scholarly journals Tenecteplase Thrombolysis for Acute Ischemic Stroke

Stroke ◽  
2020 ◽  
Vol 51 (11) ◽  
pp. 3440-3451
Author(s):  
Steven J. Warach ◽  
Adrienne N. Dula ◽  
Truman J. Milling
Keyword(s):  
Ischemic Stroke ◽  
Intracranial Hemorrhage ◽  
Time Window ◽  
Large Vessel ◽  
Bolus Administration ◽  
Phase 2 ◽  
Qualitative Synthesis ◽  
Phase 3 ◽  
Symptomatic Intracranial Hemorrhage ◽  
Meta Analyses

Tenecteplase is a fibrinolytic drug with higher fibrin specificity and longer half-life than the standard stroke thrombolytic, alteplase, permitting the convenience of single bolus administration. Tenecteplase, at 0.5 mg/kg, has regulatory approval to treat ST-segment–elevation myocardial infarction, for which it has equivalent 30-day mortality and fewer systemic hemorrhages. Investigated as a thrombolytic for ischemic stroke over the past 15 years, tenecteplase is currently being studied in several phase 3 trials. Based on a systematic literature search, we provide a qualitative synthesis of published stroke clinical trials of tenecteplase that (1) performed randomized comparisons with alteplase, (2) compared different doses of tenecteplase, or (3) provided unique quantitative meta-analyses. Four phase 2 and one phase 3 study performed randomized comparisons with alteplase. These and other phase 2 studies compared different tenecteplase doses and effects on early outcomes of recanalization, reperfusion, and substantial neurological improvement, as well as symptomatic intracranial hemorrhage and 3-month disability on the modified Rankin Scale. Although no single trial prospectively demonstrated superiority or noninferiority of tenecteplase on clinical outcome, meta-analyses of these trials (1585 patients randomized) point to tenecteplase superiority in recanalization of large vessel occlusions and noninferiority in disability-free 3-month outcome, without increases in symptomatic intracranial hemorrhage or mortality. Doses of 0.25 and 0.4 mg/kg have been tested, but no advantage of the higher dose has been suggested by the results. Current clinical practice guidelines for stroke include intravenous tenecteplase at either dose as a second-tier option, with the 0.25 mg/kg dose recommended for large vessel occlusions, based on a phase 2 trial that demonstrated superior recanalization and improved 3-month outcome relative to alteplase. Ongoing randomized phase 3 trials may better define the comparative risks and benefits of tenecteplase and alteplase for stroke thrombolysis and answer questions of tenecteplase efficacy in the >4.5-hour time window, in wake-up stroke, and in combination with endovascular thrombectomy.

Prevalence of large vessel occlusion in patients presenting with acute ischemic stroke: a 10-year systematic review of the literature

2018 ◽  
Vol 11 (3) ◽  
pp. 241-245 ◽  
Author(s):  
Nikita Lakomkin ◽  
Mandip Dhamoon ◽  
Kirsten Carroll ◽  
Inder Paul Singh ◽  
Stanley Tuhrim ◽  
...  
Keyword(s):  
Systematic Review ◽  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Large Vessel ◽  
Large Vessel Occlusion ◽  
Review Of The Literature ◽  
Qualitative Synthesis ◽  
Vessel Occlusion ◽  
Number Of Patients ◽  
Meta Analyses

BackgroundAccurate assessment of the prevalence of large vessel occlusion (LVO) in patients presenting with acute ischemic stroke (AIS) is critical for optimal resource allocation in neurovascular intervention.ObjectiveTo perform a systematic review of the literature in order to identify the proportion of patients with AIS presenting with LVO on image analysis.MethodsA systematic review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines in order to identify studies reporting LVO rates for patients presenting with AIS. Studies that included patients younger than 18 years, were non-clinical, or did not report LVO rates in the context of a consecutive AIS series were excluded. Characteristics regarding presentation, diagnosis, and LVO classification were recorded for each paper.ResultsSixteen studies, spanning a total of 11 763 patients assessed for stroke, were included in the qualitative synthesis. The majority (10/16) of articles reported LVO rates exceeding 30% in patients presenting with AIS. There was substantial variability in the LVO definitions used, with nine unique classification schemes among the 16 studies. The mean prevalence of LVO was 31.1% across all studies, and 29.3% when weighted by the number of patients included in each study.ConclusionsDespite the wide variability in LVO classification, the majority of studies in the last 10 years report a high prevalence of LVO in patients presenting with AIS. These rates of LVO may have implications for the volume of patients with AIS who may benefit from endovascular therapy.

