Health budget implications of mechanical thrombectomy for acute ischaemic stroke in Australia.

INTRODUCTION: This research evaluates the budget impact of treating acute ischaemic stroke (AIS) using a combination of mechanical thrombectomy (MT) with stent retrievers (SR) and intravenous tissue-plasminogen activator (IV-tPA) in Australia. METHODS: This study examined the economic impact over five years for a patient cohort based on the number of patients treated with MT+ IV-tPA in Australia 2021, versus treatment with IV-tPA alone. A budget impact (BI) model was developed to project direct medical costs (economic impact) of IV-tPA+ MT with SR vs. Intravenous tissue-plasminogen activator alone over a five-year period (2021-2025 inclusive) from a healthcare perspective. The model is composed of a short-run decision tree model based on a 3-month post-treatment modified Rankin Scale (mRS) from the EXTEND-IA study and a published long-run Markov state transition model. Acute, mid-term and long-term care costs were projected based on anticipated mRS scores from the EXTEND-IA trial. Estimated yearly and cumulative budget impact were reported to indicate the economic impact of the two treatment strategies for AIS in the Australian healthcare system. RESULTS: MT+IV-tPA had a greater budgetary impact than IV-tPA alone, with annual savings starting at Year 1 and continuing through to Year 5. Cost savings of 21% or approximately $36 million can be achieved over five years for the patient cohort treated in Australia in 2021. Each MT procedure performed delivers approximately $3280 in annual health system savings per patient. CONCLUSION: Treatment of AIS with a combination of MT+IV-tPA generates significant savings in the Australian healthcare system compared with IV-tPA alone.

Transradial versus transfemoral access for diagnostic cerebral angiography: frequency of acute MRI findings in 500 consecutive patients at a single center.

BACKGROUND: The frequency of clinically symptomatic and asymptomatic diffusion-weighted imaging (DWI) hyperintense lesions and their correlation with the transradial artery (TRA) approach is unclear. OBJECTIVE: To assess the frequency of abnormal diffusion restriction foci on DWI following cerebral angiography (digital subtraction angiography (DSA)) with the TRA or transfemoral artery (TFA) approach and identify predictors of DWI restriction foci. METHODS: We analysed data from consecutive diagnostic cerebral angiograms obtained between January 2021 and October 2023 at a single tertiary center. MRI DWI was performed 2 hours after DSA. Patients underwent neurological assessment periprocedurally, as well as prior to discharge. RESULTS: 500 patients were analysed; 277 (55%) procedures were performed via TRA and 223 (45%) via TFA. Overall, 74 (14.8%) patients had abnormal findings in the postprocedure MRI DWI. A higher incidence of positive DWI findings was noted in the TRA group, with 46 (16.6%) patients, compared with 28 (12.6%) in the TFA group (P=0.21). Symptomatic events occurred in seven (2.5%) of the TRA group and in two (0.9%) of the TFA cohort (P=0.31). At 60 days, the neurological deficit rate was one (0.4%) for the TRA group and one (0.4%) for the TFA group. Procedure time was the only significant predictor of DWI restriction (OR=1.04 per minute; P=0.0001). CONCLUSION: Although there were more symptomatic or asymptomatic embolic events with TRA than with the TFA approach following elective cerebral angiography, this was not significantly different. We recommend the choice of vascular access based on patient anatomy and characteristics, aimed at improving care through enhanced safety.

Vanguard Study: Initial experience with the new fourth generation Pipeline Vantage Flow Diverter (PVFD): 6-month results, technical and clinical considerations.

