Benefit of Endovascular Thrombectomy by Mode of Onset: Secondary Analysis of the DAWN Trial
Abstract
Background and Purpose—
It is unknown whether the benefit of thrombectomy in late presenting acute stroke patients with imaging evidence of clinical-infarct mismatch is different in patients presenting with wake-up stroke compared with those presenting with witnessed onset or unwitnessed onset.
Methods—
Prespecified secondary analysis was performed from DAWN (Diffusion Weighted Imaging [DWI] or Computerized Tomography Perfusion [CTP] Assessment With Clinical Mismatch in the Triage of Wake Up and Late Presenting Strokes Undergoing Neurointervention), a multicenter, prospective, randomized clinical trial with blinded end point assessment comparing thrombectomy with the Trevo device against standard medical therapy in patients with acute stroke and clinical-infarct mismatch presenting 6 to 24 hour after the time last seen well. For the purposes of this study, the primary outcome was the proportion of modified Rankin Scale score 0 to 2 at 90 days. Univariable analysis and multivariable logistic regression was used to assess the relationship between outcome and mode of onset.
Results—
All 206 enrolled patients were included in the study. Mode of onset was: wake-up stroke (55.3%, n=114), witnessed onset (12.1%, n=25), and unwitnessed onset (32.5%, n=67) with median time last seen well to randomization (13.4±3.7, 10.0±3.7, 14.1±4.9 hours) respectively. Rates of 90-day modified Rankin Scale score of 0 to 2 and symptomatic intracerebral hemorrhage in the thrombectomy arm were not statistically different across patient onset subtypes (P=0.79 and P=0.40, respectively). The benefit of thrombectomy compared with best medical therapy was maintained across all 3 onset modes (rates of 90-day modified Rankin Scale score of 0 to 2 in patients allocated to thrombectomy versus control: wake-up stroke—49.3% versus 10.6%, witnessed onset—63.6% versus 21.4%, UW—41.4% versus 13.2%; P×interaction=0.79). In univariable and multivariable analyses, mode of onset was not identified as a significant predictor of modified Rankin Scale score 0 to 2 at 90 days.
Conclusions—
In patients with acute ischemic stroke presenting between 6 and 24 hours from time last seen well and harboring clinical-infarct mismatch, the benefit of thrombectomy was similar regardless of the wake-up, unwitnessed, or witnessed mode of onset.
Introduction
In the absence of reperfusion, acute ischemic stroke because of large vessel occlusion (LVO) has a dismal natural history.1–9 Although time represents a critical determinant of patient eligibility for reperfusion therapies, the time of symptom onset often times cannot be confirmed with precision because in many patients (including those who wake up with neurological deficits) the point in time at which neurological deficits first occur is unknown. There are 2 distinct symptom-based time points that can be used to gauge stroke onset: time symptoms first observed and time last seen well.10 For the purposes of determining eligibility for reperfusion therapies (intravenous or intra-arterial), the latter is widely accepted as a reference point and has been used in all major acute stroke reperfusion trials. These time markers are applied to the 3 distinct modes by which patient stroke symptoms first come to attention: (1) wake up stroke (WUS— patients who were normal before going to sleep and had their deficit first observed immediately upon awakening); (2) unwitnessed onset stroke (UWO—patients not known to be asleep at time of onset but start of symptoms not known as language, attentional, or other cognitive deficits preclude patient reporting and no other witnesses present); and (3) witnessed onset stroke (WO—symptom onset time is witnessed and reported by patient or other observer).
