Association of Time to Thrombolysis With Early Reperfusion After Alteplase and Tenecteplase in Patients With Large Vessel Occlusion.

BACKGROUND AND OBJECTIVES: Early treatment with intravenous alteplase increases the probability of lytic-induced reperfusion in large vessel occlusion (LVO) patients. The relationship of tenecteplase-induced reperfusion and the timing of thrombolytic administration has not been explored. In this study, we performed a comparative analysis of tenecteplase and alteplase reperfusion rates and assessed their relationship to the time of thrombolytic administration. METHODS: Patients who were initially treated with a thrombolytic within 4.5 hours of symptom onset were pooled from the Royal Melbourne Stroke Registry, EXTEND-IA, EXTEND-IA TNK, and EXTEND-IA TNK part 2 trials. The primary outcome, thrombolytic-induced reperfusion, was defined as the absence of retrievable thrombus or >50% reperfusion at initial angiographic assessment (or repeat CT perfusion/angiography). We compared the treatment effect of tenecteplase and alteplase through fixed-effects Poisson regression modelling. RESULTS: Among 846 patients included in the primary analysis, early reperfusion was observed in 173 (20%) patients (tenecteplase: 98/470 [21%], onset-to-thrombolytic time: 132 minutes [interquartile range (IQR): 99-170], and thrombolytic-to-assessment time: 61 minutes [IQR: 39-96]; alteplase: 75/376 [19%], onset-to-thrombolytic time: 143 minutes [IQR: 105-180], thrombolytic-to-assessment time: 92 minutes [IQR: 63-144]). Earlier onset-to-thrombolytic administration times were associated with an increased probability of thrombolytic-induced reperfusion in patients treated with either tenecteplase (adjusted risk ratio [aRR] 1.05 per 15 minutes [95% confidence interval (CI) 1.00-1.12] or alteplase (aRR 1.06 per 15 minutes [95% CI 1.00-1.13]). Tenecteplase remained associated with higher rates of reperfusion vs alteplase after adjustment for onset-to-thrombolytic time, occlusion site, thrombolytic-to-assessment time, and study as a fixed effect, (adjusted incidence rate ratio: 1.41 [95% CI 1.02-1.93]). No significant treatment-by-time interaction was observed (p = 0.87). DISCUSSION: In patients with LVO presenting within 4.5 hours of symptom onset, earlier thrombolytic administration increased successful reperfusion rates. Compared with alteplase, tenecteplase was associated with a higher probability of lytic-induced reperfusion, independent of onset-to-lytic administration times. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov Identifiers: NCT02388061, NCT03340493. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that among patients with LVO receiving a thrombolytic, reperfusion was more likely with tenecteplase than alteplase.

Tenecteplase Improves Reperfusion across Time in Large Vessel Stroke.

OBJECTIVE: Tenecteplase improves reperfusion compared to alteplase in patients with large vessel occlusions. To determine whether this improvement varies across the spectrum of thrombolytic agent to reperfusion assessment times, we performed a comparative analysis of tenecteplase and alteplase reperfusion rates. METHODS: Patients with large vessel occlusion and treatment with thrombolysis were pooled from the Melbourne Stroke Registry, and the EXTEND-IA and EXTEND-IA TNK trials. The primary outcome, thrombolytic-induced reperfusion, was defined as the absence of retrievable thrombus or >50% reperfusion at imaging reassessment. We compared the treatment effect of tenecteplase and alteplase, accounting for thrombolytic to assessment exposure times, via Poisson modeling. We compared 90-day outcomes of patients who achieved reperfusion with a thrombolytic to patients who achieved reperfusion via endovascular therapy using ordinal logistic regression. RESULTS: Among 893 patients included in the primary analysis, thrombolytic-induced reperfusion was observed in 184 (21%) patients. Tenecteplase was associated with higher rates of reperfusion (adjusted incidence rate ratio [aIRR] = 1.50, 95% confidence interval [CI] = 1.09-2.07, p = 0.01). Findings were consistent in patient subgroups with first segment (aIRR = 1.41, 95% CI = 0.93-2.14) and second segment (aIRR = 2.07, 95% CI = 0.98-4.37) middle cerebral artery occlusions. Increased thrombolytic to reperfusion assessment times were associated with reperfusion (tenecteplase: adjusted risk ratio [aRR] = 1.08 per 15 minutes, 95% CI = 1.04-1.13 vs alteplase: aRR = 1.06 per 15 minutes, 95% CI = 1.00-1.13). No significant treatment-by-time interaction was observed (p = 0.87). Reperfusion via thrombolysis was associated with improved 90-day modified Rankin Scale scores (adjusted common odds ratio = 2.15, 95% CI = 1.54-3.01) compared to patients who achieved reperfusion following endovascular therapy. INTERPRETATION: Tenecteplase, compared to alteplase, increases prethrombectomy reperfusion, regardless of the time from administration to reperfusion assessment. Prethrombectomy reperfusion is associated with better clinical outcomes. ANN NEUROL 2023;93:489-499.

