scholarly journals Noninferiority Margins in Trials of Thrombectomy Devices for Acute Ischemic Stroke

Stroke ◽  
2019 ◽  
Vol 50 (12) ◽  
pp. 3519-3526 ◽  
Author(s):  
Chun-Jen Lin ◽  
Jeffrey L. Saver
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Primary Outcome ◽  
Coronary Revascularization ◽  
Functional Independence ◽  
Expert Survey ◽  
Cardiac Devices ◽  
Noninferiority Trials ◽  
First And Second Generation ◽  
Noninferiority Margin

Background and Purpose— Novel endovascular thrombectomy (EVT) devices for acute ischemic stroke are often cleared by regulatory agencies on the basis of noninferiority trials. The relation between the noninferiority margins used in trials and the minimal clinically important differences (MCIDs) determined by experts have not been systematically investigated. Methods— Systematic searches were performed to identify (1) all noninferiority design or noninferiority-presented stroke-EVT trials for acute ischemic stroke, (2) all studies determining the MCIDs for the same outcomes, and (3) all noninferiority coronary revascularization trials. Stroke-EVT trial results were reanalyzed using the broad noninferiority margins originally used and narrower noninferiority margins derived from formal MCID studies. Results— We identified 7 noninferiority-designed or noninferiority-interpreted stroke-EVT controlled trials, enrolling 1766 patients, variously comparing coil retrievers, first- and second-generation stent retrievers, and aspiration devices. In 6 trials, the primary outcome was achievement of reperfusion, using noninferiority margins of 15% (3 trials), 10% (2 trials), and 8% (1 trial). In contrast, a stroke expert survey identified the MCID for reperfusion as 3.1% to 5%, and cardiac trials used noninferiority margins of 3.5% to 4.4%. In one stroke-EVT trial, the primary outcome was functional independence, using a noninferiority margin of 15%. However, 2 stroke expert survey studies identified MCIDs for functional independence as having lower values, 5% and 1% to 1.5%. For both reperfusion and functional independence outcomes, all 7 trials demonstrated noninferiority with the broadest noninferiority margin, but only 4 and 3 trials demonstrated noninferiority with actual expert-derived margins for reperfusion and functional independence, respectively. Conclusions— Noninferiority margins used in EVT device trials have regularly exceeded the MCIDs determined by stroke experts, as well as margins used for cardiac devices. New approaches, such as the use of reasonably adequate performance margins, rather than noninferiority margins, are needed to optimize stroke-EVT trial design integrity and trial performance feasibility.

Association of admission leukocyte count with clinical outcomes in acute ischemic stroke patients undergoing intravenous thrombolysis with recombinant tissue plasminogen activator

2020 ◽  
Vol 17 ◽  
Author(s):  
Jie Chen ◽  
Fu-Liang Zhang ◽  
Shan Lv ◽  
Hang Jin ◽  
Yun Luo ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Leukocyte Count ◽  
Intravenous Thrombolysis ◽  
Recombinant Tissue Plasminogen Activator ◽  
Functional Independence ◽  
Tissue Plasminogen ◽  
Poor Outcomes