Between 2014 and 2016, 6 positive randomized controlled trials established the superiority of endovascular thrombectomy over medical therapy alone in ischemic stroke patients with large vessel occlusions who were predominantly treated within 0 to 6 hours from time last seen well.1–5,11 Consequently, endovascular thrombectomy within 6 hours from time last seen well has been endorsed as class I evidence in guidelines published by multiple organizations. The subsequently published DAWN (Diffusion Weighted Imaging [DWI] or Computerized Tomography Perfusion [CTP] Assessment With Clinical Mismatch in the Triage of Wake Up and Late Presenting Strokes Undergoing Neurointervention) and DEFUSE 3 randomized trials have demonstrated benefit of thrombectomy over medical therapy in later-presenting patients with proximal large vessel occlusion and substantial mismatch between infarcted brain and at risk but still viable brain up to 24 hours from time last seen well, resulting in class I evidence endorsement of this approach.12,13 However, despite previous studies demonstrating that clinical outcomes after thrombectomy in patients with mismatch treated beyond 8 hours are not significantly different in patients presenting with wake-up stroke compared with those presenting with witnessed onset stroke,14 it has been suggested that the positive results of late onset trials may have been driven primarily by the high proportion of patients presenting with wake-up stroke.15 These patients would presumably experience the onset of stroke close to the time point of symptoms discovery and thus were de facto treated within the 6-hour time window, which is known to be associated with benefit from thrombectomy.
Therefore, lingering skepticism remains regarding the benefit of thrombectomy in patients with witnessed onset stroke presenting beyond 6 hours.15 To address the uncertainty about differences in treatment effect of thrombectomy in late presenting patients according to mode of onset, a prespecified analysis of the DAWN trial aimed to compare outcome rates across the 3 modes of onset (WUS, UWO, and WO). In addition to mode of onset, the time from when symptoms were first observed to randomization was prospectively recorded to clarify the proportion of patients with WUS or UWS who were randomized beyond 6 hours from the time they were found with neurological deficit (patients with confirmed onset beyond 6 hours from symptoms first observed).10 In patients with WO mode of onset, the time last seen well and the time symptoms were first observed are identical. In patients with WUS or UWS onset, the time last seen well are longer than the time symptoms were first observed.
Methods
Patient Selection and Randomization
Local institutional review board approval was granted at all participating centers, and informed consent was obtained for all enrolled patients. The data that support the findings of this study are available from the corresponding author on reasonable request. Details of the DAWN trial methodology and primary outcomes have been described previously.10 The DAWN trial was a global, multicenter, Bayesian adaptive-enrichment, PROBE trial (prospective, randomized, open, blinded end point) comparing thrombectomy with the Trevo device versus medical management. Enrollment occurred from September 2014 to February 2017. The planned sample size was a maximum of 500 patients. The first pre-specified analysis that allowed trial termination for efficacy reasons was performed when 200 patients crossed the prespecified success boundaries, leading to trial termination after enrollment of 206 patients. Trial inclusion was limited to patients 18 years of age or older with modified Rankin Scale (mRS) score of 0 or 1, presenting within 6 to 24 hours of time last seen well with an National Institutes of Health Stroke Scale (NIHSS) score of 10 or higher in the setting of a proximal anterior circulation large vessel occlusion involving the intra-cranial internal carotid artery or middle cerebral artery (M1 segment). A key inclusion criterion was the presence of mismatch between the severity of the clinical deficit as measured by the NIHSS and the baseline infarct volume measured using automated software (RAPID) based on the baseline computed tomography perfusion or DWI MRI (clinical infarct mismatch). Randomization occurred in a 1:1 ratio after stratification for clinical infarct mismatch, time last seen well (≤6–12 or 12–24 hours), and occlusion site (intracranial internal carotid artery or M1 segment).
Mode of Onset
The 3 distinct modes of onset: WUS, WO, and UWO as well as the time symptoms were first observed were prospectively recorded in each patient.
Patient Characteristics, Imaging Features, Treatment, and Outcome Metrics
Baseline patient characteristics as well as baseline imaging features were analyzed across groups. Of patients undergoing thrombectomy, procedural features were examined across groups. Clinical end points included the mRS analyzed via the utility-weighted method (UW-mRS)16 and in a dichotomized fashion by functional independence at 90 days (as defined by mRS score of 0–2). Safety end points included radiographic presence of hemorrhage as well as symptomatic intracranial hemorrhage (symptomatic intracerebral hemorrhage, as defined in the trial).8
Statistical Analysis
Descriptive statistics were compiled and presented separately for the WUS, WO, and UW cohorts. For categorical variables we used χ2 test and Fisher exact test, and for continuous variables the ANOVA test was used. We computed the absolute difference of clinical outcome rates between the treatment and control arms and associated CIs. For CIs, either normal approximation or Clopper-Pearson exact CIs were used. Univariate logistic regression was performed to evaluate the association between the treatment and 90-day good outcome, stratified by mode of onset. We then tested the heterogeneity of the treatment effects across the strata using the Breslow-Day test. All P are 2-sided and unadjusted for multiplicity. The analyses were carried out using SAS software version 9.4 (SAS Institute, Inc, Cary, NC).
