scholarly journals Switching to Tenecteplase for Stroke Thrombolysis: Real-World Experience and Outcomes in a Regional Stroke Network

Stroke ◽  
2021 ◽  
Author(s):  
Karim Mahawish ◽  
John Gommans ◽  
Timothy Kleinig ◽  
Bhavesh Lallu ◽  
Alicia Tyson ◽  
...  

Background and Purpose: Due to practical advantages, increasing trial safety data, recent Australian Guideline endorsement and local population needs we switched to tenecteplase for stroke thrombolysis from alteplase. We describe our change process and real-world outcome data. Methods: Mixed-methods including stakeholder engagement, preimplementation and postimplementation surveys, and assessment of patient treatment rates, metrics, and clinical outcomes preimplementation and postimplementation adjusting regression analyses for age, sex, National Institutes of Health Stroke Scale, premorbid modified Rankin Scale score, and thrombectomy using New Zealand National Stroke Registry data. Results: Preswitch consultation involved stroke and emergency clinicians, pharmacists, national regulatory bodies, and hospital legal teams. All survey responders (90% response rate) supported the proposed change and remained satisfied 12 months postimplementation. Between January 2018 and February 2021, we treated 555 patients with alteplase and 283 with tenecteplase. Patients treated with tenecteplase had greater odds of a favorable modified Rankin Scale using both shift (adjusted odds ratio, 1.60 [95% CI, 1.15–2.22]) and dichotomous analyses (modified Rankin Scale score, 0–2; adjusted odds ratio, 2.17 [95% CI, 1.31–3.59]) and shorter median (interquartile range) door-to-needle time (median, 53 [38–73.5] versus 61 minutes [45–85], P =0.0002). Symptomatic intracranial hemorrhage rates (tenecteplase 1.8% versus 3.4%; adjusted odds ratio, 0.46 [95% CI, 0.13–1.64]), death by day 7 (tenecteplase 7.5% versus 11.8%; adjusted odds ratio, 0.46 [95% CI, 0.21–0.99]), and median (interquartile range) needle to groin time for the 42 transferred regional patients (tenecteplase 155 [113–248] versus 200 [158–266]; P =0.27) did not significantly differ. Conclusions: Following stakeholder endorsement, a region-wide switch from alteplase to tenecteplase was successfully implemented. We found evidence of benefit and no evidence of harm.

Neurology ◽  
2017 ◽  
Vol 89 (15) ◽  
pp. 1561-1568 ◽  
Author(s):  
Niaz Ahmed ◽  
Kennedy R. Lees ◽  
Peter A. Ringleb ◽  
Christopher Bladin ◽  
David Collas ◽  
...  

Objective:To determine outcomes and risks of IV thrombolysis (IVT) in patients with acute ischemic stroke (AIS) >80 years of age within 3 hours compared to >3 to 4.5 hours recorded in the Safe Implementation of Treatment in Stroke (SITS) International Stroke Thrombolysis Registry.Methods:A total of 14,240 (year 2003–2015) patients >80 years of age with AIS were treated with IVT ≤4.5 hours of stroke onset (3,558 in >3–4.5 hours). Of these, 8,658 (2,157 in >3–4.5 hours) were treated otherwise according to the European Summary of Product Characteristics (EU SmPC) criteria for alteplase. Outcomes were 3-month functional independence (modified Rankin Scale score 0–2), mortality, and symptomatic intracerebral hemorrhage (SICH)/SITS. Results were compared between the groups treated in >3 to 4.5 and ≤3 hours.Results:Median age was 84 years; 61% were female in both groups. Median NIH Stroke Scale score was 12 vs 14 in the >3- to 4.5- and ≤3-hour group, respectively. Three-month functional independence was 34% vs 35% (adjusted odds ratio [aOR] 0.78, 95% confidence interval [CI] 0.69–0.89, p < 0.001); mortality was 31% vs 32% (aOR 1.10, 95% CI 0.97–1.25, p = 0.13); and SICH/SITS was 2.7% vs 1.6% (aOR 1.72, 95% CI 1.25–2.35, p = 0.001). In EU SmPC–compliant patients, 3-month functional independence was 36 vs 37% (aOR 0.79, 95% CI 0.68–0.92, p = 0.002), mortality was 29% vs 29.6% (aOR 1.10, 95% CI 0.95–1.28, p = 0.20), and SICH/SITS was 2.7% vs 1.6% (aOR 1.62, 95% CI 1.12–2.34, p = 0.01).Conclusions:In this observational study, unselected patients >80 years of age treated with IVT after 3 hours vs earlier had a slightly higher rate of SICH and similar unadjusted functional outcome but poorer adjusted outcome. The absolute difference between the treatment groups is small, and elderly patients should not be denied IVT in the later time window solely because of age without other contraindications.


