Safety and Efficacy of Tenecteplase in Older Patients With Large Vessel Occlusion: A Pooled Analysis of the EXTEND-IA TNK Trials

Neurology ◽  
2022 ◽  
pp. 10.1212/WNL.0000000000013302
Author(s):  
Vignan Yogendrakumar ◽  
Leonid Churilov ◽  
Peter J Mitchell ◽  
Timothy J Kleinig ◽  
Nawaf Yassi ◽  
...  
Keyword(s):  
Treatment Effect ◽  
Symptom Onset ◽  
Pooled Analysis ◽  
Large Vessel ◽  
Large Vessel Occlusion ◽  
Vessel Occlusion ◽  
Safety And Efficacy ◽  
Logistic Regression Models ◽  
Link Type

Background and Objectives:Detailed study of tenecteplase (TNK) in patients greater than 80 years of age is limited. The objective of our study was to assess the safety and efficacy of TNK at 0.25 and 0.40 mg/kg doses in patients greater than 80 years with large vessel occlusion.Methods:A pooled analysis of the EXTEND-IA TNK randomized controlled trials (n=502). Patients were adults presenting with ischemic stroke due to occlusion of the intracranial internal carotid, middle cerebral, or basilar artery presenting within 4.5 hours of symptom onset. We compared the treatment effect of TNK 0.25mg/kg, TNK 0.40mg/kg, and alteplase 0.90mg/kg, stratifying for patient age (>80 years). Outcomes evaluated include 90-day modified Rankin scale (mRS), all-cause mortality, and symptomatic ICH. Treatment effect was adjusted for baseline NIHSS, age, and time from symptom onset to puncture via mixed effects proportional odds and logistic regression models.Results:In patients >80 years (n=137), TNK 0.25 mg/kg was associated with improved 90-day mRS (median 3 vs. 4, adjusted common OR=2.70, 95% CI: 1.23-5.94) and reduced mortality (aOR=0.34, 95% CI: 0.13-0.91) versus 0.40 mg/kg. TNK 0.25 mg/kg was associated with improved 90-day mRS (median 3 vs. 4, acOR=2.28, 95% CI: 1.03-5.05) versus alteplase. No difference in 90-day mRS or mortality was detected between alteplase and TNK 0.40 mg/kg. Symptomatic ICH was observed in 4 patients treated with TNK 0.40 mg/kg, one patient treated with alteplase and zero patients treated with TNK 0.25 mg/kg. In patients ≤ 80 years, no differences in 90-day mRS, mortality, or symptomatic ICH was observed between TNK 0.25 mg/kg, alteplase, and TNK 0.40 mg/kg.Conclusions:TNK 0.25 mg/kg was associated with improved 90-day mRS and lower mortality in patients greater than 80 years of age. No differences between the doses were observed in younger patients.Classification of Evidence:This study provides Class II evidence that tenecteplase 0.25 mg/kg given before endovascular therapy in patients >80 years old with large vessel occlusion stroke is associated with better functional outcomes at 90 days and reduced mortality when compared to tenecteplase 0.40 mg/kg or alteplase 0.90 mg/kg.Trial Registration:ClinicalTrials.gov Identifiers: NCT02388061, NCT03340493https://www.clinicaltrials.gov/ct2/show/NCT02388061https://www.clinicaltrials.gov/ct2/show/NCT03340493

Reader response: Comparative safety and efficacy of combined IVT and MT with direct MT in large vessel occlusion

Neurology ◽  
2018 ◽  
Vol 91 (24) ◽  
pp. 1114.2-1115
Author(s):  
Aravind Ganesh ◽  
Bijoy K. Menon ◽  
Mayank Goyal ◽  
Andrew M. Demchuk ◽  
Michael D. Hill
Keyword(s):  
Reader Response ◽  
Large Vessel ◽  
Large Vessel Occlusion ◽  
Vessel Occlusion ◽  
Safety And Efficacy ◽  
Comparative Safety

Antiplatelet pretreatment and outcomes following mechanical thrombectomy for emergent large vessel occlusion strokes

2017 ◽  
Vol 10 (9) ◽  
pp. 828-833 ◽  
Author(s):  
Abhi Pandhi ◽  
Georgios Tsivgoulis ◽  
Rashi Krishnan ◽  
Muhammad F Ishfaq ◽  
Savdeep Singh ◽  
...  
Keyword(s):  
Mechanical Thrombectomy ◽  
Intravenous Thrombolysis ◽  
Functional Independence ◽  
Large Vessel ◽  
Vessel Occlusion ◽  
Safety And Efficacy ◽  
Logistic Regression Models ◽  
Scale Scores ◽  
Stroke Center ◽  
Few Data