BACKGROUND: The Pipeline Embolization Device has proven to be a safe and effective device for the treatment of intracranial aneurysms. The Pipeline Vantage Flow Diverter (PVFD) with Shield Technology is the new fourth generation of this implant, with modifications made compared to previous iterations. We aimed to evaluate the mechanical properties and clinical safety and efficacy of this device. METHODS: Vanguard is a single arm, single center, prospective study. Between April 2021 and April 2023, all consecutive patients with an unruptured aneurysm treated with Pipeline Vantage flow-diverting stents were included. There were no aneurysm size or location exclusion criteria. Safety (neurological serious adverse events) and efficacy (device deployment and aneurysm occlusion) were independently reviewed. Imaging follow-up data, and immediate, early (<30 days), and delayed (>30 days) neurological serious adverse events were independently assessed. RESULTS: 101 consecutive patients with a total of 115 aneurysms were included. The aneurysms were situated in the anterior (90.4%) or posterior (9.6%) circulations. A total of 124 devices were implanted. The deployment success rate was 100%. In four (4.0%) cases post-deployment angioplasty was required to optimize device wall apposition. Occlusion rates at 1 month were 54.7%, at 3 months 72.1%, and at 6 months 81.7%. Morbidity and mortality were 4.9% and 0%, respectively, at 6 months. Eight cases (6.9%) demonstrated in-stent stenosis, four of which had 'fish mouth' deformity. CONCLUSION: Initial results of the new generation PVFD for unruptured intracranial aneurysm treatment demonstrate overall satisfactory device performance, safety profile, and effectiveness.

Safety and efficacy of adjunctive intra-arterial antithrombotic therapy during endovascular thrombectomy for acute ischemic stroke: a systematic review and meta-analysis.

BACKGROUND: Half of patients who achieve successful recanalization following endovascular thrombectomy (EVT) for acute ischemic stroke experience poor functional outcome. We aim to investigate whether the use of adjunctive intra-arterial antithrombotic therapy (AAT) during EVT is safe and efficacious compared with standard therapy (ST) of EVT with or without prior intravenous thrombolysis. METHODS: Electronic databases were searched (PubMed/MEDLINE, Embase, Cochrane Library) from 2010 until October 2023. Data were pooled using a random-effects model and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Risk of bias was assessed using ROBINS-I and ROB-2. The primary outcome was functional independence (modified Rankin Scale (mRS) 0-2) at 3 months. Secondary outcomes were successful recanalization (modified Thrombolysis In Cerebral Infarction (TICI) 2b-3), symptomatic intracranial hemorrhage (sICH), and 90-day mortality. RESULTS: 41 randomized and non-randomized studies met the eligibility criteria. Overall, 15 316 patients were included; 3296 patients were treated with AAT during EVT and 12 020 were treated with ST alone. Compared with ST, patients treated with AAT demonstrated higher odds of functional independence (46.5% AAT vs 42.6% ST; OR 1.22, 95% CI 1.07 to 1.40, P=0.004, I2=48%) and a lower likelihood of 90-day mortality (OR 0.71, 95% CI 0.61 to 0.83, P<0.0001, I2=20%). The rates of sICH (OR 1.00, 95% CI 0.82 to 1.22,P=0.97, I2=13%) and successful recanalization (OR 1.09, 95% CI 0.84 to 1.42, P=0.52, I2=76%) were not significantly different. CONCLUSION: The use of AAT during EVT may improve functional outcomes and reduce mortality rates compared with ST alone, without an increased risk of sICH. These findings should be interpreted with caution pending the results from ongoing phase III trials to establish the efficacy and safety of AAT during EVT.

Evaluation of effectiveness and safety of the CorPath GRX robotic system in endovascular embolization procedures of cerebral aneurysms.