Stroke ◽  
2021 ◽  
Author(s):  
Tomas Dobrocky ◽  
Eike I. Piechowiak ◽  
Bastian Volbers ◽  
Nedelina Slavova ◽  
Johannes Kaesmacher ◽  
...  

Background and Purpose: Treatment in stroke patients with M2 segment occlusion of the middle cerebral artery presenting with mild neurological deficits is a matter of debate. The main purpose was to compare the outcome in patients with a minor stroke and a M2 occlusion. Methods: Consecutive intravenous thrombolysis (IVT) eligible patients admitted to the Bernese stroke center between January 2005 and January 2020 with acute occlusion of the M2 segment and National Institutes of Health Stroke Scale score ≤5 were included. Outcome was compared between IVT only versus endovascular therapy (EVT) including intra-arterial thrombolysis and mechanical thrombectomy (MT; ±IVT) and between IVT only versus MT only. Results: Among 169 patients (38.5% women, median age 70.2 years), 84 (49.7%) received IVT only and 85 (50.3%) EVT (±IVT), the latter including 39 (45.9%) treated with MT only. Groups were similar in sex, age, vascular risk factors, event cause, or preevent independency. Compared with IVT only, there was no difference in favorable outcome (modified Rankin Scale score, 0−2) for EVT (adjusted odds ratio, 0.96; adjusted P =0.935) or for MT only (adjusted odds ratio, 1.12; adjusted P =0.547) groups. Considering only patients treated after 2015, there was a significantly better 3-month modified Rankin Scale shift (adjusted P =0.032) in the EVT compared with the IVT only group. Conclusions: Our study demonstrates similar effectiveness of IVT only versus EVT (±IVT), and of IVT only versus MT only in patients with peripheral middle cerebral artery occlusions and minor neurological deficits and indicates a possible benefit of EVT considering only patients treated after 2015. There is an unmet need for randomized controlled trials in this stroke field, including imaging parameters, and more sophisticated evaluation of National Institutes of Health Stroke Scale score subitems, neurocognition, and quality of life neglected by the standard outcome scales such as modified Rankin Scale and National Institutes of Health Stroke Scale score.


Stroke ◽  
2020 ◽  
Vol 51 (9) ◽  
pp. 2817-2824
Author(s):  
Johanna M. Ospel ◽  
Petra Cimflova ◽  
Martha Marko ◽  
Arnuv Mayank ◽  
Moiz Hafeez ◽  
...  