Objective:: Increased leukocyte count are positively associated with poor outcomes and all-cause mortality in coronary heart disease, cancer, and ischemic stroke. The role of leukocyte count in acute ischemic stroke (AIS) remains important. We aimed to investigate the association between admission leukocyte count before thrombolysis with recombinant tissue plasminogen activator (rt-PA) and 3-month outcomes in AIS patients. Methods:: This retrospective study included consecutive AIS patients who received intravenous (IV) rt-PA within 4.5 h of symptom onset between January 2016 and December 2018. We assessed outcomes including short-term hemorrhagic transformation (HT), 3-month mortality, and functional independence (modified Rankin Scale [mRS] score of 0–2 or 0–1). Results:: Among 579 patients who received IV rt-PA, 77 (13.3%) exhibited HT at 24 h, 43 (7.4%) died within 3 months, and 211 (36.4%) exhibited functional independence (mRS score: 0–2). Multivariable logistic regression revealed admission leukocyte count as an independent predictor of good and excellent outcomes at 3 months. Each 1-point increase in admission leukocyte count increased the odds of poor outcomes at 3 months by 7.6% (mRS score: 3–6, odds ratio (OR): 1.076, 95% confidence interval (CI): 1.003–1.154, p=0.041) and 7.8% (mRS score: 2–6, OR: 1.078, 95% CI: 1.006–1.154, p=0.033). Multivariable regression analysis revealed no association between HT and 3-month mortality. Admission neutrophil and lymphocyte count were not associated with 3-month functional outcomes or 3-month mortality. Conclusion:: Lower admission leukocyte count independently predicts good and excellent outcomes at 3 months in AIS patients undergoing rt-PA treatment.

Safety of early anticoagulation in patients treated with urgent reperfusion for acute ischemic stroke related to non-valvular atrial fibrillation

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Giustozzi
Keyword(s):  
Atrial Fibrillation ◽  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Major Bleeding ◽  
Oral Anticoagulation ◽  
Primary Outcome ◽  
Oral Anticoagulants ◽  
Early Recurrence ◽  
Optimal Timing ◽  
Hemorrhagic Event

Abstract Background The optimal timing for starting anticoagulation after an acute ischemic stroke related to non-valvular atrial fibrillation (AF) remains a challenge, especially in patients treated with systemic thrombolysis or mechanical thrombectomy. Purpose We aimed to assess the rates of early recurrence and major bleeding in patients with acute ischemic stroke and AF treated with thrombolytic therapy and/or thrombectomy who received oral anticoagulants for secondary prevention. Methods We combined the dataset of the RAF and the RAF-NOACs studies, which were prospective observational studies carried out from January 2012 to March 2014 and April 2014 to June 2016, respectively. We included consecutive patients with acute ischemic stroke and AF treated with either vitamin K antagonists (VKAs) or new oral anticoagulants (NOACs). Primary outcome was the composite of stroke, transient ischemic attack, symptomatic systemic embolism, symptomatic cerebral bleeding, and major extracerebral bleeding within 90 days from the inclusion. Results A total of 2,159 patients were included in the RAF and RAF-NOACs trials, of which 564 patients (26%) were treated with urgent reperfusion therapy. After acute stroke, 505 (90%) patients treated with reperfusion and 1,287 out of the 1,595 (81%) patients not treated with reperfusion started oral anticoagulation. Timing of starting oral anticoagulation was similar in reperfusion-treated and untreated patients (13.5±23.3 vs 12.3±18.3 days, respectively, p=0.287). At 90 days, the composite rate of recurrence and major bleeding occurred in 37 (7%) of patients treated with reperfusion treatment and in 139 (9%) of untreated patients (p=0.127). Twenty-four (4%) reperfusion-treated patients and 82 (5%) untreated patients had early recurrence while major bleeding occurred in 13 (2%) treated and in 64 (4%) untreated patients, respectively. Seven patients in the untreated group experienced both an ischemic and hemorrhagic event. Figure 1 shows the risk of early recurrence and major bleeding over time in patients treated and not treated with reperfusion treatments. The use of NOACs was associated with a favorable rate of the primary outcome compared to VKAs (Odd ratio 0.4, 95% Confidence Interval 0.3–0.7). Conclusions Reperfusion treatment did not influence the risk of early recurrence and major bleeding in patients with AF-related acute ischemic stroke who started anticoagulant treatment. Figure 1 Funding Acknowledgement Type of funding source: None

scholarly journals Recanalisation theraphy for acute ischemic stroke in cancer patients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Giovanni Merlino ◽  
Carmelo Smeralda ◽  
Gian Luigi Gigli ◽  
Simone Lorenzut ◽  
Sara Pez ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Metastatic Cancer ◽  
Intravenous Thrombolysis ◽  
Functional Independence ◽  
University Hospital ◽  
Bridging Therapy ◽  
Patients With Cancer ◽  
Increased Risk ◽  
Active Cancer