BackgroundFew data are available regarding the safety and efficacy of antiplatelet (APT) pretreatment in acute ischemic stroke (AIS) patients with emergent large vessel occlusions (ELVO) treated with mechanical thrombectomy (MT). We sought to evaluate the association of APT pretreatment with safety and efficacy outcomes following MT for ELVO.MethodsConsecutive ELVO patients treated with MT during a 4-year period in a tertiary stroke center were evaluated. The following outcomes were documented using standard definitions: symptomatic intracranial hemorrhage (sICH), successful recanalization (SR; modified TICI score 2b/3), mortality, and functional independence (modified Rankin Scale scores of 0–2).ResultsThe study population included 217 patients with ELVO (mean age 62±14 years, 50% men, median NIH Stroke Scale score 16). APT pretreatment was documented in 71 cases (33%). Patients with APT pretreatment had higher SR rates (77% vs 61%; P=0.013). The two groups did not differ in terms of sICH (6% vs 7%), 3-month mortality (25% vs 26%), and 3-month functional independence (50% vs 48%). Pretreatment with APT was independently associated with increased likelihood of SR (OR 2.18, 95% CI1.01 to 4.73; P=0.048) on multivariable logistic regression models adjusting for potential confounders. A significant interaction (P=0.014) of intravenous thrombolysis (IVT) pretreatment on the association of pre-hospital antiplatelet use with SR was detected. APT pretreatment was associated with SR (OR 2.74, 95% CI 1.15 to 6.54; P=0.024) in patients treated with combination therapy (IVT and MT) but not in those treated with direct MT (OR 1.78, 95% CI 0.63 to 5.03; P=0.276).ConclusionAPT pretreatment does not increase the risk of sICH and may independently improve the odds of SR in patients with ELVO treated with MT. The former association appears to be modified by IVT.

Author response: Comparative safety and efficacy of combined IVT and MT with direct MT in large vessel occlusion

Neurology ◽  
2018 ◽  
Vol 91 (24) ◽  
pp. 1116-1116
Author(s):  
Nitin Goyal ◽  
Georgios Tsivgoulis ◽  
Andrei V. Alexandrov ◽  
Adam S. Arthur
Keyword(s):  
Large Vessel ◽  
Author Response ◽  
Large Vessel Occlusion ◽  
Vessel Occlusion ◽  
Safety And Efficacy ◽  
Comparative Safety

Unexplained early neurological deterioration after endovascular treatment for acute large vessel occlusion: incidence, predictors, and clinical impact: Data from ANGEL-ACT registry

2021 ◽  
pp. neurintsurg-2021-017956
Author(s):  
Dapeng Sun ◽  
Xu Tong ◽  
Xiaochuan Huo ◽  
Baixue Jia ◽  
Raynald ◽  
...  
Keyword(s):  
Endovascular Treatment ◽  
Daily Practice ◽  
Clinical Impact ◽  
Neurological Deterioration ◽  
Large Vessel ◽  
Large Vessel Occlusion ◽  
Vessel Occlusion ◽  
Clinical Trial Registration ◽  
Link Type ◽  
Early Neurological Deterioration

BackgroundEarly neurological deterioration (END) may occur in some patients with acute large vessel occlusion (LVO) undergoing endovascular treatment (EVT). Despite several clear causes of END, such as symptomatic intracranial hemorrhage, failure of recanalization, and intraprocedure complications, a particular END, termed unexplained END (ENDunexplained), exists. We aimed to investigate the incidence, independent predictors, and clinical impact of ENDunexplained after EVT in patients with acute LVO.MethodsSubjects were selected from the ANGEL-ACT registry. ENDunexplained was defined as ≥4-point increase in the National Institutes of Health Stroke Scale (NIHSS) score between baseline and 24 hours after EVT, without the causes listed above. Logistic regression analyses were performed to determine the independent predictors of ENDunexplained, as well as the association between ENDunexplained and 90-day outcomes assessed by modified Rankin Scale (mRS) score.ResultsAmong the 1557 enrolled patients, the incidence of ENDunexplained was 4.3% (67/1557). Admission NIHSS ≤8 (OR=6.88, 95% CI 3.86 to 12.26, p<0.001), general anesthesia (OR=3.15, 95% CI 1.81 to 5.48, p<0.001), admission neutrophil to lymphocyte ratio >5 (OR=2.82, 95% CI 1.61 to 4.94, p<0.001), and number of EVT attempts >3 (OR=2.11, 95% CI 1.14 to 3.89, p=0.018) were associated independently with a high risk of ENDunexplained. Furthermore, patients with ENDunexplained were associated with a shift toward worse 90-day outcomes (mRS 5 vs 3, common OR=5.24, 95% CI 3.22 to 8.52, p<0.001).ConclusionsENDunexplained associated with poor 90day outcomes occurred in 4.3% of patients with acute LVO undergoing EVT. Several independent predictors of ENDunexplained were identified in this study, which should be considered in daily practice to improve acute LVO management.Clinical trial Registrationhttp://wwwclinicaltrialsgovNCT03370939.

