Clinical outcomes of delayed mechanical thrombectomy: Descriptive analysis and development of a screening tool.

BACKGROUND AND PURPOSE: Limited data guide the selection of patients with large vessel occlusion ischaemic stroke who may benefit from referral to a distant tertiary centre for mechanical thrombectomy (MT). We aimed to characterize this population, describe clinical outcomes and develop a screening system to identify patients most likely to benfit from delayed mechanical thrombectomy (MT). METHODS: We undertook a retrospective cohort analysis enrolling patients transferred from regional sites to one of two MT comprehensive stroke units with a time from non-contrast computed tomography (NCCT) of the brain to reperfusion of 4 h or more. We describe Alberta Stroke Programme Early Computed Tomography Score (ASPECTS), National Institute of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS) in our patients and compare these patients to those in extended-time-window trials. Lastly, we developed and validated a scoring model to help clinicians identify appropriate patients based on variables associated with poor outcomes. RESULTS: We included 563 patients, 46% of whom received thrombolysis; the median (interquartile range [IQR]) ASPECTS was 8 (7-10) and the median (IQR) NIHSS score was 16 (11-20). The median (IQR) symptom to mechanical reperfusion time was 390 (300-580) min. Eight patients (1%) had a symptomatic haemorrhage. We achieved good clinical outcome (defined as mRS score ≤2) in 299 patients (54%). Age, diabetes, NIHSS score and ASPECTS were used to create a weighted scoring system with a validated area under the curve of 0.83 (95% confidence interval 0.74-0.92). CONCLUSION: Our study shows, in highly selected patients, that delayed MT many hours after baseline NCCT is associated with good clinical outcomes. However, older patients with diabetes, high NIHSS score and low ASPECTS may not benefit from transfer to a hub centre many hours away for MT in this model of care.

Tenecteplase versus Alteplase before Thrombectomy for Ischemic Stroke.

BACKGROUND: Intravenous infusion of alteplase is used for thrombolysis before endovascular thrombectomy for ischemic stroke. Tenecteplase, which is more fibrin-specific and has longer activity than alteplase, is given as a bolus and may increase the incidence of vascular reperfusion. METHODS: We randomly assigned patients with ischemic stroke who had occlusion of the internal carotid, basilar, or middle cerebral artery and who were eligible to undergo thrombectomy to receive tenecteplase (at a dose of 0.25 mg per kilogram of body weight; maximum dose, 25 mg) or alteplase (at a dose of 0.9 mg per kilogram; maximum dose, 90 mg) within 4.5 hours after symptom onset. The primary outcome was reperfusion of greater than 50% of the involved ischemic territory or an absence of retrievable thrombus at the time of the initial angiographic assessment. Noninferiority of tenecteplase was tested, followed by superiority. Secondary outcomes included the modified Rankin scale score (on a scale from 0 [no neurologic deficit] to 6 [death]) at 90 days. Safety outcomes were death and symptomatic intracerebral hemorrhage. RESULTS: Of 202 patients enrolled, 101 were assigned to receive tenecteplase and 101 to receive alteplase. The primary outcome occurred in 22% of the patients treated with tenecteplase versus 10% of those treated with alteplase (incidence difference, 12 percentage points; 95% confidence interval [CI], 2 to 21; incidence ratio, 2.2; 95% CI, 1.1 to 4.4; P=0.002 for noninferiority; P=0.03 for superiority). Tenecteplase resulted in a better 90-day functional outcome than alteplase (median modified Rankin scale score, 2 vs. 3; common odds ratio, 1.7; 95% CI, 1.0 to 2.8; P=0.04). Symptomatic intracerebral hemorrhage occurred in 1% of the patients in each group. CONCLUSIONS: Tenecteplase before thrombectomy was associated with a higher incidence of reperfusion and better functional outcome than alteplase among patients with ischemic stroke treated within 4.5 hours after symptom onset. (Funded by the National Health and Medical Research Council of Australia and others; EXTEND-IA TNK ClinicalTrials.gov number, NCT02388061 .).

Endovascular Therapy for Ischemic Stroke Can Be Successfully Performed by Peripheral Vascular Interventionalists.

