Welcome to the ESOC 2021 Virtual Conference Calendar

Group Name

CEREHETIS Investigators

Background And Aims

Neuroprotection with Cerebrolysin could mitigate reperfusion injury and hemorrhagic transformation (HT) in acute ischemic stroke (AIS).

Methods

This was a prospective, randomized, open-label, active control, multicenter, 1:2 parallel-group phase IIIb pilot study. Cerebrolysin (30 mL/day/14 days) was started concurrently with alteplase, 0.9 mg/kg in 117 patients, whereas 201 control patients were given alteplase alone. The patients were followed in 24 h (V1), on day 7 (V2), 14 (V3), and 90 (V4). The primary outcome was the rate of any and symptomatic HT at V1-3. The secondary endpoints were evaluation of safety (screening for adverse events at V1-V3) and functional outcome measured with the National Institutes of Health Stroke Scale (NIHSS) at V1-3, and modified Rankin scale (mRS) at V4. The favorable functional outcome was considered as a mRS score of ≤2. Odds ratio (OR) and number needed to treat (NNT) with 95% confidence intervals (CI) were calculated.

Results

Any HT: OR, 0.417 (95% CI, 0.200-0.871; p = 0.020); NNT (benefit), 10.86 (95% CI, 5.50-420.68). Symptomatic HT: OR, 0.171 (95% CI, 0.040-0.726; p = 0.017); NNT (benefit), 15.65 (95% CI, 8.33-129.10). No serious adverse event attributed to Cerebrolysin occurred. The groups did not differ in NIHSS score at V1 and V2, but it decreased noticeably in the case arm at V3 (p = 0.032). The mRS score remained similar in both groups at V4.

Conclusions

The early add-on of Cerebrolysin to reperfusion therapy was safe, and decreased the HT rate and neurological deficit, but that was of no impact on functional outcome.

Trial Registration Number

ISRCTN87656744

Background And Aims

Current guidelines recommend against the use of intravenous tissue-type plasminogen activator (IV tPA) alteplase in acute ischemic stroke (AIS) patients who are taking non-vitamin K antagonist oral anticoagulants (NOACs). However, there is limited data on the safety and outcomes of IV tPA in these patients.

Methods

Using data from the American Heart Association Get With The Guidelines-Stroke (GWTG-Stroke) Registry, we examined the outcomes of IV tPA use among AIS patients on NOACs versus those not on anticoagulation from 1752 hospitals between April 2015 and March 2020.

Results

Of the 163,038 AIS patients who were treated with IV tPA within the 4.5-hour treatment window, 2207 (1.4%) were on NOAC therapy. Patients taking NOACs were older, had higher prevalence of cardiovascular comorbidities, and experienced more severe strokes (NIHSS median 10 versus 7; p<0.0001), compared with those not on anticoagulation. Relative to those not, patients on NOACs had an unadjusted risk of symptomatic intracranial hemorrhage (sICH) of 3.7% versus 3.2% and in-hospital mortality of 6.3% versus 4.9%. However, after adjusting for baseline clinical factors, these risks were not statistically different (sICH: aOR, 0.88 [95%CI, 0.70-1.10]; in-hospital mortality: aOR, 0.84 [95%CI, 0.69-1.01]). Rather, patients on NOACs were more likely to ambulate independently (aOR, 1.25 [95%CI, 1.12-1.40]), be discharged home (aOR, 1.17 [95%CI, 1.06-1.29]), and have a modified Rankin Scale of 0-2 (aOR, 1.27 [95%CI, 1.11-1.45]).

Conclusions

Treatment with IV tPA appears to be well tolerated in AIS patients taking NOACs; however, findings should be corroborated among patients whose time of last NOAC dose is known and reported.

Trial Registration Number

Not applicable

Group Name

on behalf of the TRISP collaborators

Background And Aims

In recent RCTs intravenous thrombolysis (IVT) beyond 4.5 hours of stroke onset was safe and effective, if patient selection was based on distinct imaging criteria. However, real-world data on safety of IVT beyond 4.5 hours are scarce. We aimed at determining the probability of symptomatic intracranial hemorrhage (sICH), poor functional outcome and mortality in patients treated in the extended time window outside of a RCT setting.

Methods

Data of ischemic stroke patients treated with IVT from the prospective ThRombolysis in Ischaemic Stroke Patients (TRISP) registry were used. We compared patients treated between 0-4.5 hours with those treated >4.5-9 hours after stroke onset using sICH (ECASS-II-criteria), poor 3-month outcome (modified Rankin Scale 3-6) and mortality as outcomes. We calculated adjusted OR with 95%-CI using logistic regression models.