scholarly journals Intra-Arterial Adjunctive Medications for Acute Ischemic Stroke During Mechanical Thrombectomy

Stroke ◽  
2021 ◽  
Vol 52 (4) ◽  
pp. 1192-1202
Author(s):  
Vanessa H.E. Chen ◽  
Grace K.H. Lee ◽  
Choon-Han Tan ◽  
Aloysius S.T. Leow ◽  
Ying-Kiat Tan ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Intracranial Hemorrhage ◽  
Risk Ratio ◽  
Mechanical Thrombectomy ◽  
Large Vessel ◽  
Tissue Type ◽  
Large Vessel Occlusion ◽  
Vessel Occlusion ◽  
Symptomatic Intracranial Hemorrhage

Background and Purpose: In patients with acute ischemic stroke with large vessel occlusion, the role of intra-arterial adjunctive medications (IAMs), such as urokinase, tPA (tissue-type plasminogen activator), or glycoprotein IIb/IIIa inhibitors, during mechanical thrombectomy (MT) has not been clearly established. We aim to evaluate the efficacy and safety of concomitant or rescue IAM for acute ischemic stroke with large vessel occlusion patients undergoing MT. Methods: We searched Medline, Embase, and Cochrane Stroke Group Trials Register databases from inception until March 13, 2020. We analyzed all studies with patients diagnosed with acute ischemic stroke with large vessel occlusion in the anterior or posterior circulation that provided data for the two treatment arms, (1) MT+IAM and (2) MT only, and also reported on at least one of the following efficacy outcomes, recanalization and 90-day modified Rankin Scale, or safety outcomes, symptomatic intracranial hemorrhage and 90-day mortality. Data were collated in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Results: Sixteen nonrandomized observational studies with a total of 4581 patients were analyzed. MT only was performed in 3233 (70.6%) patients, while 1348 (29.4%) patients were treated with both MT and IAM. As compared with patients treated with MT alone, patients treated with combination therapy (MT+IAM) had a higher likelihood of achieving good functional outcome (risk ratio, 1.13 [95% CI, 1.03–1.24]) and a lower risk of 90-day mortality (risk ratio, 0.82 [95% CI, 0.72–0.94]). There was no significant difference in successful recanalization (risk ratio, 1.02 [95% CI, 0.99–1.06]) and symptomatic intracranial hemorrhage between the two groups (risk ratio, 1.13 [95% CI, 0.87–1.46]). Conclusions: In acute ischemic stroke with large vessel occlusion, the use of IAM together with MT may achieve better functional outcomes and lower mortality rates. Randomized controlled trials are warranted to establish the safety and efficacy of IAM as adjunctive treatment to MT.

Endovascular versus medical therapy for large-vessel anterior occlusive stroke presenting with mild symptoms

2019 ◽  
Vol 15 (3) ◽  
pp. 324-331 ◽  
Author(s):  
Dylan N Wolman ◽  
David G Marcellus ◽  
Maarten G Lansberg ◽  
Gregory Albers ◽  
Adrien Guenego ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Intracranial Hemorrhage ◽  
Medical Management ◽  
Large Vessel ◽  
Large Vessel Occlusion ◽  
Stroke Patients ◽  
Vessel Occlusion ◽  
Endovascular Thrombectomy ◽  
Symptomatic Intracranial Hemorrhage