AbstractTo date, very few studies focused their attention on efficacy and safety of recanalisation therapy in acute ischemic stroke (AIS) patients with cancer, reporting conflicting results. We retrospectively analysed data from our database of consecutive patients admitted to the Udine University Hospital with AIS that were treated with recanalisation therapy, i.e. intravenous thrombolysis (IVT), mechanical thrombectomy (MT), and bridging therapy, from January 2015 to December 2019. We compared 3-month dependency, 3-month mortality, and symptomatic intracranial haemorrhage (SICH) occurrence of patients with active cancer (AC) and remote cancer (RC) with that of patients without cancer (WC) undergoing recanalisation therapy for AIS. Patients were followed up for 3 months. Among the 613 AIS patients included in the study, 79 patients (12.9%) had either AC (n = 46; 7.5%) or RC (n = 33; 5.4%). Although AC patients, when treated with IVT, had a significantly increased risk of 3-month mortality [odds ratio (OR) 6.97, 95% confidence interval (CI) 2.42–20.07, p = 0.001] than WC patients, stroke-related deaths did not differ between AC and WC patients (30% vs. 28.8%, p = 0.939). There were no significant differences between AC and WC patients, when treated with MT ± IVT, regarding 3-month dependency, 3-month mortality and SICH. Functional independence, mortality, and SICH were similar between RC and WC patients. In conclusion, recanalisation therapy might be used in AIS patients with nonmetastatic AC and with RC. Further studies are needed to explore the outcome of AIS patients with metastatic cancer undergoing recanalisation therapy.

Non-contrast head CT alone for thrombectomy in acute ischemic stroke: analysis of the ANGEL-ACT registry

2021 ◽  
pp. neurintsurg-2021-017940
Author(s):  
Zeguang Ren ◽  
Gaoting Ma ◽  
Maxim Mokin ◽  
Ashutosh P Jadhav ◽  
Baixue Jia ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Clinical Outcomes ◽  
Primary Outcome ◽  
Ct Perfusion ◽  
Non Invasive ◽  
Vessel Imaging ◽  
Baseline Characteristics ◽  
Procedural Outcomes ◽  
Head Computed Tomography

BackgroudThe goal of this study was to determine if the choice of imaging paradigm performed in the emergency department influences the procedural or clinical outcomes after mechanical thrombectomy (MT).MethodsThis is a retrospective comparative outcome study which was conducted from the ANGEL-ACT registry. Comparisons were made between baseline characteristics and clinical outcomes of patients with acute ischemic stroke undergoing MT with non-contrast head computed tomography (NCHCT) alone versus patients undergoing NCHCT plus non-invasive vessel imaging (NVI) (including CT angiography (with or without CT perfusion) and magnetic resonance angiography). The primary outcome was the modified Rankin Scale (mRS) score at 90 days. Secondary outcomes included change in mRS score from baseline to 90 days, the proportions of mRS 0–1, 0–2, and 0–3, and dramatic clinical improvement at 24 hours. The safety outcomes were any intracranial hemorrhage (ICH), symptomatic ICH, and mortality within 90 days.ResultsA total of 894 patients met the inclusion criteria; 476 (53%) underwent NCHCT alone and 418 (47%) underwent NCHCT + NVI. In the NCHCT alone group, the door-to-reperfusion time was shorter by 47 min compared with the NCHCT + NVI group (219 vs 266 min, P<0.001). Patients in the NCHCT alone group showed a smaller increase in baseline mRS score at 90 days (median 3 vs 2 points; P=0.004) after adjustment. There were no significant differences between groups in the remaining clinical outcomes.ConclusionsIn patients selected for MT using NCHCT alone versus NCHCT + NVI, there were improved procedural outcomes and smaller increases in baseline mRS scores at 90 days.