Background and Purpose: The prognosis of medium vessel occlusions (MeVOs), that is, M2/3 middle cerebral artery, A2/3 anterior cerebral artery, and P2/3 posterior cerebral artery occlusions, is generally better compared with large vessel occlusions, since brain ischemia is less extensive. However, in some MeVO patients, infarcts are seen outside the territory of the occluded vessel (MeVO with discrepant infarcts). This study aims to determine the prevalence and clinical impact of discrepant infarct patterns in acute ischemic stroke due to MeVO. Methods: We pooled data of MeVO patients from INTERRSeCT (Identifying New Approaches to Optimize Thrombus Characterization for Predicting Early Recanalization and Reperfusion With IV Alteplase and Other Treatments Using Serial CT Angiography) and PRove-IT (Precise and Rapid Assessment of Collaterals Using Multi-Phase CTA in the Triage of Patients With Acute Ischemic Stroke for IA Therapy)—2 prospective cohort studies of patients with acute ischemic stroke. The combination of occlusion location on baseline computed tomography angiography and infarct location on follow-up computed tomography/magnetic resonance imaging was used to identify MeVOs with discrepant infarct patterns. Two definitions for discrepant infarcts were applied; one was more restrictive and purely based on infarct patterns of the basal ganglia, whereas the second one took cortical infarct patterns into account. Clinical outcomes of patients with versus without discrepant infarcts were summarized using descriptive statistics. Logistic regression was performed to obtain adjusted effect size estimates for the association of discrepant infarcts and good outcome, defined as a modified Rankin Scale score of 0 to 2, and excellent outcome (modified Rankin Scale score 0–1). Results: Two hundred sixty-two patients with MeVO were included in the analysis. The prevalence of discrepant infarcts was 39.7% (definition 1) and 21.0% (definition 2). Patients with discrepant infarcts were less likely to achieve good outcome (definition 1: adjusted odds ratio, 0.48 [95% CI, 0.25–0.91]; definition 2: adjusted odds ratio, 0.47 [95% CI, 0.22–0.99]). When definition 1 was applied, patients with discrepant infarcts were also less likely to achieve excellent outcome (definition 1: adjusted odds ratio, 0.55 [95% CI, 0.31–0.99]; definition 2: adjusted odds ratio, 0.62 [95% CI, 0.31–1.25]). Conclusions: MeVO patients with discrepant infarcts are common, and they are associated with more severe deficits and poor outcomes.


Stroke ◽  
2021 ◽  
Author(s):  
Mahmoud H. Mohammaden ◽  
Diogo C. Haussen ◽  
Leonardo Pisani ◽  
Alhamza R. Al-Bayati ◽  
Nicolas Bianchi ◽  
...  

Background and Purpose: There is a robust relationship between the duration of ischemia and functional outcomes after mechanical thrombectomy. Higher number of mechanical thrombectomy passes strongly correlate with lower chances of favorable outcomes. Indeed, previous studies have suggested that after multiple passes the procedure may be futile. However, using uncontrolled thresholds to define thrombectomy futility might be misleading. We aim to compare the outcome of successful reperfusion after 4 to 5 passes and ≥6 passes with those of failed reperfusion. Methods: A prospectively acquired mechanical thrombectomy database from January 2012 to October 2019 was reviewed. Patients were included if they had intracranial internal carotid artery or middle cerebral artery-M1/M2 occlusions and either achieved successful reperfusion after ≥4 passes or failed reperfusion. Reperfused patients (mTICI2b-3) were divided into 2 subgroups; (1) 4 to 5 passes and (2) ≥6 passes. Each subgroup was compared with a matched group of mechanical thrombectomy failure (mTICI0-2a). The primary outcome was the shift in the degree of disability at 90-day as measured by the modified Rankin Scale. Results: A total of 273 patients were included. As compared with matched failed reperfusion patients (n=62), those reperfused after 4 to 5 passes (n=62) had a favorable shift in the overall modified Rankin Scale score distribution (adjusted odds ratio, 3.992 [95% CI, 1.807–8.512], P =0.001] and higher rates of functional independence (31% versus 8.9%, P =0.004, adjusted odds ratio; 9.860 [95% CI, 2.323–41.845], P =0.002) at 90 days. Similarly, when compared with a matched group of failed reperfusion (n=42), patients reperfused after ≥6 passes (n=42) demonstrated a favorable shift in the overall modified Rankin Scale score distribution (adjusted odds ratio, 2.640 [95% CI, 1.073–6.686], P =0.037) and had higher rates of functional independence (36.8% vs 11.1%, P =0.004, adjusted odds ratio, 5.392 [95% CI, 1.185–24.530], P =0.029) at 90 day. Rates of parenchymal hematoma type-2 and 90-day mortality were comparable in the reperfused and nonreperfused groups. Conclusions: Achieving reperfusion despite multiple passes leads to improved outcomes compared with failed procedures. Arbitrary uncontrolled thresholds for a maximum number of passes to predict futile recanalization may lead to inappropriate early termination of procedures.


Stroke ◽  
2021 ◽  
Author(s):  
Chenchen Wei ◽  
Jeffrey Wang ◽  
Lydia D. Foster ◽  
Sharon D. Yeatts ◽  
Claudia Moy ◽  
...  