Results
Baseline and Onset Characteristics
Of the 206 patients enrolled in the DAWN trial, a majority of patients presented as wake up strokes (55%; Table 1). Baseline characteristics across the 3 groups were notable for a trend toward more octogenarians in the WO and UWO patients compared with the WUS patients. Patients presenting with WUS and UWO strokes had higher baseline NIHSS score as compared with patients presenting with WO strokes. About 38% of patients were randomized beyond 6 hours of time symptoms were first observed, including WUS, UWOS, and WO.
| Wake Up (n=114) | Unwitnessed (n=67) | Witnessed (n=25) | P Value* | |
|---|---|---|---|---|
| Mean age | 68.7 (13.7) | 72.2 (12.9) | 70.4 (15.1) | 0.24 |
| Age over 80 | 18.4% | 38.8% | 28% | 0.01 |
| Hypertension | 76.3% | 81.8% | 70.8% | 0.49 |
| Dyslipidemia | 61.8% | 50.7% | 69.6% | 0.20 |
| Blood glucose | 121.8±68.3 | 121.8±58.4 | 103.7±66.3 | 0.87 |
| Baseline NIHSS | 17 (14–20) | 19 (15–24) | 14 (12–16) | <0.001 |
| Core infarct size | 12.4 (11.7) | 11.3 (10.9) | 8.2 (8.8) | 0.93 |
| ASPECTS | 7.4±1.5 | 7.4±1.6 | 7.3±1.5 | 0.97 |
| Time last seen well—median (h) | 13.3 (10.4–15.9) | 14.5 (9.8–17.8) | 8.3 (7.7–10.8) | <0.001 |
| Time symptoms were first observed—median (h) | 4.7 (3.4–6.4) | 4.8 (3.6–6.2) | 8.3 (7.7–10.8) | <0.001 |
| Transfers | 57.0% | 55.2% | 76.0% | 0.17 |
| Patients randomized to thrombectomy | 58.8% (67) | 43.3% (29) | 44.0% (11) | 0.09 |
ASPECTS indicates Alberta Stroke Program Early CT Score; and NIHSS, National Institutes of Health Stroke Scale.
Procedural Features of Patients Undergoing Thrombectomy
In patients undergoing endovascular therapy, there were no significant differences in the use of general anesthesia or other procedural aspects (mean number of passes, procedure duration, and recanalization rates). Door to qualifying image time was longer in patients who presented as UWO compared with WUS and WO patients (Table 2).
| Wake Up (n=67) | Unwitnessed (n=29) | Witnessed (n=11) | P Value | |
|---|---|---|---|---|
| Door to scan | 78.4 (47.5–101.7) | 100 (66.8–129.6) | 87.8 (56.2–119.0) | 0.03 |
| Randomization to arterial puncture (hours) | 16 (7–29) | 17 (10–25) | 16 (9–33) | 0.81 |
| General anesthesia | 12.1% | 6.9% | 9.1% | 0.91 |
| Mean no. of passes | 2.5 | 2.2 | 2.2 | 0.69 |
| Procedure time (minutes) | 56 (33–102) | 46 (31–82) | 59 (39–84) | 0.59 |
| eTICI ≥2b50 | 81.8% | 89.7% | 81.8% | 0.10 |
TICI indicates Thrombolysis in Cerebral Infarction.