BACKGROUND: Robotic-assisted neurointervention was recently introduced, with implications that it could be used to treat neurovascular diseases. OBJECTIVE: To evaluate the effectiveness and safety of the robotic-assisted platform CorPath GRX for treating cerebral aneurysms. METHODS: This prospective, international, multicenter study enrolled patients with brain aneurysms that required endovascular coiling and/or stent-assisted coiling. The primary effectiveness endpoint was defined as successful completion of the robotic-assisted endovascular procedure without any unplanned conversion to manual treatment with guidewire or microcatheter navigation, embolization coil(s) or intracranial stent(s) deployment, or an inability to navigate vessel anatomy. The primary safety endpoint included intraprocedural and periprocedural events. RESULTS: The study enrolled 117 patients (74.4% female) with mean age of 56.6 years from 10 international sites,. Headache was the most common presenting symptom in 40/117 (34.2%) subjects. Internal carotid artery was the most common location (34/122, 27.9%), and the mean aneurysm height and neck width were 5.7±2.6 mm and 3.5±1.4 mm, respectively. The overall procedure time was 117.3±47.3 min with 59.4±32.6 min robotic procedure time. Primary effectiveness was achieved in 110/117 (94%) subjects with seven subjects requiring conversion to manual for procedure completion. Only four primary safety events were recorded with two intraprocedural aneurysm ruptures and two strokes. A Raymond-Roy Classification Scale score of 1 was achieved in 71/110 (64.5%) subjects, and all subjects were discharged with a modified Rankin Scale score of ≤2. CONCLUSIONS: This first-of-its-kind robotic-assisted neurovascular trial demonstrates the effectiveness and safety of the CorPath GRX System for endovascular embolization of cerebral aneurysm procedures. TRIAL REGISTRATION NUMBER: NCT04236856.

The Aristotle 18 and 24 microwires in neuroIntervention: Early experience at a single centre.

BACKGROUND: Current neurointerventional procedures are expanding the use of large bore microcatheters, of up to 0.033" inner diameters, to accommodate intrasaccular flow disruptors or neck-bridging devices, including flow diverters. The use of large bore microwires may mitigate the ledge gap between wire and catheter, facilitate navigation and offer support in distal tortuous anatomy. We aim to report our early experience using the novel Aristotle (Scientia Vascular, West Valley City, UT) 18 and 24 microwires in neurovascular interventions. METHODS: We analysed neurointerventional procedures in which the Aristotle 18 and 24 microwires were used at a single centre. Prospectively collected data, from March 2022 to February 2023, including patient's clinical outcome (successful target vessel, aneurysm catheterisation, peri-procedural complications (thromboembolic, haemorrhagic, vessel dissection or perforation) were analysed. RESULTS: Overall, the use of Aristotle 18 and 24 microwires was recorded in 84 neurointerventional procedures during the study period, including endovascular aneurysm treatment (n = 30), endovascular thrombectomy (n = 46), dural venous sinus manometry/stent placement (n = 7), and extracranial carotid artery stent placement (n = 1). The Aristotle 18 microwire was used in conjunction with 0.021" microcatheters and the Aristotle 24 microwire with the 0.027 or 0.033" microcatheters. In all cases (100%), the target vessel or aneurysm was reached with the microwire, allowing seamless advancement of the selected microcatheters. No procedure related complications were recorded. CONCLUSIONS: The use of the Aristotle 18 and 24 microwires in neurointerventional procedures is feasible and safe. The microwires provide reduced ledge gap, improved torquability, support and safety over standard 0.014" microwires.

World federation of interventional and therapeutic neuroradiology (WFITN) federation assembly neurointerventional surgery safety checklist.

Over the last 10 years, there has been a rise in neurointerventional case complexity, device variety and physician distractions. Even among experienced physicians, this trend challenges our memory and concentration, making it more difficult to remember safety principles and their implications. Checklists are regarded by some as a redundant exercise that wastes time, or as an attack on physician autonomy. However, given the increasing case and disease complexity along with the number of distractions, it is even more important now to have a compelling reminder of safety principles that preserve habits that are susceptible to being overlooked because they seem mundane. Most hospitals have mandated a pre-procedure neurointerventional time-out checklist, but often it ends up being done in a cursory fashion for the primary purpose of 'checking off boxes'. There may be value in iterating the checklist to further emphasize safety and communication. The Federation Assembly of the World Federation of Interventional and Therapeutic Neuroradiology (WFITN) decided to construct a checklist for neurointerventional cases based on a review of the literature and insights from an expert panel.

A comparison of antiplatelet therapy during the peri- and post-operative periods following flow-diverting stent insertion for unruptured intracranial aneurysms: A systematic review.