Abstract T P48: Intravenous Thrombolysis Using Low-Dose Alteplase for Nonagenarians with Acute Ischemic Stroke: The SAMURAI rtPA Registry

Stroke ◽  
2014 ◽  
Vol 45 (suppl_1) ◽  
Author(s):  
Mikito Hayakawa ◽  
Masatoshi Koga ◽  
Shoichiro Sato ◽  
Shoji Arihiro ◽  
Yoshiaki Shiokawa ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Low Dose ◽  
Intravenous Thrombolysis ◽  
Functional Independence ◽  
Efficacy And Safety ◽  
Multivariate Adjustment ◽  
Potential Efficacy ◽  
Symptomatic Intracranial Hemorrhage ◽  
Baseline Characteristics

Objective: Although intravenous thrombolysis (IVT) using alteplase for octogenarians with acute ischemic stroke becomes relatively familiar, it is unclear whether IVT for nonagenarians is a futile intervention. The purpose of this study is to clarify the efficacy and safety of IVT using low-dose alteplase (0.6 mg/kg) for nonagenarians compared with octogenarians. Methods: Stroke Acute Management with Urgent Risk-factor Assessment and Improvement (SAMURAI) rtPA registry retrospectively collected 600 consecutive acute stroke patients receiving IVT from 10 Japanese stroke centers between October 2005 and July 2008. We extracted all octogenarians (O group) and nonagenarians (N group) from the registry. We compared baseline characteristics, symptomatic intracranial hemorrhage (SICH), and 3-month outcomes between the groups. 3-month outcomes include; functional independence (FI) defined as a mRS score 0-2, good outcome (GO) as a mRS score 0-2 or same as the premorbid mRS, poor outcome (PO) defined as a mRS score 5-6, and death. Results: Twenty-five nonagenarians (mean age, 93 years) and 124 octogenarians (mean age, 84 years) were included. N group was more female-predominant (76% versus 56%, p=0.06) and premorbidly dependent (44% versus 14%, p<0.001) than O group. There were no significant differences of median baseline NIHSS score (16 versus 14, p=0.95) and Alberta Stroke Program Early CT Score (9 versus 9, p=0.36) between the groups. The rate of FI tended to be lower in N group than O group (16% versus 36%, p=0.06), otherwise, the differences of the rates of GO (28% versus 37%, p=0.39), PO (40% versus 36%, p=0.73), death (20% versus 11%, p=0.23) and SICH (0% versus 2.4%, p=1.00) were not significant between the groups. In comparison with O group, N group was not associated with 3-month clinical outcomes (FI; OR 0.61; 95% CI, 0.15-2.42, GO; 0.98; 0.31-3.07, PO; 0.63; 0.15-2.70, death; 3.18; 0.62-16.3) and SICH (0.68; 0.17-2.69) after multivariate adjustment. Conclusions: IVT using low-dose alteplase for N group resulted in less frequent achievement of FI mainly because of more premorbid dependency than O group, however, showed at least a similar safety and a potential efficacy.

scholarly journals Mechanical thrombectomy in acute ischemic stroke with tandem occlusions: impact of extracranial carotid lesion etiology on endovascular management and outcome

2021 ◽  
Vol 51 (1) ◽  
pp. E6
Author(s):  
Valerio Da Ros ◽  
Jacopo Scaggiante ◽  
Francesca Pitocchi ◽  
Fabrizio Sallustio ◽  
Simona Lattanzi ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Clinical Outcome ◽  
Acute Ischemic Stroke ◽  
Demographic Data ◽  
Functional Independence ◽  
Artery Occlusion ◽  
Endovascular Management ◽  
Retrograde Approach ◽  
Antegrade Approach ◽  
Tandem Occlusion