Determining the sensitivity of emergency dispatcher and paramedic diagnosis of stroke: statewide registry linkage study.

Introduction: Correctly identifying people with suspected stroke is essential for ensuring rapid treatment. Our aims were to determine the sensitivity of emergency dispatcher and paramedic identification of patients with stroke, the factors associated with correct identification, and whether there were any implications for hospital arrival times. Methods: Observational study using patient-level data from the Australian Stroke Clinical Registry (2015-2017) linked with ambulance and emergency department records for the state of Victoria. The registry diagnosis was the reference standard to compare with the provisional diagnoses made by emergency services personnel classified as "suspected" and "not suspected" stroke/transient ischemic attack (TIA). Multivariable logistic and quintile regressions were used to determine factors associated with correct identification and timely arrival to hospital. Results: Overall, 4717 (64%) were matched to ambulance transport records (median age: 73 years, 43% female). Stroke/TIA was suspected in 56% of registrants by call-takers and 69% by paramedics. Older patients (75+ years) (adjusted odds ratio [aOR]: 0.61; 95% confidence interval [CI]: 0.49-0.75), females (aOR: 0.86; 95% CI: 0.75-0.99), those with severe stroke or intracerebral hemorrhage were less often suspected as stroke. Cases identified as stroke had a shorter arrival time to hospital (unadjusted median minutes: stroke, 54 [43, 72] vs not stroke, 66 [51, 89]). Conclusions: Emergency dispatchers and paramedics identified over half of patients with stroke in the prehospital setting. Important patient characteristics, such as being female and those having a severe stroke, were found that may enable refinement of prehospital ambulance protocols and dispatcher/paramedic education. Those correctly identified as stroke, arrived earlier to hospital optimizing their chances of receiving time-critical treatments.

Prehospital idarucizumab prior to intravenous thrombolysis in a mobile stroke unit.

BACKGROUND: Administration of intravenous idarucizumab to reverse dabigatran anticoagulation prior to thrombolysis for patients with acute ischemic stroke has been previously described, but not in the prehospital setting. The speed and predictability of idarucizumab reversal is well suited to prehospital treatment in a mobile stroke unit and allows patients with recent dabigatran intake to access reperfusion therapy. AIMS: To describe feasibility of prehospital idarucizumab administration prior to thrombolysis on the Melbourne mobile stroke unit. METHODS: The Melbourne mobile stroke unit is a specialized stroke ambulance servicing central metropolitan Melbourne, Australia and provides prehospital assessment, scanning and treatment with an integrated CT scanner and multidisciplinary stroke team. All cases were identified through the mobile stroke unit treatment registry since launch in November 2017. RESULTS: Of a total of n = 20 thrombolysis cases in the first 4 months of operation, three patients (15%) received intravenous idarucizumab 5 g for dabigatran reversal prior to thrombolysis. Mean time between idarucizumab administration and thrombolysis was approximately 10 minutes. Two of the three patients were shown to have large vessel occlusion on CTA in the mobile stroke unit and proceeded to endovascular thrombectomy. At 24 hours, only one patient had a small amount of asymptomatic petechial hemorrhage on follow-up imaging. All patients demonstrated substantial neurological recovery and were discharged to inpatient rehabilitation. CONCLUSIONS: Rapid treatment with prehospital administration of idarucizumab prior to thrombolysis using a mobile stroke unit is feasible and facilitates hyperacute treatment.