PURPOSE: To describe interventionalist and workflow characteristics of an acute stroke endovascular thrombectomy (EVT) center without a dedicated interventional neuroradiology service and report clinical and radiologic outcomes. MATERIALS AND METHODS: Retrospective review was performed of all patients receiving EVT at Christchurch Hospital, New Zealand, from June 2014 to the end of December 2019 from a prospective reperfusion registry. During the study period, 5 peripheral vascular interventional radiologists, 2 of whom had experience in other neuroendovascular procedures, performed 210 EVT procedures. Median age of patients was 76 years (interquartile range: 64-83 y), and 107 (51%) were men. RESULTS: The most commonly occluded vessel was the M1 middle cerebral artery (n = 114; 54%). Successful reperfusion (Modified Treatment In Cerebral Ischemia score 2b-3) was achieved in 180 (86%) procedures. Favorable 90-day outcome (modified Rankin Scale score 0-2) was achieved in 102 (54%) patients with no disability before stroke. Symptomatic intracranial hemorrhage occurred in 3 (1.4%) patients. Treatment rates in the local catchment area increased from 6 per 100,000 population in 2017 to 15 per 100,000 in 2019. CONCLUSIONS: The results of this study suggest peripheral vascular interventional radiologists with specific training can successfully perform EVT resulting in a significant increase in EVT provision.

Effect of Intravenous Tenecteplase Dose on Cerebral Reperfusion Before Thrombectomy in Patients With Large Vessel Occlusion Ischemic Stroke: The EXTEND-IA TNK Part 2 Randomized Clinical Trial.

Importance: Intravenous thrombolysis with tenecteplase improves reperfusion prior to endovascular thrombectomy for ischemic stroke compared with alteplase. Objective: To determine whether 0.40 mg/kg of tenecteplase safely improves reperfusion before endovascular thrombectomy vs 0.25 mg/kg of tenecteplase in patients with large vessel occlusion ischemic stroke. Design, Setting, and Participants: Randomized clinical trial at 27 hospitals in Australia and 1 in New Zealand using open-label treatment and blinded assessment of radiological and clinical outcomes. Patients were enrolled from December 2017 to July 2019 with follow-up until October 2019. Adult patients (N = 300) with ischemic stroke due to occlusion of the intracranial internal carotid, \basilar, or middle cerebral artery were included less than 4.5 hours after symptom onset using standard intravenous thrombolysis eligibility criteria. Interventions: Open-label tenecteplase at 0.40 mg/kg (maximum, 40 mg; n = 150) or 0.25 mg/kg (maximum, 25 mg; n = 150) given as a bolus before endovascular thrombectomy. Main Outcomes and Measures: The primary outcome was reperfusion of greater than 50% of the involved ischemic territory prior to thrombectomy, assessed by consensus of 2 blinded neuroradiologists. Prespecified secondary outcomes were level of disability at day 90 (modified Rankin Scale [mRS] score; range, 0-6); mRS score of 0 to 1 (freedom from disability) or no change from baseline at 90 days; mRS score of 0 to 2 (functional independence) or no change from baseline at 90 days; substantial neurological improvement at 3 days; symptomatic intracranial hemorrhage within 36 hours; and all-cause death. Results: All 300 patients who were randomized (mean age, 72.7 years; 141 [47%] women) completed the trial. The number of participants with greater than 50% reperfusion of the previously occluded vascular territory was 29 of 150 (19.3%) in the 0.40 mg/kg group vs 29 of 150 (19.3%) in the 0.25 mg/kg group (unadjusted risk difference, 0.0% [95% CI, -8.9% to -8.9%]; adjusted risk ratio, 1.03 [95% CI, 0.66-1.61]; P = .89). Among the 6 secondary outcomes, there were no significant differences in any of the 4 functional outcomes between the 0.40 mg/kg and 0.25 mg/kg groups nor in all-cause deaths (26 [17%] vs 22 [15%]; unadjusted risk difference, 2.7% [95% CI, -5.6% to 11.0%]) or symptomatic intracranial hemorrhage (7 [4.7%] vs 2 [1.3%]; unadjusted risk difference, 3.3% [95% CI, -0.5% to 7.2%]). Conclusions and Relevance: Among patients with large vessel occlusion ischemic stroke, a dose of 0.40 mg/kg, compared with 0.25 mg/kg, of tenecteplase did not significantly improve cerebral reperfusion prior to endovascular thrombectomy. The findings suggest that the 0.40-mg/kg dose of tenecteplase does not confer an advantage over the 0.25-mg/kg dose in patients with large vessel occlusion ischemic stroke in whom endovascular thrombectomy is planned. Trial Registration: ClinicalTrials.gov Identifier: NCT03340493.