BACKGROUND: Flow diverters (FDs) are neuroendovascular stents indicated for the management of unruptured intracranial aneurysms. Due to their composition, dual antiplatelet therapy (DAPT) is essential during the peri- and post-operative periods to prevent thromboembolic events. However, there is limited consensus within the scientific community regarding which antiplatelets to use and dosing following neuroendovascular treatment of aneurysms. METHOD: A systematic search of four electronic databases was conducted during November 2020 that included studies published between January 2010 and November 2020. Eligibility for inclusion included primary research articles, published in the English language and use of flow-diverting intracranial stents. Studies were excluded if they utilised combined therapies (e.g. FD with stent-assisted coiling), animal studies, clinical trial protocols and study population of less than 10 subjects. RESULTS: Eighteen studies were identified for inclusion with a total of 1312 patients with 1355 unruptured intracranial aneurysms treated with FDs. Of these, 13 studies primarily investigated the use of clopidogrel with aspirin with low rates of haemorrhagic and thromboembolic complications. A forest plot of nine of these studies showed average efficacy of 88% at 95% confidence interval (CI) (SD + 5%) with 63% heterogeneity. CONCLUSIONS: The large proportion of studies investigating clopidogrel and aspirin antiplatelet therapy presents a challenge in comparing antiplatelet regimens. Although prasugrel and ticagrelor have been identified as suitable alternatives to clopidogrel, these were based on studies with small cohort sizes. Glycoprotein IIb/IIIa inhibitors may be efficacious as rescue therapy for intra-procedural thrombosis. Further research is required to determine which antiplatelet is most suitable.

Ultra-Long Transfers for Endovascular Thrombectomy-Mission Impossible?: The Australia-New Zealand Experience.

BACKGROUND: Endovascular thrombectomy (EVT) access in remote areas is limited. Preliminary data suggest that long distance transfers for EVT may be beneficial; however, the magnitude and best imaging strategy at the referring center remains uncertain. We hypothesized that patients transferred >300 miles would benefit from EVT, achieving rates of functional independence (modified Rankin Scale [mRS] score of 0-2) at 3 months similar to those patients treated at the comprehensive stroke center in the randomized EVT extended window trials and that the selection of patients with computed tomography perfusion (CTP) at the referring site would be associated with ordinal shift toward better outcomes on the mRS. METHODS: This is a retrospective analysis of patients transferred from 31 referring hospitals >300 miles (measured by the most direct road distance) to 9 comprehensive stroke centers in Australia and New Zealand for EVT consideration (April 2016 through May 2021). RESULTS: There were 131 patients; the median age was 64 [53-74] years and the median baseline National Institutes of Health Stroke Scale score was 16 [12-22]. At baseline, 79 patients (60.3%) had noncontrast CT+CT angiography, 52 (39.7%) also had CTP. At the comprehensive stroke center, 114 (87%) patients underwent cerebral angiography, and 96 (73.3%) proceeded to EVT. At 3 months, 62 patients (48.4%) had an mRS score of 0 to 2 and 81 (63.3%) mRS score of 0 to 3. CTP selection at the referring site was not associated with better ordinal scores on the mRS at 3 months (mRS median of 2 [1-3] versus 3 [1-6] in the patients selected with noncontrast CT+CT angiography, P=0.1). Nevertheless, patients selected with CTP were less likely to have an mRS score of 5 to 6 (odds ratio 0.03 [0.01-0.19]; P<0.01). CONCLUSIONS: In selected patients transferred >300 miles, there was a benefit for EVT, with outcomes similar to those treated in the comprehensive stroke center in the EVT extended window trials. Remote hospital CTP selection was not associated with ordinal mRS improvement, but was associated with fewer very poor 3-month outcomes.

Transradial versus transfemoral arterial approach for cerebral angiography and the frequency of embolic events on diffusion weighted MRI.