Background and Purpose: Hematoma volume (HV) is a powerful determinant of outcome after intracerebral hemorrhage. We examined whether the effect of the iron chelator, deferoxamine, on functional outcome varied depending on HV in the i-DEF trial (Intracerebral Hemorrhage Deferoxamine). Methods: A post hoc analysis of the i-DEF trial; participants were classified according to baseline HV (small <10 mL, moderate 10–30 mL, and large >30 mL). Favorable outcome was defined as a modified Rankin Scale score of 0–2 at day-180; secondarily at day-90. Logistic regression was used to evaluate the differential treatment effect according to HV. Results: Two hundred ninety-one subjects were included in the as-treated analysis; 121 with small, 114 moderate, and 56 large HV. Day-180 modified Rankin Scale scores were available for 270/291 subjects (111 with small, 105 moderate, and 54 large HV). There was a differential effect of treatment according to HV on day-180 outcomes ( P -for-interaction =0.0077); 50% (27/54) of deferoxamine-treated patients with moderate HV had favorable outcome compared with 25.5% (13/51) of placebo-treated subjects (adjusted odds ratio, 2.7 [95% CI, 1.13–6.27]; P =0.0258). Treatment effect was not significant for small (adjusted odds ratio, 1.37 [95% CI, 0.62–3.02]) or large (adjusted odds ratio, 0.12 [95% CI, 0.01–1.05]) HV. Results for day-90 outcomes were comparable ( P -for-interaction =0.0617). Sensitivity analyses yielded similar results. Conclusions: Among patients with moderate HV, a greater proportion of deferoxamine- than placebo-treated patients achieved modified Rankin Scale score 0–2. The treatment effect was not significant for small or large HVs. These findings have important trial design and therapeutic implications. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02175225.


Neurosurgery ◽  
2011 ◽  
Vol 70 (1) ◽  
pp. 155-161 ◽  
Author(s):  
Laurent Thines ◽  
Amir R. Dehdashti ◽  
Leodante da Costa ◽  
Michael Tymianski ◽  
Karel G. ter Brugge ◽  
...  

Abstract BACKGROUND Brainstem arteriovenous malformations are challenging lesions, and benefits of treatment are uncertain. OBJECTIVE To study the clinical course of Brainstem arteriovenous malformations and the influence of treatments on outcome. METHODS We reviewed a prospective series of 31 brainstem arteriovenous malformations. Demographic, morphological, and clinical characteristics were recorded. Factors determining initial and final outcomes (modified Rankin Scale), results of treatments (cure rates, complications), and disease course were analyzed. RESULTS Brainstem arteriovenous malformations were symptomatic and bled in 93% and 61% of cases, respectively. Examination was abnormal and initial modified Rankin Scale score was &gt; 3 in 71% and 86% of patients, respectively. The average follow-up time was 6.2 years, and 26% of patients rebled (5.9 %/y). Treatment modalities included conservative, radiosurgical, endovascular, surgical, and multimodality treatment in 13%, 58%, 35%, 16%, and 26% of cases, respectively. The obliteration rate was 60% overall and 39% after radiosurgery, 40% after embolization, and 75% after microsurgery, with respective complication-free cure rates of 71%, 50%, and 0%. Overall procedural mortality and morbidity were 2.3% and 18.6%, respectively. Final modified Rankin Scale score was &gt; 3 in 77% of cases. Neurological deterioration (35%) was related to treatment complications in 74% of cases with a negative impact of surgery (P = .04), palliative embolization (odds ratio = 16), and multimodality treatments (odds ratio = 24). Radiosurgery was inversely associated with worsening (odds ratio = 0.06). CONCLUSION Brainstem arteriovenous malformations require individualized treatment decisions. Single-modality treatments with a reasonable chance of complete cure and low complication rate (such as radiosurgery) should be favored.


2016 ◽  
Vol 28 (3) ◽  
pp. 284-289 ◽  
Author(s):  
C Ilozue ◽  
B Howe ◽  
S Shaw ◽  
K Haigh ◽  
J Hussey ◽  
...  