Clinical Outcomes Across Mode of Onset
Patients undergoing thrombectomy had significantly higher rates of mRS score 0 to 2 at 90 days compared with patients treated with medical management alone. Rates of mRS score 0 to 2 were higher in patients undergoing thrombectomy irrespective of mode of onset (P for heterogeneity=0.786). The unadjusted treatment effect was nominally the highest for WO (OR: 95% CI, 8.15 [2.9–23.2]) followed by WUS (OR: 95% CI, 6.4 [1.1–37.7]) and then UWO (OR: 95% CI, 4.7 [1.4–15.4]; however, these differences were not statistically significant
Safety
When stratified by mode of presentation, the observed safety outcomes were overall similar between the thrombectomy arm and the medical management arm, with a few exceptions (Table 3). Among the WUS patients and UW patients, symptomatic intracerebral hemorrhage was more common among the thrombectomy arm (WUS: 3%, UW: 13.8%) than the medical management arm (WUS: 0%, UW: 7.9%). Among the UW patients, higher stroke related mortality and higher all-cause mortality were observed during the follow-up period in the medical management arm (26.3%), compared with the thrombectomy arm (stroke-related mortality: 17.2%, all-cause mortality: 20.7%).
| Thrombectomy | Control | Absolute Difference | P Value | |
|---|---|---|---|---|
| Functional independence by mode of onset | ||||
| Overall | 48.6% (52/107) | 13.1% (13/99) | 35.5% (23.2–46.2) | <0.001 |
| WUS | 49.3% (33/67) | 10.6% (5/47) | 38.7% (23.7–53.5) | <0.001 |
| WO | 63.6% (7/11) | 21.4% (3/14) | 42.2% (3.7–67.5) | 0.05 |
| UW | 41.4% (12/29) | 13.2% (5/38) | 28.2% (7.0–47.6) | 0.01 |
| sICH (ECASSIII)* | ||||
| WUS | 3.0% (2/67) | 0.0% (0/47) | 3.0% (−1.1% to 7.1%) | 0.51 |
| WO | 0.0% (0/11) | 0.0% (0/14) | 0.0% (0.0% to 0.0%) | 1 |
| UW | 13.8% (4/29) | 7.9% (3/38) | 5.9% (–9.3% to 21.1%) | 0.45 |
| Stroke-related mortality | ||||
| WUS | 16.4% (11/67) | 14.9% (7/47) | 1.5% (–13.1% to 14.5%) | 0.99 |
| WO | 9.1% (1/11) | 7.1% (1/14) | 1.9% (–19.7% to 23.6%) | 0.99 |
| UW | 17.2% (5/29) | 26.3% (10/38) | –9.1% (–27.5% to 11.6%) | 0.56 |
| All-cause mortality | ||||
| WUS | 19.4% (13/67) | 14.9% (7/47) | 4.5% (–9.4% to 18.4%) | 0.62 |
| WO | 9.1% (1/11) | 7.1% (1/14) | 1.9% (–19.7% to 23.6%) | 0.99 |
| UW | 20.7% (6/29) | 26.3% (10/38) | –5.6% (–26.0% to 14.7%) | 0.78 |
NIHSS indicates National Institutes of Health Stroke Scale; sICH, symptomatic intracranial hemorrhage; UWO, unwitnessed onset; WO, witnessed onset; and WUS, wake up stroke.
*
sICH; per a modified ECASS III definition8 (any apparently extravascular blood within the cranium that is associated with increase of ≥4 NIHSS points or that led to death and was judged to be the predominant cause of a neurologic deterioration), within 24 (−6/+24) hours post randomization adjudicated by the Clinical Events Committee.
Predictors of mRS Score 0 to 2
In multivariate analysis, independent predictors of mRS score 0 to 2 included thrombectomy, baseline NIHSS, history of diabetes mellitus, history of active tobacco use, and baseline infarct size. Mode of onset was not predictive of mRS score 0 to 2 (Figure).