Endovascular thrombectomy for acute ischaemic stroke improves and maintains function in the very elderly: A multicentre propensity score matched analysis.

Introduction: The very elderly (⩾80 years) are under-represented in randomised endovascular thrombectomy (EVT) clinical trials for acute ischaemic stroke. Rates of independent outcome in this group are generally lower than the less-old patients but the comparisons may be biased by an imbalance of non-age related baseline characteristics, treatment related metrics and medical risk factors. Patients and methods: We compared outcomes between very elderly (⩾80) and the less-old (<80 years) using retrospective data from consecutive patients receiving EVT from four comprehensive stroke centres in New Zealand and Australia. We used propensity score matching or multivariable logistic regression to account for confounders. Results: We included 600 patients (300 in each age cohort) after propensity score matching from an initial group of 1270 patients. The median baseline National Institutes of Health Stroke Scale was 16 (11-21), with 455 (75.8%) having symptom free pre-stroke independent function, and 268 (44.7%) receiving intravenous thrombolysis. Good functional outcome (90-day modified Rankin Scale 0-2) was achieved in 282 (46.8%), with very elderly patients having less proportion of good outcome compared to the less-old (118 (39.3%) vs 163 (54.3%), p < 0.01). There was no difference between the very elderly and the less-old in the proportion of patients who returned to baseline function at 90 days (56 (18.7%) vs 62 (20.7%), p = 0.54). All-cause 90-day mortality was higher in the very elderly (75 (25%) vs 49 (16.3%), p < 0.01), without a difference in symptomatic haemorrhage (very elderly 11 (3.7%) vs 6 (2.0%), p = 0.33). In the multivariable logistic regression models, the very elderly were significantly associated with reduced odds of good 90-day outcome (OR 0.49, 95% CI 0.34-0.69, p < 0.01) but not with return to baseline function (OR 0.85, 90% CI 0.54-1.29, p = 0.45) after adjusting for confounders. Conclusion: Endovascular thrombectomy can be successfully and safely performed in the very elderly. Despite an increase in all-cause 90-day mortality, selected very elderly patients are as likely as younger patients with similar baseline characteristics to return to baseline function following EVT.

Aspiration thrombectomy using a novel 088 catheter and specialized delivery catheter.

BACKGROUND: We describe the first-in-human experience using the Route 92 Medical Aspiration System to perform thrombectomy in the initial 45 consecutive stroke patients enrolled in the SUMMIT NZ trial. This aspiration system includes a specifically designed delivery catheter which enables delivery of 0.070 inch and 0.088 inch aspiration catheters. METHODS: The SUMMIT NZ trial is a prospective, multicenter, single-arm study with core lab imaging adjudication. Patients presenting with acute ischemic stroke from large vessel occlusion are eligible to enrol. The study has had three phases which transitioned from use of the 0.070 inch to the 0.088 inch catheter. RESULTS: Vessel occlusions were located in the internal carotid artery (27%), M1 (60%) and M2 (13%). Median baseline National Institutes of Health Stroke Scale (NIHSS) was 16 (IQR 10). Across the three phases, the first-pass reperfusion rate of modified Thrombolysis In Cerebral Infarction (mTICI) ≥2b was 62% using the Route 92 Medical system; this rate was 29% in phase 1, 56% in phase 2, and 80% in phase 3. The first-pass reperfusion rate of mTICI ≥2c was 42% overall, 29% in phase 1, 33% in phase 2, and 55% in phase 3. A final reperfusion rate of mTICI ≥2b was achieved in 96% of cases, with 36% of cases using adjunctive devices. Patients had an average improvement of 6.7 points in NIHSS from baseline at 24 hours, and at 90 days 48% were functionally independent (modified Rankin Scale 0-2). CONCLUSIONS: In this early experience, the Route 92 Medical Aspiration System has been effective and safe. The system has design features that improve catheter deliverability and have the potential to increase first-pass reperfusion rates in aspiration thrombectomy.