People living with HIV are surviving longer on successful antiretroviral therapy and obesity rates are increasing. We sought to determine the prevalence of being overweight or obese in a regional population of people living with HIV and to explore the demographic and clinical characteristics associated with obesity or being overweight. Data on patients attending three Northeast England clinics were collected including body mass index and demographics. The prevalence of being overweight (body mass index ≥ 25 kg/m2) or obese (body mass index ≥ 30 kg/m2) was determined and compared with regional population data. Associations between being overweight or obese and demographic and other data were further explored using logistic regression models. In 560 patients studied (median age 45 years, 26% Black-African and 69% male), 65% were overweight/obese and 26% obese, which is similar to the local population. However, 83% and 48% of Black-African women were overweight/obese or obese, respectively, with 11% being morbidly obese (body mass index > 40 kg/m2). In the multivariate analyses, the only factors significantly associated with obesity were Black-African race (adjusted odds ratio 2.78, 95% confidence interval 1.60–4.85) and type 2 diabetes (adjusted odds ratio 4.23, 95% confidence interval 1.81–9.91). Levels of obesity and overweight in people living with HIV are now comparable to the levels in the local population of Northeast England; however, the prevalence is significantly higher in Black-African women. Given the additional risk factors for cardiovascular disease inherent in people living with HIV, better strategies to prevent, identify and manage obesity in this population are needed.


2019 ◽  
Vol 15 (2) ◽  
pp. 167-174 ◽  
Author(s):  
Charlotte Zerna ◽  
Tyler Burley ◽  
Theresa L Green ◽  
Sean P Dukelow ◽  
Andrew M Demchuk ◽  
...  

Background and Purpose The modified Rankin Scale (mRS) is the most widely used primary outcome measure in acute stroke trials. However, substantial interobserver variability impairs outcome assessment as well as reduces power of clinical trials. Guided by the International Classification of Functioning, Disability and Health, we developed a comprehensive, hierarchical assessment tool (miFUNCTION) to address the shortcomings of the modified Rankin Scale and deliver a more thorough understanding of disability following stroke. Methods The initial construct validity of miFUNCTION was established in a pilot study of patients at an outpatient stroke prevention clinic that had been diagnosed with stroke within 60 days. To further assess criterion validity, miFUNCTION was compared against the modified Rankin Scale and other outcome measures within the Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times (ESCAPE) trial. Logistic regression analysis with miFUNCTION as an outcome was used to demonstrate the beneficial effect of endovascular treatment. Results The pilot study showed moderate inter-observer agreement (k = 0.585, p < 0.005) but near perfect correlation between miFUNCTION and modified Rankin Scale (ρ = 0.821, p < 0.05). The correlation of miFUNCTION and modified Rankin Scale was near perfect again in the ESCAPE trial (ρ = 0.944). Effect size of the multivariable models using modified Rankin Scale (adjusted odds ratio: 3.45, 95% confidence interval: 2.05–5.78) and miFUNCTION (adjusted odds ratio: 3.32, 95% confidence interval: 1.99–5.55) as an outcome measure for the ESCAPE trial patients was similar. Conclusions miFUNCTION is strongly associated with the degree of disability following stroke both in an outpatient setting and a clinical trial. Further work remains to assess sensitivity to change and to improve the inter-observer reliability of the scale.


2017 ◽  
Vol 13 (1) ◽  
pp. 45-52 ◽  
Author(s):  
Mark M. Mitsnefes ◽  
Aisha Betoko ◽  
Michael F. Schneider ◽  
Isidro B. Salusky ◽  
Myles Selig Wolf ◽  
...  

