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Page 2 of 9 Linger et al. Vessel Plus 2020;4:36 I http://dx.doi.org/10.20517/2574-1209.2020.51

Occlusion with Emphasis on Minimizing CT to Recanalization Times (ESCAPE); Solitaire With the
Intention For Thrombectomy PRIMary Endovascular Treatment (SWIFT PRIME); and Randomized
Trial of Revascularization with Solitaire FR Device vs. Best Medical Therapy in the Treatment of Acute
Stroke Due to Anterior Circulation Large Vessel Occlusion Presenting within Eight Hours of Symptom
Onset (REVASCAT)] demonstrating benefit in patients presenting with large vessel occlusion (LVO) of
[1-5]
the anterior circulation within 6 h of symptom onset . LVO in the anterior circulation is defined as an
occlusion of the intracranial internal carotid artery and/or the first segment of the middle cerebral artery
(M1). Patients with intracranial occlusion and tandem extracranial carotid artery occlusion were also
included in the trials and clearly benefitted. In an individual patient data meta-analysis of these trials, the
rate of functional independence [defined as a modified Rankin scale (mRS) score of 0-2] was significantly
higher in the thrombectomy cohort (46%) compared to medical therapy (27%), equaling a number-
needed-to-treat (NNT) of 5 . There was a similar rate of serious adverse events, in particular symptomatic
[6]
[6]
intracranial hemorrhage, between thrombectomy and medical therapy groups . These results were in
[7-9]
contrast to 3 previous trials published in 2013 that failed to show clinical benefit of thrombectomy . The
difference in outcomes is likely explained by improvements in patient selection (detecting LVO with non-
invasive imaging prior to angiography), faster door-to-arterial access times and better devices to achieve
[10]
faster and more complete reperfusion . The THRACE (Mechanical Thrombectomy After Intravenous
Alteplase vs. Alteplase Alone After Stroke), PISTE (Pragmatic Ischaemic Stroke Thrombectomy Evaluation)
and RESILIENT (Randomisation of endovascular treatment with stent-retriever and/or thromboaspiration
vs. best medical therapy with acute ischemic stroke due to large vessel occlusion) trials were also
subsequently reported with consistent results in favor of thrombectomy [11-13] .

Data from the MR CLEAN trial indicate that the benefit of thrombectomy, when patient selection is
simply based on evidence of LVO using non-invasive imaging, is strongly time-dependent and ceases
[14]
to be statistically significant ~6 h after onset . The HERMES (Highly Effective Reperfusion Evaluated
in Multiple Endovascular Stroke Trials) pooled data found statistically significant benefit out to 7.3 h
but included patients selected on the basis of good collateral flow or favorable CT perfusion which has
subsequently been shown to extend the time window for treatment .
[15]

The DAWN trial (DWI or CTP Assessment with Clinical Mismatch in the Triage of Wake-Up and Late
Presenting Strokes Undergoing Neurointervention with Trevo) in patients 6-24 h after the time they
were last known to be well used clinical-core mismatch imaging selection. This involved CT perfusion or
diffusion MRI to identify a relatively small volume of irreversibly injured brain (ischemic core) compared
[16]
to the severity of clinical deficit and also factored in patient age . CT perfusion has been shown to achieve
[17]
similar perfusion mismatch classification compared to MRI . Volumetric agreement studies have shown
that overestimation of ischemic core using a relative cerebral blood flow threshold < 30% of normal brain
[18]
is uncommon and tends to involve white matter in patients with ultra-rapid reperfusion [19-21] . The DEFUSE
3 trial (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke) in patients 6-16 h after
the time they were last known to be well used CT perfusion or MRI perfusion-diffusion mismatch and
required < 70 mL irreversibly injured ischemic core combined with the critically hypoperfused region
[22]
being both > 15 mL and > 1.8 times the volume of the ischemic core . In the DAWN and DEFUSE 3 trials,
the NNT for functional independence (defined as mRS score 0-2) was 2.8 and 3.6, respectively [16,22] . There
was no significant difference in the rate of symptomatic intracerebral hemorrhage between thrombectomy
and medical therapy groups in these trials. The DEFUSE 3 inclusion criteria classified ~60% more patients
as eligible for thrombectomy than the DAWN criteria and these additional patients benefitted at least as
[22]
much from the thrombectomy procedure . Perfusion imaging selection is therefore recommended in
international guidelines for selection of patients for thrombectomy 6-24 h after the time they were last
known to be well [Figure 1] [23,24] . Relatively few patients present with LVO beyond 24 h, and a trial is
unlikely to be feasible. However, anecdotal reports have suggested potential benefit in patients > 24 h after
onset if imaging is favorable .
[25]