVO patients not meeting top tier evidence for treatment, reporting that this cohort had good clinical outcomes and an acceptably low rate of complications after MT.13
After DAWN and the other positive trials, we must continue our investigations into what other groups of patients could benefit from endovascular treatment.16 To this end, Mourand et al evaluated their institutional experience with MT in patients with large core infarcts (ASPECTS </=5).17 Compared with patients treated medically, the MT group had significantly reduced disability and lower rates of hemicraniectomy and death at 90 days. In their accompanying commentary, Chen and Mocco argue for a randomized trial assessing the safety and efficacy of MT in patients with low ASPECTS scores.18
Current and future trials that adhere to the rigorous methodology employed in DAWN and the other positive trials have the potential to reduce dramatically the rate of stroke-related disability. The socio-economic impact of this accomplishment would be unprecedented. As neurointerventionalists wake to the DAWN of this new era in stroke care, one thing is certain: these are wonderful times for our field and, more importantly, for our patients.
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Footnotes
Contributors All authors contributed to the conception, drafting, and final approval of manuscript.
Competing interests None declared.
Provenance and peer review Commissioned; internally peer reviewed.