Response to endovascular reperfusion is not time-dependent in patients with salvageable tissue

Lansberg, Maarten G.; Cereda, Carlo; Mlynash, Michael; Mishra, Nishant K.; Inoue, Matsuhisa; Kemp, Stephanie; Christensen, Søren; Straka, Matús; Zaharchuk, Greg; Marks, Michael P.; Bammer, Roland; Albers, Gregory W.

doi:10.1212/wnl.0000000000001853

Cited by 87 publications

(55 citation statements)

References 27 publications

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“…This suggestion is supported by our finding that the positive association between reperfusion and rate of functional independence was similar among target mismatch patients who were treated early (<6 hours) and those who were treated late (>6 hours); a result that is consistent with our findings in DEFUSE 2, which demonstrated that the effect of reperfusion was similar among early and late treated patients with an MRI target mismatch pattern. [10] Our finding that rates of symptomatic intracranial hemorrhage (sICH) were almost identical among early and late treated patients (5.2 vs 5.3%) points to the safety of endovascular treatment of patients with target mismatch in the delayed time-window (>6 hours).…”

Section: Discussionmentioning

confidence: 94%

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Computed tomographic perfusion to Predict Response to Recanalization in ischemic stroke

Lansberg

Christensen

Kemp

et al. 2017

Annals of Neurology

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116

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Objective To assess the utility of CT perfusion for selection of patients for endovascular therapy up to 18 hours after symptom onset. Methods We conducted a multicenter cohort study of consecutive acute stroke patients scheduled to undergo endovascular therapy within 90 min after a baseline CTP. Patients were classified as ‘target mismatch’ if they had a small ischemic core and a large penumbra on their baseline CT perfusion. Reperfusion was defined as >50% reduction in critical hypoperfusion between the baseline CT perfusion and the 36-hour follow-up MRI. Results Of the 201 patients enrolled, 190 patients with an adequate baseline CT perfusion study who underwent angiography were included; mean age 66 years, median NIHSS 16, median time from symptom onset to endovascular therapy 5.2 hours. Rate of reperfusion was 89%. In patients with target mismatch (n=131), reperfusion was associated with higher odds of favorable clinical response, defined as an improvement of ≥8 points on the NIH Stroke Scale (83% vs 44%, p=0.002; adjusted OR=6.6; 95% CI 2.1–20.9). This association did not differ between patients treated within 6 hrs (OR = 6.4; 95% CI 1.5–27.8) and those treated beyond 6 hrs after symptom onset (OR = 13.7; 95% CI 1.4–140). Interpretation The robust association between endovascular reperfusion and good outcome among patients with the CT perfusion target mismatch profile treated up to 18 hours after symptom onset supports a randomized trial of endovascular therapy in this patient population.

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Section: Discussionmentioning

confidence: 94%

“…[10] These findings suggest that patient selection criteria will play a key role in determining the outcome of endovascular thrombectomy trials in the extended time-window.…”

Section: Introductionmentioning

confidence: 99%

Computed tomographic perfusion to Predict Response to Recanalization in ischemic stroke

Lansberg

Christensen

Kemp

et al. 2017

Annals of Neurology

Self Cite

116

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“…Furthermore, the positive association between reperfusion, favorable clinical response, and attenuation of infarct growth did not diminish in DEFUSE 2 patients with target mismatch who were treated up to 6–12 h after symptom onset. 25 …”

Section: Discussionmentioning

confidence: 99%

A multicenter randomized controlled trial of endovascular therapy following imaging evaluation for ischemic stroke (DEFUSE 3)

Albers

Lansberg

Kemp

et al. 2017

International Journal of Stroke

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245

196

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Rationale Early reperfusion in patients experiencing acute ischemic stroke is effective in patients with large vessel occlusion. No randomized data are available regarding the safety and efficacy of endovascular therapy beyond 6 h from symptom onset. Aim The aim of the study is to demonstrate that, among patients with large vessel anterior circulation occlusion who have a favorable imaging profile on computed tomography perfusion or magnetic resonance imaging, endovascular therapy with a Food and Drug Administration 510 K-cleared mechanical thrombectomy device reduces the degree of disability three months post stroke. Design The study is a prospective, randomized, multicenter, phase III, adaptive, blinded endpoint, controlled trial. A maximum of 476 patients will be randomized and treated between 6 and 16 h of symptom onset. Procedures Patients undergo imaging with computed tomography perfusion or magnetic resonance diffusion/perfusion, and automated software (RAPID) determines if the Target Mismatch Profile is present. Patients who meet both clinical and imaging selection criteria are randomized 1:1 to endovascular therapy plus medical management or medical management alone. The individual endovascular therapist chooses the specific device (or devices) employed. Study outcomes The primary endpoint is the distribution of scores on the modified Rankin Scale at day 90. The secondary endpoint is the proportion of patients with modified Rankin Scale 0–2 at day 90 (indicating functional independence). Analysis Statistical analysis for the primary endpoint will be conducted using a normal approximation of the Wilcoxon–Mann–Whitney test (the generalized likelihood ratio test).

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“…EST has been shown to benefit patients presenting beyond the established time window thereby biasing the results towards the null hypothesis. 29 …”

Section: Discussionmentioning

confidence: 99%

Time to Presentation Is Associated with Clinical Outcome in Hemispheric Stroke Patients Deemed Ineligible for Recanalization Therapy

Mayasi

Helenius

Goddeau

et al. 2016

Journal of Stroke and Cerebrovascular Diseases

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Background Delayed thrombolysis adversely impacts functional outcome after stroke. Therefore, great efforts are undertaken to reduce delay in patient presentation and initiate treatment as quickly as possible. However, little is known regarding the impact of time to presentation (TTP) on outcome in patients that are ineligible for acute stroke therapy. Thus, we sought to determine whether the TTP is associated with the 90-day outcome irrespective of eligibility for acute recanalization therapy. Methods We retrospectively analyzed 258 consecutive acute ischemic stroke patients evaluated between January 2013 and February 2014. Multivariable logistic regression was used to determine whether a greater TTP is independently associated with a poor 90-day outcome as defined as a modified Rankin scale (mRS) score of 3–6. Results In unadjusted analyses the TTP was inversely correlated with transfer from an acute facility (r=−.126, P=0.043), cardioembolic stroke etiology (r=−.146, P=0.019), and acute recanalization therapy (r=.−412, P<0.001). Conversely, a longer TTP correlated with a worse 90-day mRS (r=.127, P=0.045). After adjustment, the TTP (P=0.019), age (P<0.001), female sex (P=0.001), National Institute of Health Stroke Scale score (P<0.001), pre-admission mRS (P=0.001), atrial fibrillation (P<0.001), and infarct volume (P<0.001) were independently associated with a poor 90-day outcome. Importantly, a longer TTP (OR 1.016; 95%-CI 1.001 to 1.032; P=0.036) remained independently associated with the 90-day outcome when we restricted analyses to patients ineligible for acute intravenous and endovascular recanalization therapies. Conclusions Each hour delay in the TTP decreased chances for good outcome by approximately 2% independent of patient eligibility for acute recanalization therapies.

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Response to endovascular reperfusion is not time-dependent in patients with salvageable tissue

Cited by 87 publications

References 27 publications

Computed tomographic perfusion to Predict Response to Recanalization in ischemic stroke

Computed tomographic perfusion to Predict Response to Recanalization in ischemic stroke

A multicenter randomized controlled trial of endovascular therapy following imaging evaluation for ischemic stroke (DEFUSE 3)

Time to Presentation Is Associated with Clinical Outcome in Hemispheric Stroke Patients Deemed Ineligible for Recanalization Therapy

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