Endovascular clot retrieval for acute ischaemic stroke in New Zealand.

AIMS: Stroke endovascular clot retrieval (ECR) in patients with large proximal vessel occlusion improves clinical outcomes. We present the New Zealand ECR experience. METHODS: All New Zealand patients treated with ECR since 2011 were included. Patients were considered eligible if they were independent prior to stroke and had proximal intracranial arterial occlusion. RESULTS: Three hundred and twelve patients [136 women, mean (SD) age of 64 (17) years] from 11 district health boards have been treated between March 2011 and April 2018. There were 260 (83%) patients with anterior and 52 (17%) with posterior circulation arterial occlusion. One hundred and ninety-three (62%) patients were pre-treated with intravenous alteplase. The median time from symptom onset to groin puncture was 210 (range 65-985) minutes. Complete or near-complete recanalisation (Thrombolysis in Cerebral Infarction scores of 3 or 2b) was achieved in 260 of 300 (87%) and the National Institutes of Health Stroke Scale score improved from a median of 18 at baseline to 7 at 24 hours. By day 90, 55% of the anterior circulation patients and 40% of the posterior circulation patients were living independently at home. Mortality rates were 20% for anterior circulation patients and 30% for the posterior circulation patients. CONCLUSIONS: This study has shown that stroke endovascular clot retrieval is being provided safely and effectively in New Zealand. However, there remain discrepancies in service provision, and ongoing regional, inter-regional and inter-sector collaboration is essential to implement comprehensive and equitable ECR services across the country.

Tenecteplase versus alteplase before endovascular thrombectomy (EXTEND-IA TNK): A multicenter, randomized, controlled study.

Background and hypothesis Intravenous thrombolysis with alteplase remains standard care prior to thrombectomy for eligible patients within 4.5 h of ischemic stroke onset. However, alteplase only succeeds in reperfusing large vessel arterial occlusion prior to thrombectomy in a minority of patients. We hypothesized that tenecteplase is non-inferior to alteplase in achieving reperfusion at initial angiogram, when administered within 4.5 h of ischemic stroke onset, in patients planned to undergo endovascular therapy. Study design EXTEND-IA TNK is an investigator-initiated, phase II, multicenter, prospective, randomized, open-label, blinded-endpoint non-inferiority study. Eligibility requires a diagnosis of ischemic stroke within 4.5 h of stroke onset, pre-stroke modified Rankin Scale≤3 (no upper age limit), large vessel occlusion (internal carotid, basilar, or middle cerebral artery) on multimodal computed tomography and absence of contraindications to intravenous thrombolysis. Patients are randomized to either IV alteplase (0.9 mg/kg, max 90 mg) or tenecteplase (0.25 mg/kg, max 25 mg) prior to thrombectomy. Study outcomes The primary outcome measure is reperfusion on the initial catheter angiogram, assessed as modified treatment in cerebral infarction 2 b/3 or the absence of retrievable thrombus. Secondary outcomes include modified Rankin Scale at day 90 and favorable clinical response (reduction in National Institutes of Health Stroke Scale by ≥8 points or reaching 0-1) at day 3. Safety outcomes are death and symptomatic intracerebral hemorrhage. Trial registration ClinicalTrials.gov NCT02388061.

Prioritizing patients for elective surgery: a systematic review.

BACKGROUND: Priority scoring tools are moot as means for dealing with burgeoning elective surgical waiting lists. There is ongoing development work in New Zealand, Canada and the UK. This emerging international perspective is invaluable in determining the application of these tools and addressing any pitfalls. METHODS: A systematic electronic literature review was performed. Information was also retrieved using a search of reference lists of all papers included in the review and contact with those who were involved in the development of such criteria. RESULTS: The ethical basis of prioritization differed among priority scoring tools and in a number was not stated. The majority of tools covered criteria for specific procedures. Delphi consensus methods and regression were the predominant methods for -deter-mining -specific criteria. Authors' opinions were the main source of generic criteria. Linear and non-linear models or matrices sum-mated criteria. CONCLUSION: There is debate over the ethical basis for prioritization. It is a concern that it is not addressed in many studies. The development of generic criteria showed a dearth of consensus approaches that represents a significant gap in our knowledge. On the aspects of summation and weighting, the impact of assumptions on the prioritization of patients may not have been fully explored.