OBJECTIVE Different etiologies of extracranial internal carotid artery steno-occlusive lesions (ECLs) in patients with acute ischemic stroke (AIS) and tandem occlusion (TO) have been pooled together in randomized trials. However, carotid atherosclerosis (CA) and carotid dissection (CD), the two most common ECL etiologies, are distinct nosological entities. The authors aimed to determine if ECL etiology has impacts on the endovascular management and outcome of patients with TO. METHODS A multicenter, retrospective study of prospectively collected data was conducted. AIS patients were included who had TO due to internal CA or CD and ipsilateral M1 middle cerebral artery occlusion and underwent endovascular treatment (EVT). Comparative analyses including demographic data, safety, successful recanalization rates, and clinical outcome were performed according to EVT and ECL etiology. RESULTS In total, 214 AIS patients with TOs were included (77.6% CA related, 22.4% CD related). Patients treated with a retrograde approach were more often functionally independent at 3 months than patients treated with an antegrade approach (OR 0.6, 95% CI 0.4–0.9). Patients with CD-related TOs achieved 90-day clinical independence more often than patients with CA-related TOs (OR 1.4, 95% CI 1.1–2.0). Emergency stenting use was associated with good 3-month clinical outcome only in patients with CA-related TOs (OR 1.4, 95% CI 1.1–2.1). Symptomatic intracranial hemorrhage (sICH) occurred in 10.7% of patients, without differences associated with ECL etiology. CONCLUSIONS ECL etiology impacts both EVT approach and clinical outcome in patients with TOs. Patients with CD-related TO achieved higher 3-month functional independence rates than patients with CA-related TOs. A retrograde approach can be desirable for both CA- and CD-related TOs, and emergency stenting is likely better justified in CA-related TOs.

scholarly journals Clinical profile of patients with acute ischemic stroke receiving intravenous thrombolysis (rtPA-alteplase)

2018 ◽  
Vol 5 (1) ◽  
pp. 164
Author(s):  
Shiva Prasad Jagini ◽  
Suresh I.
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Prospective Observational Study ◽  
Primary Outcome ◽  
Intravenous Thrombolysis ◽  
Clinical Profile ◽  
Favorable Outcome ◽  
Nihss Score ◽  
The Mean ◽  
Centre Hospital

Background: Stroke patients are at highest risk death in the first few weeks after the event, and between 20-50% die within first month depending on type, severity, age, co-morbidities and effectiveness of treatment of complications. Objective of this study was to clinical profile of patients with acute ischemic stroke receiving intravenous thrombolysis (rtPA-alteplase).Methods: Prospective Observational study of 26 cases of acute ischemic stroke receiving IV thrombolysis using rtPA-alteplase at Kovai Medical Centre Hospital, Coimbatore over a period of 1 year 9 months.Results: 21 cases had NIHSS score of range 10 to 22. The mean NIHSS score at admission is 13.5. 15 subjects (57.7%) had achieved primary outcome in this study. MRS Score of 0 to 2 is considered as favorable outcome. In this study 20 subjects (76.92 %) had favorable outcome at the end of 3 months.Conclusions: Majority of the patients receiving rtPA-alteplase had favorable outcome.

Abstract TMP48: Effect of Pre-Morbid Antianxiety and Antidepressant Medications on Ischemic Stroke Functional Outcome

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Cecilia Peterson ◽  
Ka-Ho Wong ◽  
Michael Dela Cruz ◽  
Kirby Taylor ◽  
Jennifer J Majersik ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Regression Models ◽  
Primary Outcome ◽  
Negative Impact ◽  
Secondary Analysis ◽  
Anxiety And Depression ◽  
Neuroprotective Effects ◽  
Logistic Regression Models ◽  
Antidepressant Medications