Ambulance Clinical Triage for Acute Stroke Treatment: Paramedic Triage Algorithm for Large Vessel Occlusion.

BACKGROUND AND PURPOSE: Clinical triage scales for prehospital recognition of large vessel occlusion (LVO) are limited by low specificity when applied by paramedics. We created the 3-step ambulance clinical triage for acute stroke treatment (ACT-FAST) as the first algorithmic LVO identification tool, designed to improve specificity by recognizing only severe clinical syndromes and optimizing paramedic usability and reliability. METHODS: The ACT-FAST algorithm consists of (1) unilateral arm drift to stretcher <10 seconds, (2) severe language deficit (if right arm is weak) or gaze deviation/hemineglect assessed by simple shoulder tap test (if left arm is weak), and (3) eligibility and stroke mimic screen. ACT-FAST examination steps were retrospectively validated, and then prospectively validated by paramedics transporting culturally and linguistically diverse patients with suspected stroke in the emergency department, for the identification of internal carotid or proximal middle cerebral artery occlusion. The diagnostic performance of the full ACT-FAST algorithm was then validated for patients accepted for thrombectomy. RESULTS: In retrospective (n=565) and prospective paramedic (n=104) validation, ACT-FAST displayed higher overall accuracy and specificity, when compared with existing LVO triage scales. Agreement of ACT-FAST between paramedics and doctors was excellent (κ=0.91; 95% confidence interval, 0.79-1.0). The full ACT-FAST algorithm (n=60) assessed by paramedics showed high overall accuracy (91.7%), sensitivity (85.7%), specificity (93.5%), and positive predictive value (80%) for recognition of endovascular-eligible LVO. CONCLUSIONS: The 3-step ACT-FAST algorithm shows higher specificity and reliability than existing scales for clinical LVO recognition, despite requiring just 2 examination steps. The inclusion of an eligibility step allowed recognition of endovascular-eligible patients with high accuracy. Using a sequential algorithmic approach eliminates scoring confusion and reduces assessment time. Future studies will test whether field application of ACT-FAST by paramedics to bypass suspected patients with LVO directly to endovascular-capable centers can reduce delays to endovascular thrombectomy.

Large Vessel Occlusion Scales Increase Delivery to Endovascular Centers Without Excessive Harm From Misclassifications.

BACKGROUND AND PURPOSE: Clinical large vessel occlusion (LVO) triage scales were developed to identify and bypass LVO to endovascular centers. However, there are concerns that scale misclassification of patients may cause excessive harm. We studied the settings where misclassifications were likely to occur and the consequences of these misclassifications in a representative stroke population. METHODS: Prospective data were collected from consecutive ambulance-initiated stroke alerts at 2 stroke centers, with patients stratified into typical (LVO with predefined severe syndrome and non-LVO without) or atypical presentations (opposite situations). Five scales (Rapid Arterial Occlusion Evaluation [RACE], Los Angeles Motor Scale [LAMS], Field Assessment Stroke Triage for Emergency Destination [FAST-ED], Prehospital Acute Stroke Severity scale [PASS], and Cincinnati Prehospital Stroke Severity Scale [CPSSS]) were derived from the baseline National Institutes of Health Stroke Scale scored by doctors and analyzed for diagnostic performance compared with imaging. RESULTS: Of a total of 565 patients, atypical presentations occurred in 31 LVO (38% of LVO) and 50 non-LVO cases (10%). Most scales correctly identified >95% of typical presentations but <20% of atypical presentations. Misclassification attributable to atypical presentations would have resulted in 4 M1/internal carotid artery occlusions, with National Institutes of Health Stroke Scale score ≥6 (5% of LVO) being missed and 9 non-LVO infarcts (5%) bypassing the nearest thrombolysis center. CONCLUSIONS: Atypical presentations accounted for the bulk of scale misclassifications, but the majority of these misclassifications were not detrimental, and use of LVO scales would significantly increase timely delivery to endovascular centers, with only a small proportion of non-LVO infarcts bypassing the nearest thrombolysis center. Our findings, however, would require paramedics to score as accurately as doctors, and this translation is made difficult by weaknesses in current scales that need to be addressed before widespread adoption.