Discussion
The main finding of this prespecified secondary analysis from the DAWN trial is that in patients with clinical imaging mismatch, benefit of thrombectomy is present with no significant differences in magnitude across the 3 distinct modes of onset: WUS, UWO, and WO. Nearly 40% of nonwake-up stroke patients were randomized >6 hours from time symptoms were first observed. In those patients, both clinical outcomes and treatment effect were no worse than those noted in WUS. Thus, our findings provide reassurance that, among late-presenting patients, when substantial clinical—core mismatch is present, UWO and WO patients benefit comparably to WUS patients from endovascular thrombectomy.
Of the 206 subjects enrolled in the DAWN trial, 55% were WUS, 33% were UWO strokes, and only 12% were WO strokes. Vascular risk factors were well matched for all groups by mode of onset. WU and UWO strokes had significantly higher NIHSS score and relatively higher ischemic core volume at onset compared with WO strokes. UWO strokes had a higher proportion of octogenarians. Despite these differences, a large treatment effect (absolute difference in rates of good outcome at 3 months, NNT, adjusted treatment effect) was observed in all the groups: WU (38.7%, 2.58–10), UWO (28.2%, 3.54–5.5), and WO (42.2%, 2.36–14.5). Furthermore, the treatment effect is not modified by mode of onset. Therefore, our study confirms that thrombectomy is highly effective and should be offered to all late-presenting strokes with LVO meeting DAWN trial criteria, regardless of mode of onset.
The overarching importance of pathophysiological information (presence of substantial areas of salvageable brain) as a predictor of treatment effect of thrombectomy over time and consequently mode of onset has significant patient care consequences as restriction of treatment to fixed time windows is fraught with significant disadvantages. Not only is the establishment of the stroke onset often times imprecise17 but also a significant proportion of patients with acute stroke because of LVO still arrive to the hospital beyond 6 hours resulting in the exclusion of a significant proportion of patients from treatment if selection is driven only based on time as a criteria.18 This problem is of particular importance for countries with less sophisticated systems of care (in which the majority of the earth’s population resides) where only a small fraction of the population arrives to the hospital within 6 hours.
Reassurance that patients stand to benefit from thrombectomy even if the stroke onset is witnessed to be up to 24 hours is important because it may increase treatment rates in these patients who currently may be excluded from treatment based on the witnessed onset of symptoms beyond 6 hours of time last seen well. Time may be used as a surrogate for physiology. The earlier patients present, the more likely they are to have a pathophysiological constellation favorable to reperfusion, which typically entails the presence of salvageable brain ascertained by subtracting the volume of infarct from the volume of critically hypoperfused brain. However, the presence of salvageable brain tissue in the setting of LVO is also a function of collateral blood supply. Clinically observed heterogeneity in infarct core size indicates that large variation in infarct growth rate exists, which is primarily driven by collaterals and leads to distinct patient populations recognized as fast versus slow progressors of infarct growth.19,20 Based on the presence of substantial mismatch beyond 6 hours from last seen well as a prerequisite for enrollment, the DAWN trial has included a patient population enriched with slow progressors.
Relatively lower NIHSS score and nominally better outcomes in witnessed strokes as compared with wake up and unwitnessed strokes is observed in our study. This observation confirms the findings of previous retrospective studies that this population of patients with witnessed onset stroke and mismatch criteria as defined in the DAWN trial is homogenous being almost exclusively composed of patients with slow rates of infarct growth.14 A certain proportion of patients in wake up and unwitnessed onset strokes will experience the onset of neurological deficit very close to the time they are actually found with deficit. Because a substantial proportion of patients with proximal LVO stroke and small baseline infarct presenting in the early time window have a higher infarct growth rate than those presenting beyond 6 hours, the patient population of wake up and unknown onset stroke is more heterogenous in terms of infarct progression compared with those with witnessed onset.21 A higher proportion of substantial infarct growth in the WUS and UOS compared with the WOS explains the numerically higher rate of mRS score 0 to 2 and 24-hour infarct volumes in the latter group of patients.
