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Background: The use of advanced brain imaging to identify potentially salvageable ischemic penumbra has been controversial. We examined the effect of reperfusion on functional outcome in the EXTEND-IA trial. Method(s): Patients receiving tPA < 4.5 h with major vessel occlusion were randomized to thrombectomy versus tPA-only if CT-perfusion demonstrated mismatch ratio > 1.2 between hypoperfused tissue (Tmax > 6 s) and irreversibly injured ischemic core (relative cerebral blood flow < 30%), absolute mismatch > 10 mL and ischemic core < 70 mL (RAPID software, Stanford University). Reperfusion was defined as >90% reduction in Tmax > 6 s hypoperfusion volume between baseline and 24 h perfusion imaging. Modified Rankin Scale (mRS) was assessed at 90 days. Result(s): There were 70 patients, 35 in each arm, mean age 69, median NIHSS 15. Reperfusion of >90% of the affected territory occurred in 89% endovascular patients and 34% tPA-only patients (p < 0.001). Reperfusion was associated with independence (mRS0-2) in 72% versus 30% nonreperfused patients (p < 0.001). In ordinal analysis which assesses shift between individual levels of the mRS, the unadjusted generalized odds ratio = 4.5, 95%CI 2.2-9.0, p < 0.001 with a 'number needed to reperfuse' of 1.6 patients to achieve at least 1 point improvement on the mRS (OR = 5.1, p < 0.001, adjusted for age and NIHSS). Conclusion(s): In ischemic stroke patients with large vessel occlusion and 'target mismatch' indicating salvageable tissue on CT-perfusion, outcomes are usually unfavorable unless reperfusion is achieved with 70% of patients dead or dependent at 3 months. This is consistent with the penumbral hypothesis that, in the absence of reperfusion, penumbral tissue is recruited into the irreversibly injured infarct over time.

Background: Optimal imaging selection for endovascular therapy for ischemic stroke remains controversial with a range of criteria used in the recent positive trials. Large volume severe hypoperfusion (Tmax > 10 s) is one such criterion, with optimal threshold > 82 mL ('malignant profile'), in a previous study. We examined whether this was associated with poor response to reperfusion in the EXTEND-IA randomized trial, which did not exclude patients on this basis. Method(s): Patients receiving tPA < 4.5 h with major vessel occlusion and favorable CT-perfusion (CTP) were randomized (after written informed consent, IRB-approved) to thrombectomy after tPA versus tPA-alone. CTP eligibility required mismatch ratio > 1.2 between hypoperfused tissue (Tmax > 6 s) and irreversibly injured ischemic core (relative cerebral blood flow < 30%), absolute mismatch > 10 mL, ischemic core <70 mL (RAPID software, Stanford University). Tmax > 10 s volume was calculated and effect on clinical outcomes examined. Result(s): There were 70 patients, 35 in each arm, mean age = 69, median NIHSS = 15. In these patients with ischemic core < 70 mL, median Tmax > 10 s volume was 41 ml with 12/70(17%) > 82 ml, 6/70(8.6%) > 100 ml. Of the 'malignant' patients(Tmax10 s > 82 ml), 6/12(50%) had >90% reperfusion at 24 h (4 endovascular and 2 tPAonly), all of whom had 'early neurological recovery' (>=8 point NIHSS reduction or 0-1 by day 3) and 5/6(83%) had 90 day mRS0-1. No patient with <90% reperfusion had day 90 mRS < 3. Conclusion(s): In ischemic stroke patients <4.5 h after onset, large Tmax > 10 s volume in the absence of a large ischemic core was uncommon. Although the numbers in this study were small, the 83% rate of excellent functional outcome after reperfusion suggests that excluding such patients from therapy may not be justified.

Background: Recent trials have demonstrated improved outcomes with endovascular therapy for ischemic stroke compared with tPA. We examined the effects on resource utilization, length of stay and cost in the EXTEND-IA trial. Method(s): Patients receiving tPA < 4.5 h who had major vessel occlusion and CT-perfusion evidence of salvageable brain tissue were randomized to endovascular thrombectomy after tPA versus tPA-alone. Length of stay in acute inpatient, rehabilitation and nursing care units over the first 3 months and costs were compared between groups (Wilcoxon test) and the mean values were used to calculate costs for the average patient in each treatment group. Result(s): There were 70 patients, 35 in each arm, mean age 69, median NIHSS 15. Endovascular patients had shorter acute inpatient stays (mean 8 versus 12 days, p = 0.04) without increased time in intensive care (9 versus 11 hours, p = 0.51). Survivors spent less time in rehabilitation after endovascular treatment (mean 14 versus 33 days, p = 0.03). The cost of inpatient care in the first 3 months was similar for endovascular and tPA-only patients (mean AU$43,000 versus AU$45,000, respectively), including the AU$20,000 average cost for the thrombectomy. Ongoing nursing care (AU$146,000 p.a.) was required for 5/35 patients (all tPA-only). Conclusion(s): In ischemic stroke patients with large vessel occlusion and salvageable tissue on CT-perfusion, thrombectomy reduced length of stay and was cost neutral compared with tPA-alone over 3months. The healtheconomic benefits would be expected to increase further over time. The magnitude of difference in inpatient care costs suggests this finding would generalize to other health systems.