BACKGROUND: The radial artery approach has become popular as a 'radial first' strategy for arterial access in neuroangiography and neurointerventions. Recent studies have shown that transradial arterial access (TRA) for cerebral angiography has been associated with reduced access site complication rates and improved patient satisfaction compared with transfemoral access (TFA). The goal of this study was to evaluate the presence of abnormal MRI diffusion weighted imaging (DWI) foci following DSA and correlate their frequency with TRA or TFA. METHODS: We prospective analyzed 200 consecutive adult DSAs performed from January 2021 to January 2022, at a single tertiary center. RESULTS: Of the 200 consecutive diagnostic cerebral angiograms, 51% were performed via TRA and 49% were performed via TFA. Of the TRA cerebral angiograms, 17.5% demonstrated at least one hyperintense focus on MRI DWI. Of the TFA procedures, 5.2% were considered positive. One patient (0.5%) in the TRA group experienced a minor neurologic deficit postoperatively that had not completely resolved at 90 days after the procedure and no neurologic deficits occurred in the TFA group. CONCLUSIONS: Despite the proven benefit of TRA over TFA in neurointervention, the number of MRI DWI restriction foci were significantly more frequent during cerebral angiography when TRA was selected. Although the number of clinically symptomatic events were minimal, the widespread use of the technique may become clinically relevant. Further studies contrasting the TRA and TFA techniques will be beneficial for cerebral angiography.

Aspiration technique for percutaneous endovascular retrieval of contraceptive device embolized to the pulmonary vasculature.

Contraceptive implant migration into the pulmonary circulation is an uncommon, but potentially serious complication. We describe an "aspiration" technique for percutaneous retrieval of a contraceptive implant from a subsegmental pulmonary artery, using a Penumbra Neuron MAX 088 guiding catheter and a Merit Medical VacLok Vacuum Pressure Syringe, as an alternative to the previously described snare technique. Our patient had an uneventful recovery and was discharged home on the same day.

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.

First clinical experience with the new Surpass Evolve flow diverter: technical and clinical considerations.

OBJECTIVE: To describe the results in patients treated with the Surpass Evolve (SE) device, the new generation of Surpass flow diverters. METHODS: Twenty-five consecutive patients (20 women, average age 58 years), with anterior or posterior circulation aneurysms treated with SEs in two early-user centers, were included. Device properties and related technical properties, imaging and clinical follow-up data, and intraprocedural, early (<30 days) and delayed (>30 days) neurological complications, further divided into minor (silent/non-permanent) and major (permanent) complications, were recorded and analyzed. RESULTS: Twenty-nine SEs were successfully implanted in all subjects to treat 26 aneurysms using an 0.027" microcatheter with an average of 1.2 stents per patient. No intraprocedural thromboembolic or hemorrhagic complications were seen. At clinical follow-up, 24/25 (96%) patients had a modified Rankin Score of 0-2. Mortality was 0%. Imaging follow-up, available in 22/25 (88%) patients (median follow-up time 4 months), showed a complete aneurysm occlusion in 13/23 (57%) imaged lesions. Minor, transitory neurological deficits were recorded in 5/25 (20%) patients. One (4%) major complication was seen in one patient (4%) with a left-sided hemispheric stroke on postprocedural day 4 due to an acute stent thrombosis. CONCLUSIONS: Preliminary experience in patients demonstrates a good performance of the SE. This newly designed implant maintains the engineering characteristics of Surpass flow diverters, including precise placement due to its lower foreshortening and a high mesh density, yet can be deployed through a significantly lower-profile delivery system.

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 .).

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.

Endovascular Thrombectomy for Ischemic Stroke Increases Disability-Free Survival, Quality of Life, and Life Expectancy and Reduces Cost.