Background Acute ischemic stroke patients with a large-vessel occlusion but mild symptoms (NIHSS ≤ 6) pose a treatment dilemma between medical management and endovascular thrombectomy. Aims To evaluate the differences in clinical outcomes of endovascular thrombectomy-eligible patients with target-mismatch perfusion profiles who undergo either medical management or endovascular thrombectomy. Methods Forty-seven patients with acute ischemic stroke due to large-vessel occlusion, NIHSS ≤ 6, and a target-mismatch perfusion imaging profile were included. Patients underwent medical management or endovascular thrombectomy following treating neurointerventionalist and neurologist consensus. The primary outcome measure was NIHSS shift. Secondary outcome measures were symptomatic intracranial hemorrhage, in-hospital mortality, and 90-day mRS scores. The primary intention-to-treat and as-treated analyses were compared to determine the impact of crossover patient allocation on study outcome measures. Results Forty-seven patients were included. Thirty underwent medical management (64%) and 17 underwent endovascular thrombectomy (36%). Three medical management patients underwent endovascular thrombectomy due to early clinical deterioration. Presentation NIHSS ( P = 0.82), NIHSS shift ( P = 0.62), and 90-day functional independence (mRS 0–2; P = 0.25) were similar between groups. Endovascular thrombectomy patients demonstrated an increased overall rate of intracranial hemorrhage (35.3% vs. 10.0%; P = 0.04), but symptomatic intracranial hemorrhage was similar between groups ( P = 0.25). In-hospital mortality was similar between groups ( P = 0.46), though all two deaths in the medical management group occurred among crossover patients. Endovascular thrombectomy patients demonstrated a longer length of stay (7.6 ± 7.2 vs. 4.3 ± 3.9 days; P = 0.04) and a higher frequency of unfavorable discharge to a skilled-nursing facility ( P = 0.03) rather than home ( P = 0.05). Conclusions Endovascular thrombectomy may pose an unfavorable risk-benefit profile over medical management for endovascular thrombectomy-eligible acute ischemic stroke patients with mild symptoms, which warrants a randomized trial in this subpopulation.

Nomogram to Predict Symptomatic Intracranial Hemorrhage after Intravenous Thrombolysis in Acute Ischemic Stroke in an Asian Population.

2021 ◽  
Vol 19 ◽  
Author(s):  
Xiaohua Xie ◽  
Jie Yang ◽  
Lijie Ren ◽  
Shiyu Hu ◽  
Wancheng Lian ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Intracranial Hemorrhage ◽  
Calibration Curve ◽  
Intravenous Thrombolysis ◽  
Asian Population ◽  
Individual Risk ◽  
Clinical Effects ◽  
Symptomatic Intracranial Hemorrhage

Background: Symptomatic intracranial hemorrhage (sICH) is a serious hemorrhagic complication after intravenous thrombolysis (IVT) in acute ischemic stroke (AIS) patients. Most existing predictive scoring systems were derived from Western countries Objective: To develop a nomogram to predict the possibility of sICH after IVT in an Asian population. Methods: This retrospective cohort study included AIS patients treated with recombinant tissue plasminogen activator (rt-PA) in a tertiary hospital in Shenzhen, China, from January 2014 to December 2020. The end point was sICH within 36 hours of IVT treatment. Multivariable logistic regression was used to identify risk factors of sICH, and a predictive nomogram was developed. Area under the curve of receiver operating characteristic curves (AUC), calibration curve, and decision curve analyses were performed. The nomogram was validated by bootstrap resampling Results: Data on a total of 462 patients were collected, of whom 20 patients (4.3%) developed sICH. In the multivariate logistic regression model, the National Institute of Health stroke scale scores (NIHSS) (odds ratio [OR], 1.14; 95% confidence interval [CI], 1.06–1.23, P < 0.001), onset to treatment time (OTT) (OR, 1.02; 95% CI, 1.01–1.03, P < 0.001), neutrophil to lymphocyte ratio (NLR) (OR, 1.22; 95% CI, 1.09–1.35, P < 0.001), and cardioembolism (OR, 3.74; 95% CI, 1.23–11.39, P = 0.020) were independent predictors for sICH and were used to construct a nomogram. Our nomogram exhibited favorable discrimination ability [AUC, 0.878; specificity, 87.35%; and sensitivity, 73.81%]. Bootstrapping for 500 repetitions was performed to further validate the nomogram. The AUC of the bootstrap model was 0.877 (95% CI: 0.823–0.922). The calibration curve exhibited good fit and calibration. The decision curve revealed good positive net benefits and clinical effects Conclusion: The nomogram consisted of the predictors NIHSS, OTT, NLR, and cardioembolism could be used as an auxiliary tool to predict the individual risk of sICH in Chinese AIS patients after IVT. Further external verification among more diverse patient populations is needed to demonstrate the accuracy of the model’s predictions.