Background: The use of advanced brain imaging to identify potentially salvageable ischemic penumbra has been controversial. We examined the effect of reperfusion on functional outcome in the EXTEND-IA trial. Method(s): Patients receiving tPA < 4.5 h with major vessel occlusion were randomized to thrombectomy versus tPA-only if CT-perfusion demonstrated mismatch ratio > 1.2 between hypoperfused tissue (Tmax > 6 s) and irreversibly injured ischemic core (relative cerebral blood flow < 30%), absolute mismatch > 10 mL and ischemic core < 70 mL (RAPID software, Stanford University). Reperfusion was defined as >90% reduction in Tmax > 6 s hypoperfusion volume between baseline and 24 h perfusion imaging. Modified Rankin Scale (mRS) was assessed at 90 days. Result(s): There were 70 patients, 35 in each arm, mean age 69, median NIHSS 15. Reperfusion of >90% of the affected territory occurred in 89% endovascular patients and 34% tPA-only patients (p < 0.001). Reperfusion was associated with independence (mRS0-2) in 72% versus 30% nonreperfused patients (p < 0.001). In ordinal analysis which assesses shift between individual levels of the mRS, the unadjusted generalized odds ratio = 4.5, 95%CI 2.2-9.0, p < 0.001 with a 'number needed to reperfuse' of 1.6 patients to achieve at least 1 point improvement on the mRS (OR = 5.1, p < 0.001, adjusted for age and NIHSS). Conclusion(s): In ischemic stroke patients with large vessel occlusion and 'target mismatch' indicating salvageable tissue on CT-perfusion, outcomes are usually unfavorable unless reperfusion is achieved with 70% of patients dead or dependent at 3 months. This is consistent with the penumbral hypothesis that, in the absence of reperfusion, penumbral tissue is recruited into the irreversibly injured infarct over time.

Background: Optimal imaging selection for endovascular therapy for ischemic stroke remains controversial with a range of criteria used in the recent positive trials. Large volume severe hypoperfusion (Tmax > 10 s) is one such criterion, with optimal threshold > 82 mL ('malignant profile'), in a previous study. We examined whether this was associated with poor response to reperfusion in the EXTEND-IA randomized trial, which did not exclude patients on this basis. Method(s): Patients receiving tPA < 4.5 h with major vessel occlusion and favorable CT-perfusion (CTP) were randomized (after written informed consent, IRB-approved) to thrombectomy after tPA versus tPA-alone. CTP eligibility required mismatch ratio > 1.2 between hypoperfused tissue (Tmax > 6 s) and irreversibly injured ischemic core (relative cerebral blood flow < 30%), absolute mismatch > 10 mL, ischemic core <70 mL (RAPID software, Stanford University). Tmax > 10 s volume was calculated and effect on clinical outcomes examined. Result(s): There were 70 patients, 35 in each arm, mean age = 69, median NIHSS = 15. In these patients with ischemic core < 70 mL, median Tmax > 10 s volume was 41 ml with 12/70(17%) > 82 ml, 6/70(8.6%) > 100 ml. Of the 'malignant' patients(Tmax10 s > 82 ml), 6/12(50%) had >90% reperfusion at 24 h (4 endovascular and 2 tPAonly), all of whom had 'early neurological recovery' (>=8 point NIHSS reduction or 0-1 by day 3) and 5/6(83%) had 90 day mRS0-1. No patient with <90% reperfusion had day 90 mRS < 3. Conclusion(s): In ischemic stroke patients <4.5 h after onset, large Tmax > 10 s volume in the absence of a large ischemic core was uncommon. Although the numbers in this study were small, the 83% rate of excellent functional outcome after reperfusion suggests that excluding such patients from therapy may not be justified.

Background: Recent trials have demonstrated improved outcomes with endovascular therapy for ischemic stroke compared with tPA. We examined the effects on resource utilization, length of stay and cost in the EXTEND-IA trial. Method(s): Patients receiving tPA < 4.5 h who had major vessel occlusion and CT-perfusion evidence of salvageable brain tissue were randomized to endovascular thrombectomy after tPA versus tPA-alone. Length of stay in acute inpatient, rehabilitation and nursing care units over the first 3 months and costs were compared between groups (Wilcoxon test) and the mean values were used to calculate costs for the average patient in each treatment group. Result(s): There were 70 patients, 35 in each arm, mean age 69, median NIHSS 15. Endovascular patients had shorter acute inpatient stays (mean 8 versus 12 days, p = 0.04) without increased time in intensive care (9 versus 11 hours, p = 0.51). Survivors spent less time in rehabilitation after endovascular treatment (mean 14 versus 33 days, p = 0.03). The cost of inpatient care in the first 3 months was similar for endovascular and tPA-only patients (mean AU$43,000 versus AU$45,000, respectively), including the AU$20,000 average cost for the thrombectomy. Ongoing nursing care (AU$146,000 p.a.) was required for 5/35 patients (all tPA-only). Conclusion(s): In ischemic stroke patients with large vessel occlusion and salvageable tissue on CT-perfusion, thrombectomy reduced length of stay and was cost neutral compared with tPA-alone over 3months. The healtheconomic benefits would be expected to increase further over time. The magnitude of difference in inpatient care costs suggests this finding would generalize to other health systems.