Results

Of 15’827 patients, 15’164 (95.8%) received IVT within 4.5 hours and 663 (4.2%) between >4.5-9 hours. Median age (73 vs 73) and median NIHSS (8 vs 8) was alike in both groups. The probability of sICH (OR_adjusted 0.80[0.53-1.22]), poor 3-month outcome (OR_adjusted 0.96[0.79-1.17]) and mortality (OR_adjusted 0.81[0.61-1.07]) did not differ significantly. No independent association was found between increasing stroke-onset to treatment intervals (by 30 minutes) and any outcome.

Conclusions

IVT-treatment in stroke patients between >4.5-9 hours after stroke onset was safe and not associated with worse functional outcome or mortality in this large real-world dataset. Our results suggest that in experienced stroke centers, current methods of patient selection for IVT in the extended time window seem to be appropriate.

Trial Registration Number

Not applicable

Group Name

on behalf of the TRISP collaborators

Background And Aims

In recent RCTs intravenous thrombolysis (IVT) beyond 4.5 hours of stroke onset was safe and effective, if patient selection was based on distinct advanced imaging criteria. However, in real-life, the impact of imaging-based patient selection for IVT >4.5 hours on outcomes is ambiguous. We aimed at comparing outcomes of patients treated with IVT between >4.5-9 hours dependent on the type of baseline imaging.

Methods

Stroke patients treated with IVT >4.5-9 hours after stroke onset from the prospective ThRombolysis in Ischaemic Stroke Patients (TRISP) registry were included. We compared (i) patients with advanced imaging to those without and (ii) patients with CT-Perfusion (CTP) to those with MR-Perfusion or MR-DWI/FLAIR (MRI). Outcomes were sICH (ECASS-II-criteria), poor 3-month outcome (mRS 3-6) and mortality. We calculated adjusted OR with 95%-CI using logistic regression models.

Results

Of 652 patients treated with IVT between >4.5-9 hours after stroke onset, 454 (69.6%) had advanced imaging (210 MRI; 244 CTP) and 198 (30.4%) did not. The occurrence of basilar occlusion was evenly distributed (2.5% vs 3.5%). With advanced imaging the probability of death was independently lower than without advanced imaging (9.7% vs. 20.2%, OR_adjusted 0.47[0.26-0.86]), but not of sICH (OR_adjusted 1.39[0.55-3.52]) and poor outcome OR_adjusted 0.85[0.54-1.33]). No independent association was found between the two types of advanced imaging and any outcome.

Conclusions

Patient selection for IVT in the extended time window based on advanced imaging was not associated with better functional outcome, but mortality was independently lower. Moreover, the type of advanced imaging (CTP or MRI) does not seem to matter.

Trial Registration Number

Not applicable

Group Name

Catalan Stroke Code and Reperfusion Consortium (Cat-SCR Consortium)

Background And Aims

To analyze the factors that determine the treatment with intravenous thrombolysis (IVT) in patients with minor ischemic stroke (NIHSS ≤ 5) in our population.

Methods

Data were obtained from CICAT: prospective, government-mandated, population-based registry of stroke code patients in Catalonia. We selected patients diagnosed with ischemic stroke and NIHSS ≤ 5 at hospital admission from January 2016 to October 2020. We excluded patients with a baseline modified Rankin scale(mRS) ≥ 3, absolute contraindication for IVT, unknown stroke onset or admitted to hospital beyond 4.5 h.

Results

We analyzed 2868 patients, 1396 (48.7%) received IVT, 22(1.6%) had a symptomatic hemorrhagic transformation. Patients treated with IVT were younger (68 vs 69 years, p=0.037), more frequently women (53% vs 47%, p = 0.001), had higher NIHSS (4 vs 2, p=0.001), arrived earlier to hospital (81 vs 91 min, p=0.001) and had more large vessel occlusion (LVO, 13% vs 2% p < 0.001). For NIHSS 4-5, 2-3 and 0-1, the proportion of patients treated with IVT and mean door-to-needle time were respectively: 85%/41%/16% p<0.001 and 48/51/58 min p=0.003. In adjusted multivariate analysis NIHSS (OR 2.7 CI 95% 2.5-2.9) and LVO(OR 10.3 CI 95% 6.5-16.4) were the variables more strongly associated with IVT. The effect of LVO was more important in patients with NIHSS 0-1(OR 17.7 CI95% 7.7-40.9) and NIHSS 2-3(OR 8.9 CI 4.9-16.4) than NIHSS 4-5(OR 3.6 CI95% 1.4- 9.1).

Conclusions

NIHSS and LVO were strong predictors for IVT in minor stroke patients. The effect of diagnosing LVO was more important in patients with low NIHSS

Group Name

Lars Kellert on behalf of the GSR investigators.

Niaz Ahmed on behalf of the SITS investigators.

Background And Aims

Treatment of large vessel occlusion (LVO) in patients presenting with mild neurological deficits (minor strokes with NIHSS ≤5) is still a matter of debate. The main purpose of this study was to compare the outcome of these patients treated with intravenous thrombolysis (IVT) plus/minus mechanical thrombectomy(MT).