Abstract 3183: Prognosis of Mild Ischemic Stroke with Large Vessel Occlusion

Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
Esteban Cheng-Ching ◽  
Russell Cerejo ◽  
Ken Uchino ◽  
Muhammad S Hussain ◽  
Gabor Toth
Keyword(s):  
Ischemic Stroke ◽  
Endovascular Therapy ◽  
Time Window ◽  
Optimal Treatment ◽  
Large Vessel ◽  
Stroke Severity ◽  
Large Vessel Occlusion ◽  
Vessel Occlusion ◽  
Nihss Score ◽  
Mild Stroke

Background and purpose Large vessel occlusion (LVO) in acute ischemic stroke has been reported to be an independent predictor of unfavorable clinical outcome. However, the prognosis and optimal treatment of patients with only mild neurologic deficits due to LVO are not known. Methods We performed a retrospective chart review from a database of stroke patients admitted to our large academic medical center between July 1, 2010 and June 30 , 2011. Inclusion criteria were acute stroke or TIA, presentation within 9 hours from symptom onset, large vessel occlusion as a culprit of ischemic symptoms, and mild stroke severity with initial NIH Stroke Scale (NIHSS) score <8. Results We identified 59 patients with mild ischemic stroke or TIA, who were evaluated within 9 hours from onset. Of these, 13 (22%) had culprit large vessel occlusions. Five were female, 1 had diabetes, 12 had hypertension, 7 had hyperlipidemia, 2 had atrial fibrillation and 7 were smokers. The median NIHSS score was 5. The location of arterial occlusions were 5 in M1 segment of the middle cerebral artery (MCA), 6 in M2 segment of MCA, 1 each in posterior cerebral and vertebral arteries. Two patients received acute therapy, 1 with intravenous thrombolysis and 1 with endovascular therapy. Reasons for withholding thrombolytic therapy were time window in 8, mild stroke severity in 2, and atypical presentations in 2. Reasons for withholding acute endovascular therapy were mild stroke severity in 7, imaging finding in 2, technical considerations in 2, and lack of consent in 1. From hospital admission to discharge, 10 (77%) patients had symptom improvement, 2 had worsening, and one was unchanged. At 30 days, 5 (38%) had good outcome with a modified Rankin Scale (mRS) of 0-1. Three (23%) had mRS of 2, one (8%) patient had mRS of 3. Outcomes for 4 patients were unknown. Conclusions A significant proportion of patients presenting with mild ischemic symptoms has large vessel occlusion. Acute treatment in this population is frequently withheld due to mild severity or thrombolytic time window. Despite mild symptoms at presentation, some patients are left with moderate disability. Optimal treatment options for this population should be further evaluated in a larger group of patients.

Blood Pressure After Endovascular Thrombectomy and Outcomes in Patients With Acute Ischemic Stroke: An Individual Patient Data Meta-analysis

Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000013049
Author(s):  
Aristeidis H Katsanos ◽  
Konark Malhotra ◽  
Niaz Ahmed ◽  
Georgios Seitidis ◽  
Eva A. Mistry ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Intracranial Hemorrhage ◽  
Individual Patient Data ◽  
Patient Data ◽  
Neurological Deterioration ◽  
Endovascular Thrombectomy ◽  
Early Neurological Deterioration ◽  
Symptomatic Intracranial Hemorrhage