Limitations
Our study has its limitations. The small number of patients in witnessed and unwitnessed stroke onset subgroups limits the power for comparative analysis. The analyses on safety outcomes are based on sparse data and should be interpreted with caution. Conservative mismatch selection criteria for enrollment in the DAWN trial, similar to the DEFUSE 3 trial, have limited the generalizability of these 2 trials and may have excluded significant patient populations that also benefit from thrombectomy.22
Conclusions
All DAWN trial eligible patients could be considered for thrombectomy as clinical benefit and magnitude of treatment effect are not different across wake up, unwitnessed and witnessed modes of onset.
Acknowledgments
Drs Jadhav, Nogueira, and Jovin participated in conception and design and analysis and interpretation of data. All the authors participated in acquisition of data, critically revising the article, and providing administrative/technical/material support. Jadhav participated in drafting the article. Nogueira and Jovin participated in study supervision.
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© 2019 American Heart Association, Inc.
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History
Received: 10 April 2019
Revision received: 6 August 2019
Accepted: 14 August 2019
Published online: 1 October 2019
Published in print: November 2019
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Disclosures
Dr Jovin has the following disclosures: Consultant: Cerenovus (steering committee/DSMB-modest), Stryker Neurovascular (PI DAWN-unpaid [Diffusion Weighted Imaging (DWI) or Computerized Tomography Perfusion (CTP) Assessment With Clinical Mismatch in the Triage of Wake Up and Late Presenting Strokes Undergoing Neurointervention]). Stock: Anaconda, Silk Road, Blockade Medical, Route 92, Corindus, FreeOx Biotech, Viz.ai, Imperative Care. Dr Nogueira reports potential conflicts with Stryker Neurovascular (DAWN Trial Principal Investigator—no compensation, Trevo Retriever Registry Steering Committee—no compensation, TREVO-2 Trial Principal Investigator-modest; Consultant—modest), Medtronic (SWIFT Trial [SOLITAIRE FR With the Intention for Thrombectomy] Steering Committee—modest; SWIFT-Prime Trial Steering Committee—no compensation; significant STAR Trial Angiographic Core Lab), Penumbra (3D Separator Trial Executive Committee—no compensation), Cerenovus/Neuravi (ENDOLOW Trial Principal Investigator, EXCELLENT Registry Principal Investigator, ARISE-2 trial [Analysis of Revascularization in Ischemic Stroke With EmboTrap] Steering Committee—no compensation, Physician Advisory Board, modest), Phenox (Physician Advisory Board, modest), Anaconda (modest Physician Advisory Board), Genentech (modest Physician Advisory Board), Biogen (modest Physician Advisory Board), Prolong Pharmaceuticals (modest Physician Advisory Board), Allm, Inc (no compensation Physician Advisory Board), IschemaView (modest Speaker), Brainomix (no compensation Research Software Use), Sensome (no compensation Research Device Use), Viz-AI (Physician Advisory Board, stock options), Philips (no compensation Research Software Use, modest Speaker), and Corindus Vascular Robotics (Physician Advisory Board, stock options); Vesalio (PAB, stock options); Brazilian Ministry of Health (no compensation RESILIENT trial PI). Dr Haussen is a modest consultant for Stryker. Dr Bonafe is a consultant for Stryker, Medtronic, and Phenox. Dr Cognard reports personal fees from Cerenovus, and personal fees from MIVI outside the submitted work. Dr Yavagal is a consultant for Medtronic, Neural Analytics, Cerenovus, Rapid Medical (Steering Committee Member of TIGER Clinical Trial [Treatment With Intent to Generate Reperfusion] and Consultant); Stryker (funding for patient enrollment in DAWN trial as sponsor of the trial); Member of Technical Advisory Panel of Joint Commission Stroke Center Certification; Personal fees (InNeuroCo). Dr Hanel reports receiving consulting fees from Stryker, MicroVention, and Codman and grant support and consulting fees from Medtronic and holding stock in Neurvana, Three Rivers Medical, and InNeuroCo. Other