Methods

Patients enrolled between 06/2015 and 12/2019 in the German Stroke Registry-Endovascular Treatment(GSR-ET) and the Safe Implementation of Thrombolysis in Stroke (SITS)-registry were analyzed. Minor LVO-stroke patients were compared using propensity score matching (PSM). Primary outcomes were the safety, technical and clinical efficacy of IVT plus/minus MT including rate of successful reperfusion using the modified Thrombolysis In Cerebral Infarction (mTICI) score (2b-3) and good functional outcome at 3-months follow-up (modified Rankin Scale (mRS) of 0-2).

Results

676(9.6%) out of the GSR-ET presented with minor strokes. Among these, 272 GSR-ET-patients – all treated with IVT (age 68.6±14.0 years, 43.4% female, premorbid mRS(pmRS) 0 (0-0), NIHSS 4 (2-5)) were compared to 272 SITS-patients (69.4±13.7, 43.4% females, pmRS 0 (0-0), NIHSS 4 (2-5)). Successful reperfusion in GSR-ET-patients was achieved in 81.6%. Good functional outcome (67.3% versus69.5%, p=0.795), mortality (5.1% versus6.6%, p=0.207) and rate of intracranial hemorrhage (ICH) (12.5% versus8.8%, p=0.308) were comparable between both groups. After PSM for 624 GSR-ET-patients (IVT-rate 56.7%) and 624 SITS-patients independent predictors for good outcome were age, pmRS, NIHSS, IVT-treatment and occurrence of ICH.

Conclusions

Our study demonstrates similar effectiveness of IVT alone compared to MT plus/minus IVT in minor LVO-stroke patients. There is an urgent need for randomized controlled trials in this stroke field.

Trial Registration Number

Not applicable

Background And Aims

Symptomatic intraparenchymal hemorrhage (sICH) and major bleeding can be fatal complications of intravenous thrombolysis (IVT) for acute ischemic stroke. We investigated the impact of early fibrinogen depletion after IVT on major bleeding events.

Methods

This multicenter observational study enrolled consecutive patients receiving IVT for acute ischemic stroke at 6 Italian centers, undergoing fibrinogen concentration assessment at baseline, 2 hours and 6 hours after IVT. Fibrinogen depletion was defined as a reduction below 200 mg/dl after 2 hours from IVT, or as a reduction below 50% of baseline fibrinogen levels after 2 hours from IVT. Main outcomes were (i) sICH according to National Institute of Neurological Disorders and Stroke criteria, and (ii) major bleeding.

Results

Overall, 1678 patients were included. sICH (n=116) and major bleeding (n=297) were associated with lower prevalence of good functional recovery (p<0.001). Despite similar fibrinogen levels at admission, fibrinogen depletion after 2 hours from IVT was more common in people with sICH and major bleeding. In the backward stepwise multivariable logistic regression model, fibrinogen depletion remained a significant predictor of sICH (OR 1.55, 95%CI 1.04-2.32) and major bleeding (OR 1.36, 95%CI 1.03-1.8).

Conclusions

Fibrinogen depletion significantly increases the risk of sICH and major bleeding after IVT for acute ischemic stroke. Routine assessment of fibrinogen might be considered to stratify the risk of ICH.

Group Name

on behalf of the EXTEND-IA TNK Investigators

Background And Aims

Assessment of tenecteplase (TNK) in the elderly is limited. We assessed the safety and efficacy of TNK at 0.40 and 0.25mg/kg dosing in patients >80 years with large vessel occlusion.

Methods

Patients were enrolled in parts 1 and 2 of the EXTEND-IA TNK trials. 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 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

Of the 502 patients included in analysis, 251 patients (50%) were randomized to TNK 0.25mg/kg, 150 (30%) randomized to TNK 0.40mg/kg and 101 (20%) randomized to alteplase. In patients >80 years (n=137), TNK 0.25mg/kg was associated with improved 90-day mRS (aOR=2.70, 95%CI: 1.23-5.94) and reduced mortality (aOR=0.34, 95%CI: 0.13-0.91) versus 0.40mg/kg dosing, and improved 90-day mRS (aOR=2.28, 95%CI: 1.03-5.05) versus alteplase. No difference in 90-day mRS or mortality was detected between alteplase and TNK 0.40mg/kg. Symptomatic ICH was observed in 4 patients treated with TNK 0.40mg/kg, one patient treated with alteplase and zero patients treated with TNK 0.25mg/kg (p=0.01). In patients ≤80 years, no differences in 90-day mRS, mortality, or symptomatic ICH was observed between TNK 0.25mg/kg, TNK 0.40mg/kg, and alteplase.

Conclusions

TNK 0.25mg/kg was associated with improved 90-day mRS and reduced mortality in patients >80 years of age. No differences between the dosing groups was observed in younger patients.

Trial Registration Number

EXTEND-IA TNK Part 1: NCT02388061

EXTEND-IA TNK Part 2: NCT03340493