Objective:To explore the association between blood pressure (BP) levels after endovascular thrombectomy (EVT) and the clinical outcomes of acute ischemic stroke (AIS) patients with large vessel occlusion (LVO).Methods:A study was eligible if it enrolled AIS patients older than 18 years, with an LVO treated with either successful or unsuccessful EVT, and provided either individual or mean 24-hour systolic BP values after the end of the EVT procedure. Individual patient data from all studies were analyzed using a generalized linear mixed-effects model.Results:A total of 5874 patients (mean age: 69±14 years, 50% women, median NIHSS on admission: 16) from 7 published studies were included. Increasing mean systolic BP levels per 10 mm Hg during the first 24 hours after the end of the EVT were associated with a lower odds of functional improvement (unadjusted common OR=0.82, 95%CI:0.80-0.85; adjusted common OR=0.88, 95%CI:0.84-0.93) and modified Ranking Scale score≤2 (unadjusted OR=0.82, 95%CI:0.79-0.85; adjusted OR=0.87, 95%CI:0.82-0.93), and a higher odds of all-cause mortality (unadjusted OR=1.18, 95%CI:1.13-1.24; adjusted OR=1.15, 95%CI:1.06-1.23) at 3 months. Higher 24-hour mean systolic BP levels were also associated with an increased likelihood of early neurological deterioration (unadjusted OR=1.14, 95%CI:1.07-1.21; adjusted OR=1.14, 95%CI:1.03-1.24) and a higher odds of symptomatic intracranial hemorrhage (unadjusted OR=1.20, 95%CI:1.09-1.29; adjusted OR=1.20, 95%CI:1.03-1.38) after EVT.Conclusion:Increased mean systolic BP levels in the first 24 hours after EVT are independently associated with a higher odds of symptomatic intracranial hemorrhage, early neurological deterioration, three-month mortality, and worse three-month functional outcomes.

Abstract W MP6: SAVER I: Superselective Administration of VErapamil during Recanalization in Acute Ischemic Stroke. A Phase I Feasibility Study

Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Justin F Fraser ◽  
Michael E Maniskas ◽  
Abdulnasser Alhajeri ◽  
Gregory J Bix
Keyword(s):  
Ischemic Stroke ◽  
Phase I ◽  
Large Vessel ◽  
Direct Result ◽  
Dose Selection ◽  
Grading Scale ◽  
Symptomatic Intracranial Hemorrhage ◽  
Drug Studies ◽  
Acute Stroke Therapy ◽  
Large Vessel Stroke

Large vessel occlusive ischemic stroke results in high rates of morbidity and mortality. While intravenous t-PA and intra-arterial (IA) thrombectomy are mainstays in acute stroke therapy, clinical outcomes lag significantly behind improving rates of acute revascularization. Thus, there is a critical need for a novel adjunctive therapy to reduce stroke burden and to improve outcome. Previous neuroprotective drug studies failed due to long intervals between symptom onset and drug administration, lack of concordant thrombolytic revascularization, and lack of targeted administration to the affected vessel. Through a retro-engineered mouse model of large vessel stroke allowing concomitant recanalization and selective intra-arterial (IA) administration we previously evaluated verapamil, a calcium channel blocker (CCB) that is already safely injected intra-arterially (IA) for vasospasm. In this clinically relevant model, verapamil was highly neuroprotective when combined with vessel recanalization. Based on this data, we conducted a single-institution Phase I study to evaluate the feasibility and safety of superselective IA verapamil (10mg) administration immediately following mechanical thrombectomy. We collected information about demographics, location of the occlusion, last known normal time, time to and recanalization. Evaluation of CTA collateralization was performed using a previously a published grading scale (Souza et al. AJNR. 2012). The primary endpoint was symptomatic intracranial hemorrhage (ICH) within 24 hours post-procedure as defined by the Interventional Management Stroke (IMS) III Trial (Broderick et al. NEJM. 2013). Patients were monitored and graded at 3 months with the modified Rankin Score (mRS). Of the enrolled patients, none had a significant ICH, and none died as a direct result of the procedure. Clinical outcome results for patients were encouraging, and warrant further study. These results will be used to support a Phase II dose selection study.

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