Intravenous Thrombolysis 4.5-9 Hours After Stroke Onset: A Cohort Study from the TRISP Collaboration.

OBJECTIVE: To investigate the safety and effectiveness of intravenous thrombolysis (IVT) >4.5-9 hours after stroke onset, and the relevance of advanced neuroimaging for patient selection. METHODS: Prospective multicenter cohort study from the ThRombolysis in Ischemic Stroke Patients (TRISP) collaboration. Outcomes were symptomatic intracranial hemorrhage, poor 3-month functional outcome (modified Rankin scale 3-6) and mortality. We compared: (i) IVT >4.5-9 hours versus 0-4.5 hours after stroke onset and (ii) within the >4.5-9 hours group baseline advanced neuroimaging (computed tomography perfusion, magnetic resonance perfusion or magnetic resonance diffusion-weighted imaging fluid-attenuated inversion recovery) versus non-advanced neuroimaging. RESULTS: Of 15,827 patients, 663 (4.2%) received IVT >4.5-9 hours and 15,164 (95.8%) within 4.5 hours after stroke onset. The main baseline characteristics were evenly distributed between both groups. Time of stroke onset was known in 74.9% of patients treated between >4.5 and 9 hours. Using propensity score weighted binary logistic regression analysis (onset-to-treatment time >4.5-9 hours vs onset-to-treatment time 0-4.5 hours), the probability of symptomatic intracranial hemorrhage (ORadjusted 0.80, 95% CI 0.53-1.17), poor functional outcome (ORadjusted 1.01, 95% CI 0.83-1.22), and mortality (ORadjusted 0.80, 95% CI 0.61-1.04) did not differ significantly between both groups. In patients treated between >4.5 and 9 hours, the use of advanced neuroimaging was associated with a 50% lower mortality compared with non-advanced imaging only (9.9% vs 19.7%; ORadjusted 0.51, 95% CI 0.33-0.79). INTERPRETATION: This study showed no evidence in difference of symptomatic intracranial hemorrhage, poor outcome, and mortality in selected stroke patients treated with IVT between >4.5 and 9 hours after stroke onset compared with those treated within 4.5 hours. Advanced neuroimaging for patient selection was associated with lower mortality. ANN NEUROL 2023;94:309-320.

Intravenous Thrombolysis in Patients With Ischemic Stroke Aged ≥90 Years: A Cohort Study From the TRISP Collaboration.

BACKGROUND: The probability to receive intravenous thrombolysis (IVT) for treatment of acute ischemic stroke declines with increasing age and is consequently the lowest in very elderly patients. Safety concerns likely influence individual IVT treatment decisions. Using data from a large IVT registry, we aimed to provide more evidence on safety of IVT in the very elderly. METHODS: In this prospective multicenter study from the TRISP (Thrombolysis in Ischemic Stroke Patients) registry, we compared patients ≥90 years with those <90 years using symptomatic intracranial hemorrhage (ECASS [European Cooperative Acute Stroke Study]-II criteria), death, and poor functional outcome in survivors (modified Rankin Scale score 3-5 for patients with prestroke modified Rankin Scale score ≤2 and modified Rankin Scale score 4-5 for patients prestroke modified Rankin Scale ≥3) at 3 months as outcomes. We calculated adjusted odds ratio with 95% CI using logistic regression models. RESULTS: Of 16 974 eligible patients, 976 (5.7%) were ≥90 years. Patients ≥90 years had higher median National Institutes of Health Stroke Scale on admission (12 versus 8) and were more often dependent prior to the index stroke (prestroke modified Rankin Scale score of ≥3; 45.2% versus 7.4%). Occurrence of symptomatic intracranial hemorrhage (5.7% versus 4.4%, odds ratioadjusted 1.14 [0.83-1.57]) did not differ significantly between both groups. However, the probability of death (odds ratioadjusted 3.77 [3.14-4.53]) and poor functional outcome (odds ratioadjusted 2.63 [2.13-3.25]) was higher in patients aged ≥90 years. Results for the sample of centenarians (n=21) were similar. CONCLUSIONS: The probability of symptomatic intracranial hemorrhage after IVT in very elderly patients with stroke did not exceed that of their younger counterparts. The higher probability of death and poor functional outcome during follow-up in the very elderly seems not to be related to IVT treatment. Very high age itself should not be a reason to withhold IVT.

Thrombolysis in stroke patients with elevated inflammatory markers.

OBJECTIVE: To investigate the prognostic value of white blood cell count (WBC) on functional outcome, mortality and bleeding risk in stroke patients treated with intravenous thrombolysis (IVT). METHODS: In this prospective multicenter study from the TRISP registry, we assessed the association between WBC on admission and 3-month poor outcome (modified Rankin Scale 3-6), mortality and occurrence of symptomatic intracranial hemorrhage (sICH; ECASS-II-criteria) in IVT-treated stroke patients. WBC was used as continuous and categorical variable distinguishing leukocytosis (WBC > 10 × 109/l) and leukopenia (WBC < 4 × 109/l). We calculated unadjusted/ adjusted odds ratios with 95% confidence intervals (OR [95% CI]) with logistic regression models. In a subgroup, we analyzed the association of combined leukocytosis and elevated C-reactive protein (CRP > 10 mg/l) on outcomes. RESULTS: Of 10,813 IVT-treated patients, 2527 had leukocytosis, 112 leukopenia and 8174 normal WBC. Increasing WBC (by 1 × 109/l) predicted poor outcome (ORadjusted 1.04[1.02-1.06]) but not mortality and sICH. Leukocytosis was independently associated with poor outcome (ORadjusted 1.48[1.29-1.69]) and mortality (ORadjusted 1.60[1.35-1.89]) but not with sICH (ORadjusted 1.17[0.94-1.45]). Leukopenia did not predict any outcome. In a subgroup, combined leukocytosis and elevated CRP had the strongest association with poor outcome (ORadjusted 2.26[1.76-2.91]) and mortality (ORadjusted 2.43[1.86-3.16]) when compared to combined normal WBC and CRP. CONCLUSION: In IVT-treated patients, leukocytosis independently predicted poor functional outcome and death. Bleeding complications after IVT were not independently associated with leukocytosis.