Introduction: Antianxiety and antidepressant medications have shown some neuroprotective effects following stroke. However, the effect of premorbid use of these medications remains unclear. Hypothesis: Pre-morbid exposure to antianxiety or antidepressant medications will negatively impact recovery from acute ischemic stroke, measured by modified Rankin scale (mRS) at 90 days after stroke onset. Methods: This is a secondary analysis of the Albumin in Acute Ischemic Stroke (ALIAS) 2 trial. The primary outcome is 90-day mRS 0-1. The exposure is premorbid antidepressant or antianxiety medication. We fit univariate and multivariate logistic regression models to our outcome, with covariates chosen using a stepwise backwards interactive selection. Results: We included 806 patients with a mean (SD) age of 64.4 (12.8) years. The median (IQR) NIH Stroke Scale was 11 (8, 17) and 54.3% were male, 75.6% were Caucasian, 88.8% received tPA, 72.5% had hypertension, and 20.3% had diabetes. A total of 140/806 (17.4%) of patients took either an antidepressant or antianxiety medication, of which 91 took an antidepressant, 34 took an antianxiety medication, and 15 took both. The median (IQR) mRS Scale was one point higher in patients on antidepressant or antianxiety medication pre-stroke (3 vs. 2, p=0.019). The primary outcome of mRS 0-1 was seen in 37.7% of all patients. Taking an antidepressant or antianxiety medication was associated with lower odds of a good outcome in univariate (OR 0.61, 95% CI 0.41-0.91, p=0.015) and multivariate models (aOR 0.62, 95% CI 0.40-0.95, p=0.027) (Table 1). Conclusion: Pre-morbid exposure to antianxiety or antidepressant medications is associated with a worse outcome after acute ischemic stroke. This may be due to a negative impact of pre-stroke anxiety and depression that outweigh any neuroprotective factors of these medications.

EXPRESS: Impact of renal impairment on short-term outcomes following endovascular thrombectomy for acute ischemic stroke: A systematic review and meta-analysis

2021 ◽  
pp. 174749302110473
Author(s):  
Jin Pyeong Jeon ◽  
Chih-Hao Chen ◽  
Fon-Yih Tsuang ◽  
Jianming Liu ◽  
Michael D Hill ◽  
...  
Keyword(s):  
Systematic Review ◽  
Ischemic Stroke ◽  
Renal Impairment ◽  
Acute Ischemic Stroke ◽  
Meta Analysis ◽  
Functional Independence ◽  
Continuous Variable ◽  
Endovascular Thrombectomy ◽  
Symptomatic Intracerebral Hemorrhage ◽  
The Impact

Background. The impact of renal impairment (RI) on the outcomes of patients with acute ischemic stroke (AIS) treated with endovascular thrombectomy (EVT) was relatively limited and contradictory. We performed a systematic review and meta-analysis to investigate this. Aims. We registered a protocol on September 2020 and searched MEDLINE, EMBASE, and Google Scholar accordingly. RI was defined as an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2. Predefined outcomes included functional independence (defined as a modified Rankin Scale of 0, 1, or 2) at 3 months, successful reperfusion, mortality, and symptomatic intracerebral hemorrhage (sICH). Summary of review. Eleven studies involving 3453 patients were included. For the unadjusted outcomes, RI was associated with fewer functional independence (odds ratio (OR), 0.49; 95% confidence interval (CI), 0.39–0.62) and higher mortality (OR, 2.55; 95% CI, 2.03–3.21). RI was not associated with successful reperfusion (OR, 0.80; 95% CI 0.63–1.00) and sICH (OR, 1.41; 95% CI, 0.95–2.10). For the adjusted outcomes, results derived from a multivariate meta-analysis were consistent with the respective unadjusted outcomes: functional independence (OR, 0.59; 95% CI, 0.45–0.77), mortality (OR, 2.23, 95% CI, 1.45–3.43), and sICH (OR, 1.34; 95% CI, 0.85–2.10). Conclusions. We presented the first systematic review to demonstrate that RI is associated with fewer functional independence and higher mortality. Future EVT studies should publish complete renal eGFR data to facilitate prognostic studies and permit eGFR to be analyzed in a continuous variable. Systematic Review Registration: PROSPERO CRD42020191309

Sign in / Sign up

Export Citation Format

Share Document