Sonothrombolysis in Patients With Acute Ischemic Stroke With Large Vessel Occlusion: An Individual Patient Data Meta-Analysis

Stroke ◽  
2021 ◽  
Author(s):  
Georgios Tsivgoulis ◽  
Aristeidis H. Katsanos ◽  
Jürgen Eggers ◽  
Vincent Larrue ◽  
Lars Thomassen ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Individual Patient Data ◽  
Intravenous Thrombolysis ◽  
Large Vessel ◽  
Large Vessel Occlusion ◽  
Controlled Clinical Trials ◽  
Vessel Occlusion ◽  
Safety And Efficacy ◽  
Randomized Controlled Clinical Trials ◽  
Randomized Controlled

Background and Purpose: Evidence about the utility of ultrasound-enhanced thrombolysis (sonothrombolysis) in patients with acute ischemic stroke (AIS) is conflicting. We aimed to evaluate the safety and efficacy of sonothrombolysis in patients with AIS with large vessel occlusion, by analyzing individual patient data of available randomized-controlled clinical trials. Methods: We included all available randomized-controlled clinical trials comparing sonothrombolysis with or without addition of microspheres (treatment group) to intravenous thrombolysis alone (control group) in patients with AIS with large vessel occlusion. The primary outcome measure was the rate of complete recanalization at 1 to 36 hours following intravenous thrombolysis initiation. We present crude odds ratios (ORs) and ORs adjusted for the predefined variables of age, sex, baseline stroke severity, systolic blood pressure, and onset-to-treatment time. Results: We included 7 randomized controlled clinical trials that enrolled 1102 patients with AIS. A total of 138 and 134 confirmed large vessel occlusion patients were randomized to treatment and control groups respectively. Patients randomized to sonothrombolysis had increased odds of complete recanalization compared with patients receiving intravenous thrombolysis alone (40.3% versus 22.4%; OR, 2.17 [95% CI, 1.03–4.54]; adjusted OR, 2.33 [95% CI, 1.02–5.34]). The likelihood of symptomatic intracranial hemorrhage was not significantly different between the 2 groups (7.3% versus 3.7%; OR, 2.03 [95% CI, 0.68–6.11]; adjusted OR, 2.55 [95% CI, 0.76–8.52]). No differences in the likelihood of asymptomatic intracranial hemorrhage, 3-month favorable functional and 3-month functional independence were documented. Conclusions: Sonothrombolysis was associated with a nearly 2-fold increase in the odds of complete recanalization compared with intravenous thrombolysis alone in patients with AIS with large vessel occlusions. Further study of the safety and efficacy of sonothrombolysis is warranted.

Admission hyperglycemia and outcomes in large vessel occlusion strokes treated with mechanical thrombectomy

2017 ◽  
Vol 10 (2) ◽  
pp. 112-117 ◽  
Author(s):  
Nitin Goyal ◽  
Georgios Tsivgoulis ◽  
Abhi Pandhi ◽  
Kira Dillard ◽  
Aristeidis H Katsanos ◽  
...  
Keyword(s):  
Mechanical Thrombectomy ◽  
Functional Independence ◽  
Serum Glucose ◽  
Adverse Outcomes ◽  
Large Vessel ◽  
Functional Improvement ◽  
Large Vessel Occlusion ◽  
Vessel Occlusion ◽  
Logistic Regression Models ◽  
Median Admission