from Phenox, Elum, Mivi, Cerebrotech. A.E. Hassan is a consultant, speaker, and proctor for Medtronic, Stryker, and Microvention and a consultant/speaker for Penumbra, Balt, and GE Heathcare. Personal fees and Other from Genentech outside the submitted work. Dr Ribo is a consultant for Cerenovus, Medtronic, Stryker, Apta Targets, Anaconda Biomed, and has equity ownership interest in Anaconda Biomed. Dr Cognard is a consultant for Stryker, Microvention, and Medtronic. A.E. Hassan is a consultant, speaker and proctor for Medtronic, Stryker, and Microvention; and a consultant/speaker for Penumbra, Balt and GE Heathcare. Y. Zhang is an employee of Stryker. Dr. Smith receives fees for serving as chair of a data and safety monitoring board from Stryker. Dr Saver is an employee of the University of California. The University of California has patent rights in retrieval devices for stroke. Dr. Saver has served as an unpaid site investigator in multicenter trials sponsored by Medtronic, Stryker, and Neuravia/Cerenovus for which the UC Regents received payments on the basis of clinical trial contracts for the number of subjects enrolled. Dr. Saver has received contracted hourly payments from Medtronic, Stryker, and Neuravia/Cerenovus and contracted stock options from Rapid Medical for services as a scientific consultant advising on rigorous trial design and conduct. Dr Liebeskind receives support as a consultant as imaging core lab for Stryker, Medtronic, Cerenovus, Vesalio, Neurvana, and Rapid Medical. The other authors report no conflicts.
Sources of Funding
The DAWN trial (Diffusion Weighted Imaging [DWI] or Computerized Tomography Perfusion [CTP] Assessment With Clinical Mismatch in the Triage of Wake Up and Late Presenting Strokes Undergoing Neurointervention) was funded by Stryker Neurovascular, Inc.
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- Endovascular thrombectomy after 24 hours for patients with acute ischemic stroke due to large vessel occlusion: A systematic review and meta-analysis of outcomes, Clinical Neurology and Neurosurgery, 247, (108610), (2024).https://doi.org/10.1016/j.clineuro.2024.108610
- Mode of Onset Modifies the Effect of Time to Endovascular Reperfusion on Clinical Outcomes after Acute Ischemic Stroke: An Analysis of the DAWN Trial , Annals of Neurology, 96, 2, (356-364), (2024).https://doi.org/10.1002/ana.26968
- Treatment with intravenous alteplase in ischaemic stroke patients with onset time between 4.5 and 24 hours (HOPE): protocol for a randomised, controlled, multicentre study, Stroke and Vascular Neurology, 9, 3, (318-323), (2023).https://doi.org/10.1136/svn-2022-002154
- Intraoperative neurophysiologic monitoring during aortic arch surgery, The Journal of Thoracic and Cardiovascular Surgery, 165, 6, (1971-1981.e2), (2023).https://doi.org/10.1016/j.jtcvs.2021.07.025
- Percutaneous management of acute ischaemic stroke, Heart, 109, 10, (794-800), (2023).https://doi.org/10.1136/heartjnl-2022-321604
- Mechanical Thrombectomy in the Late Presentation of Anterior Circulation Large Vessel Occlusion Stroke: A Guideline From the Society of Vascular and Interventional Neurology Guidelines and Practice Standards Committee, Stroke: Vascular and Interventional Neurology, 3, 1, (2022)./doi/10.1161/SVIN.122.000512
- Outcomes of wake-up stroke undergoing mechanical thrombectomy: A systematic review and meta-analysis, Interventional Neuroradiology, 30, 3, (412-418), (2022).https://doi.org/10.1177/15910199221133167
- Translating Animal Models of Ischemic Stroke to the Human Condition, Translational Stroke Research, 14, 6, (842-853), (2022).https://doi.org/10.1007/s12975-022-01082-9
- The Impact of Time to Reperfusion on Recanalization Rates and Outcome After Mechanical Thrombectomy, Annals of Indian Academy of Neurology, 25, 2, (256-260), (2022).https://doi.org/10.4103/aian.aian_909_21
- Thrombectomy for anterior circulation stroke beyond 6 h from time last known well (AURORA): a systematic review and individual patient data meta-analysis, The Lancet, 399, 10321, (249-258), (2022).https://doi.org/10.1016/S0140-6736(21)01341-6
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