Background and ObjectivesHigh plasma concentration of fibroblast growth factor 23 (FGF23) is a risk factor for left ventricular hypertrophy (LVH) in adults with CKD, and induces myocardial hypertrophy in experimental CKD. We hypothesized that high FGF23 levels associate with a higher prevalence of LVH in children with CKD.Design, setting, participants, & measurementsWe performed echocardiograms and measured plasma C-terminal FGF23 concentrations in 587 children with mild-to-moderate CKD enrolled in the Chronic Kidney Disease in Children (CKiD) study. We used linear and logistic regression to analyze the association of plasma FGF23 with left ventricular mass index (LVMI) and LVH (LVMI ≥95th percentile), adjusted for demographics, body mass index, eGFR, and CKD-specific factors. We also examined the relationship between FGF23 and LVH by eGFR level.ResultsMedian age was 12 years (interquartile range, 8–15) and eGFR was 50 ml/min per 1.73 m2 (interquartile range, 38–64). Overall prevalence of LVH was 11%. After adjustment for demographics and body mass index, the odds of having LVH was higher by 2.53 (95% confidence interval, 1.28 to 4.97; P<0.01) in participants with FGF23 concentrations ≥170 RU/ml compared with those with FGF23<100 RU/ml, but this association was attenuated after full adjustment. Among participants with eGFR≥45 ml/min per 1.73 m2, the prevalence of LVH was 5.4%, 11.2%, and 15.3% for those with FGF23 <100 RU/ml, 100–169 RU/ml, and ≥170 RU/ml, respectively (Ptrend=0.01). When eGFR was ≥45 ml/min per 1.73 m2, higher FGF23 concentrations were independently associated with LVH (fully adjusted odds ratio, 3.08 in the highest versus lowest FGF23 category; 95% confidence interval, 1.02 to 9.24; P<0.05; fully adjusted odds ratio, 2.02 per doubling of FGF23; 95% confidence interval, 1.29 to 3.17; P<0.01). By contrast, in participants with eGFR<45 ml/min per 1.73 m2, FGF23 did not associate with LVH.ConclusionsPlasma FGF23 concentration ≥170 RU/ml is an independent predictor of LVH in children with eGFR≥45 ml/min per 1.73 m2.


Stroke ◽  
2021 ◽  
Vol 52 (1) ◽  
pp. 144-151
Author(s):  
Zuolu Liu ◽  
Nerses Sanossian ◽  
Sidney Starkman ◽  
Gilda Avila-Rinek ◽  
Marc Eckstein ◽  
...  

Background and Purpose: A survival advantage among individuals with higher body mass index (BMI) has been observed for diverse acute illnesses, including stroke, and termed the obesity paradox. However, prior ischemic stroke studies have generally tested only for linear rather than nonlinear relations between body mass and outcome, and few studies have investigated poststroke functional outcomes in addition to mortality. Methods: We analyzed consecutive patients with acute ischemic stroke enrolled in a 60-center acute treatment trial, the NIH FAST-MAG acute stroke trial. Outcomes at 3 months analyzed were (1) death; (2) disability or death (modified Rankin Scale score, 2–6); and (3) low stroke-related quality of life (Stroke Impact Scale<median). Relations with BMI were analyzed univariately and in multivariate models adjusting for 14 additional prognostic variables. Results: Among 1033 patients with acute ischemic stroke, average age was 71 years (±13), 45.1% female, National Institutes of Health Stroke Scale 10.6 (±8.3), and BMI 27.5 (±5.6). In both unadjusted and adjusted analysis, increasing BMI was linearly associated with improved 3-month survival ( P =0.01) odds ratios in adjusted analysis for mortality declined across the BMI categories of underweight (odds ratio, 1.7 [CI, 0.6–4.9]), normal (odds ratio, 1), overweight (0.9 [CI, 0.5–1.4]), obese (0.5, [CI, 0.3–1.0]), and severely obese (0.4 [CI, 0.2–0.9]). In unadjusted analysis, increasing BMI showed a U-shaped relation to poststroke disability or death (modified Rankin Scale score, 2–6), with odds ratios of modified Rankin Scale score, 2 to 6 for underweight, overweight, and obese declined initially when compared with normal weight patients, but then increased again in severely obese patients, suggesting a U-shaped or J-shaped relation. After adjustment, including for baseline National Institutes of Health Stroke Scale, modified Rankin Scale score 2 to 6 was no longer related to adiposity. Conclusions: Mortality and functional outcomes after acute ischemic stroke have disparate relations with patients’ adiposity. Higher BMI is linearly associated with increased survival; and BMI has a U-shaped or J-shaped relation to disability and stroke-related quality of life. Potential mechanisms including nutritional reserve aiding survival during recovery and greater frequency of atherosclerotic than thromboembolic infarcts in individuals with higher BMI.


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