Background and purposeHigher admission serum glucose levels have been associated with poor outcomes in patients with acute ischemic stroke (AIS) treated with IV thrombolysis. We sought to evaluate the association of admission serum glucose with early outcomes of patients with emergent large vessel occlusion (ELVO) treated with mechanical thrombectomy (MT).MethodsConsecutive AIS patients due to ELVO treated with MT in three tertiary stroke centers were evaluated. The following outcomes were documented using standard definitions: symptomatic intracranial hemorrhage (sICH), complete reperfusion, mortality, functional independence (modified Rankin Scale (mRS) score of 0–2), and functional improvement (shift in mRS score) at 3 months. The association of admission serum glucose and admission hyperglycemia (>140 mg/dL) with outcomes was evaluated using univariable and multivariable binary and ordinal logistic regression models.Results231 AIS patients with ELVO (mean age 62±14 years, 51% men, median admission National Institute of Health Stroke Scale score 16 points (IQR 12–21), median admission serum glucose 125 mg/dL (IQR 104–162)) were treated with MT. Admission hyperglycemia was associated with a lower likelihood of functional improvement (common OR 0.53; 95% CI 0.31 to 0.97; p=0.027) and higher odds of 3 month mortality (OR 2.76; 95% CI 1.40 to 5.44; p=0.004) in multivariable analyses adjusting for potential confounders. A 10 mg/dL increase in admission blood glucose was associated with a higher likelihood of sICH (OR 1.07; 95% CI 1.01 to 1.13; p=0.033) and 3 month mortality (OR 1.07; 95% CI 1.02 to 1.12; p=0.004) in multivariable models. There was no association between admission serum glucose or hyperglycemia and complete reperfusion.ConclusionsHigher admission serum glucose and admission hyperglycemia are independent predictors of adverse outcomes in ELVO patients treated with MT.

Abstract WP13: Stroke Severity and Revascularization are the Strongest Predictors of Outcome in Large Vessel Occlusion Strokes: Post-Hoc Analysis of the TREVO 2 Trial

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Helmi L Lutsep ◽  
Raul G Nogueira ◽  
Rishi Gupta ◽  
Tudor G Jovin ◽  
Gregory W Albers ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Left Hemisphere ◽  
Symptom Onset ◽  
Univariate Analysis ◽  
Large Vessel ◽  
P Value ◽  
Stroke Severity ◽  
Large Vessel Occlusion ◽  
Vessel Occlusion ◽  
Good Outcome

Introduction.: The Trevo Retriever showed higher recanalization rates and better outcomes than the Merci Retriever in patients with ischemic stroke due to large vessel occlusion (LVO) in TREVO 2. Hypothesis.: We assessed the hypothesis that except for device-related variables, predictors of good outcome would be similar in TREVO 2 and single arm Merci Retriever studies. Methods.: The study evaluated predictors of good outcome, modified Rankin Scale (mRS) 0-2 at 90 days, in TREVO 2 including those with ischemic stroke due to LVO aged 18-85 years with a National Institutes of Health Stroke Scale Score (NIHSS) 8-29 and a first device treatment pass within 8 hours of symptom onset. A secondary analysis investigated mortality predictors. Variables included baseline characteristics of age, sex, NIHSS, IV tPA use, occlusion side, most proximal occlusion site, stroke etiology, body mass index, systolic blood pressure (BP), diastolic BP, glucose; history including hypertension, diabetes, dyslipidemia, smoking, congestive heart failure (CHF), atrial fibrillation, previous coronary or cerebral ischemia; and procedural characteristics of time from symptom onset to arterial puncture, time to TICI ≥2 or end of procedure, device allocation, intubation status, rescue therapy usage and post device revascularization success TICI ≥ 2 per core lab. Variables were assessed with univariate analysis for association with mRS 0-2 and mortality and those with a p-value of <0.15 were eligible for the multivariate model. Results.: TREVO 2 data were available for 168 patients. Variables significant on multivariate analysis for an association with good outcome were baseline NIHSS (OR 0.76, 95% CI 0.67, 0.86), post device revascularization success per core lab (OR 117.6, 95% CI 8.40, 1645), diabetes (OR 0.12, 95% CI 0.03, 0.41), intubation (OR 0.11, 95% CI 0.03, 0.41) and left hemisphere involvement (OR 5.11, 95% CI 1.77, 14.71). Predictors of mortality included baseline NIHSS and left hemisphere involvement but also age and CHF. Conclusions.: While age did not appear as a predictor of good outcome and diabetes was negatively associated with it for the first time in a Merci analysis, predictors of favorable outcome in TREVO 2 were similar to those previously reported for the Merci Retriever.

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