Efficacy and safety of bridging thrombolysis initiated before transfer in a drip-and-ship stroke service.

OBJECTIVE: Data regarding the efficacy and safety of bridging thrombolysis (BT) initiated before transfer for evaluation of endovascular therapy is heterogeneous. We, therefore, analyse efficacy and safety of BT in patients treated within a drip-and-ship stroke service. METHODS: Consecutive adult patients suffering from acute ischaemic stroke and large-vessel occlusions (LVO) transferred to our comprehensive stroke centre for evaluation of endovascular therapy in 2017-2020 were identified from a local prospective stroke database and categorised according to BT and no-BT. BT was defined as intravenous thrombolysis initiated before transfer. LVO was assessed before and after transfer. Functional outcome before stroke and at 3 months using the modified Rankin scale (mRS) was determined. Excellent outcome was defined as mRS 0-1 or return to prestroke mRS. For safety analysis, intracranial haemorrhages and mortality at 3 months were analysed. Main analysis was limited to patients with anterior circulation stroke. RESULTS: Of N=714 patients, n=394 (55.2%) received BT. More patients in the BT group with documented LVO before transfer recanalised without endovascular therapy (n=46, 11.7%) than patients who did not receive BT before transfer (n=4, 1.3%, p<0.001). In multivariate analysis, BT was the strongest independent predictor of early recanalisation (adjusted OR 10.9, 95% CI 3.8 to 31.1, p<0.001). BT tended to be an independent predictor of an excellent outcome at 3 months (adjusted OR 1.38, 95% CI 0.97 to 1.96, p=0.077). There were no differences in safety between the BT and no-BT groups. CONCLUSIONS: BT initiated before transfer was a strong independent predictor of early recanalisation.

Trimethylamine-N-Oxide Levels Are Similar in Asymptomatic vs. Symptomatic Cerebrovascular Atherosclerosis.

Introduction: Trimethylamine-N-oxide (TMAO) is correlated with atherosclerosis and vascular diseases such as coronary heart disease and ischemic stroke. The aim of the study was to investigate whether TMAO levels are different in symptomatic vs. asymptomatic cerebrovascular atherosclerosis. Methods: This was a prospective, case-control study, conducted at a tertiary care university hospital. Patients were included if they had large-artery atherosclerosis (TOAST criteria). Symptomatic patients with ischemic stroke were compared with asymptomatic patients. As primary endpoint, TMAO levels on admission were compared between symptomatic and asymptomatic patients. Univariable analysis was performed using Mann-Whitney U test and multivariable analysis using binary logistic regression. TMAO values were adjusted for glomerular filtration rate (GFR), age, and smoking. Results: Between 2018 and 2020, 82 symptomatic and asymptomatic patients were recruited. Median age was 70 years; 65% were male. Comparing symptomatic (n = 42) and asymptomatic (n = 40) patients, no significant differences were found in univariable analysis in TMAO [3.96 (IQR 2.30-6.73) vs. 5.36 (3.59-8.68) µmol/L; p = 0.055], GFR [87 (72-97) vs. 82 (71-90) ml/min*1.73 m2; p = 0.189] and age [71 (60-79) vs. 69 (67-75) years; p = 0.756]. In multivariable analysis, TMAO was not a predictor of symptomatic cerebrovascular disease after adjusting for age and GFR [OR 1.003 (95% CI: 0.941-1.070); p = 0.920]. In a sensitivity analysis, we only analyzed patients with symptomatic stenosis and excluded patients with occlusion of brain-supplying arteries. Again, TMAO was not a significant predictor of symptomatic stenosis [OR 1.039 (0.965-1.120), p = 0.311]. Conclusion: TMAO levels could not be used to differentiate between symptomatic and asymptomatic cerebrovascular disease in our study.

Patient profiles contribute to differences in quality metrics of stroke centers.

OBJECTIVE: To examine this association by comparing patient profiles in 2 closely affiliated hospitals and by examining their association with quality metrics. METHODS: We performed a retrospective cohort study comparing a university level comprehensive stroke centers (CSC) with its teaching hospital and local stroke unit (LSU) using routinely collected quality assurance data over a 2 year period. Both hospitals were closely affiliated, shared important resources and medical staff rotated amongst both hospitals. We compared patient profiles as well as internationally recognized quality metrics and examined the association of profiles with quality metrics. RESULTS: A total of 2,462 patients were treated in the CSC and 726 in the LSU. The LSU had a longer door-to-image and door-to-needle times. Rate of systemic thrombolysis was lower in the LSU. Patient profiles differed significantly and were associated with door-to-image and door-to-needle times as well as intravenous thrombolysis rates, even when adjusted for stroke service level. The diagnostic procedures for stroke work-up were similar. Discharge management differed strongly. CONCLUSION: Although LSUs and CSCs are the primary care providers in their respective regions, differences in patient profiles may contribute to differences in performance parameters. Adjusting for patient profiles may improve the comparability of the quality of stroke care provided by hospitals belonging to different stroke service levels.