BACKGROUND: Endovascular thrombectomy improves functional outcome in large vessel occlusion ischemic stroke. We examined disability, quality of life, survival and acute care costs in the EXTEND-IA trial, which used CT-perfusion imaging selection. METHODS: Large vessel ischemic stroke patients with favorable CT-perfusion were randomized to endovascular thrombectomy after alteplase versus alteplase-only. Clinical outcome was prospectively measured using 90-day modified Rankin scale (mRS). Individual patient expected survival and net difference in Disability/Quality-adjusted life years (DALY/QALY) up to 15 years from stroke were modeled using age, sex, 90-day mRS, and utility scores. Level of care within the first 90 days was prospectively measured and used to estimate procedure and inpatient care costs (US$ reference year 2014). RESULTS: There were 70 patients, 35 in each arm, mean age 69, median NIHSS 15 (IQR 12-19). The median (IQR) disability-weighted utility score at 90 days was 0.65 (0.00-0.91) in the alteplase-only versus 0.91 (0.65-1.00) in the endovascular group (p = 0.005). Modeled life expectancy was greater in the endovascular versus alteplase-only group (median 15.6 versus 11.2 years, p = 0.02). The endovascular thrombectomy group had fewer simulated DALYs lost over 15 years [median (IQR) 5.5 (3.2-8.7) versus 8.9 (4.7-13.8), p = 0.02] and more QALY gained [median (IQR) 9.3 (4.2-13.1) versus 4.9 (0.3-8.5), p = 0.03]. Endovascular patients spent less time in hospital [median (IQR) 5 (3-11) days versus 8 (5-14) days, p = 0.04] and rehabilitation [median (IQR) 0 (0-28) versus 27 (0-65) days, p = 0.03]. The estimated inpatient costs in the first 90 days were less in the thrombectomy group (average US$15,689 versus US$30,569, p = 0.008) offsetting the costs of interhospital transport and the thrombectomy procedure (average US$10,515). The average saving per patient treated with thrombectomy was US$4,365. CONCLUSION: Thrombectomy patients with large vessel occlusion and salvageable tissue on CT-perfusion had reduced length of stay and overall costs to 90 days. There was evidence of clinically relevant improvement in long-term survival and quality of life. CLINICAL TRIAL REGISTRATION: http://www.ClinicalTrials.gov NCT01492725 (registered 20/11/2011).

Endovascular therapy for ischemic stroke with perfusion-imaging selection.

BACKGROUND: Trials of endovascular therapy for ischemic stroke have produced variable results. We conducted this study to test whether more advanced imaging selection, recently developed devices, and earlier intervention improve outcomes. METHODS: We randomly assigned patients with ischemic stroke who were receiving 0.9 mg of alteplase per kilogram of body weight less than 4.5 hours after the onset of ischemic stroke either to undergo endovascular thrombectomy with the Solitaire FR (Flow Restoration) stent retriever or to continue receiving alteplase alone. All the patients had occlusion of the internal carotid or middle cerebral artery and evidence of salvageable brain tissue and ischemic core of less than 70 ml on computed tomographic (CT) perfusion imaging. The coprimary outcomes were reperfusion at 24 hours and early neurologic improvement (≥8-point reduction on the National Institutes of Health Stroke Scale or a score of 0 or 1 at day 3). Secondary outcomes included the functional score on the modified Rankin scale at 90 days. RESULTS: The trial was stopped early because of efficacy after 70 patients had undergone randomization (35 patients in each group). The percentage of ischemic territory that had undergone reperfusion at 24 hours was greater in the endovascular-therapy group than in the alteplase-only group (median, 100% vs. 37%; P<0.001). Endovascular therapy, initiated at a median of 210 minutes after the onset of stroke, increased early neurologic improvement at 3 days (80% vs. 37%, P=0.002) and improved the functional outcome at 90 days, with more patients achieving functional independence (score of 0 to 2 on the modified Rankin scale, 71% vs. 40%; P=0.01). There were no significant differences in rates of death or symptomatic intracerebral hemorrhage. CONCLUSIONS: In patients with ischemic stroke with a proximal cerebral arterial occlusion and salvageable tissue on CT perfusion imaging, early thrombectomy with the Solitaire FR stent retriever, as compared with alteplase alone, improved reperfusion, early neurologic recovery, and functional outcome. (Funded by the Australian National Health and Medical Research Council and others; EXTEND-IA ClinicalTrials.gov number, NCT01492725, and Australian New Zealand Clinical Trials Registry number, ACTRN12611000969965.).