Session Report: Intravenous Thrombolysis in Acute Ischemic Stroke

The evening session on day 2 of ESOC 2025 here in Helsinki, Finland on “Intravenous Thrombolysis in Acute Ischemic Stroke: Expanding Indications and Evidence” was chaired by Melinda Roaldsen from Tromsø, Norway and Bart Van Der Worp (Utrecht, Netherlands).

Gaspard Gerschenfeld (Paris, France) kicked off the session with “TIME TO TREATMENT WITH INTRAVENOUS TENECTEPLASE BEFORE THROMBECTOMY AND FUNCTIONAL OUTCOMES IN ACUTE ISCHEMIC STROKE”. He points out that the benefit of intravenous thrombolysis (IVT) with alteplase plus thrombectomy vs thrombectomy alone has been shown to be time dependent and up to now, there is little data on tenecteplase. The study aimed to determine whether the potential benefit associated with tenecteplase plus thrombectomy vs thrombectomy alone decreased with treatment time. In a retrospective pooled analysis of patients with anterior circulation large vessel occlusion stroke with known symptom onset and no contraindication to IVT treated with either Tenecteplase before thrombectomy (TETRIS registry) or thrombectomy alone (ETIS registry), the study assessed the influence of the expected symptom onset-to-thrombolysis time (OTT) on the association between treatment and better functional outcome (lower mRS scores at 3 months). In a total of 1,890 patients between 2015-2024, median expected OTT was 144 vs. 149 minutes . Overall, tenecteplase before thrombectomy was associated with better 3-month functional outcome (weighted common OR 1.53 ; P < 0.0001). Tenecteplase before thrombectomy remained significantly associated with better 3-month functional outcome up to an expected OTT of 190 minutes.

Overall there was no significant interaction of OTT with treatment effect. He concludes that compared to MT alone, tenecteplase before MT in routine clinical care is associated with better 3-month functional outcomes without significant interaction between the expected OTT and treatment effect. Next, Aravind Ganesh (Calgary, Canada) presented “OUTCOMES AFTER MINOR ISCHEMIC STROKE IN ELDERLY PATIENTS TREATED WITH INTRAVENOUS THROMBOLYSIS VERSUS STANDARD OF CARE IN THE TEMPO-2 TRIAL”. This post-hoc analysis of the TEMPO-2 trial analyzed 884 patients regarding outcomes and adverse events in patients assigned to tenecteplase (TNK) vs. non-thrombolytic standard of care aged >80 years and ≤80 years. Among the 884 patients in the ITT-analysis, 208 (23.5%) were >80 years old. Patients >80 years fared worse with TNK on the mRS responder analysis (54% with TNK vs 69% control, aRR:0.80). There was no significant difference in patients ≤80 years (77% vs 77%, aRR:1.01). In both age groups, patients assigned to TNK were more likely to achieve NIHSS 0 at 5-days/discharge (aRR ≤80 years: 1.14,1.05-1.24, >80 years: 1.22,1.07-1.40) and recanalisation of arterial occlusions (aRR ≤80: 2.05,1.59-2.64, >80 years: 2.81,2.23-3.53). Serious adverse events (SAEs) were more frequent with TNK among patients >80 years (RR:2.29), but were not accounted by hemorrhagic outcomes (e.g. symptomatic intracranial hemorrhage in one patient). He concludes that elderly patients with minor stroke and occlusion or perfusion lesion assigned to TNK were more likely to achieve recanalisation of occlusions and short-term neurological recovery, as were younger patients. However, patients >80 years assigned to TNK had worse 90-day outcomes with more frequent SAEs, but this was not driven by sICH and might perhaps be driven by stroke progression or stroke recurrence. All in all, these results argue against the use of TNK in mild strokes in elderly patients.

Thomas Payne from Parkville, Australia presented “MATERNAL AND FOETAL SAFETY OUTCOMES OF THROMBOLYTICS FOR ISCHAEMIC STROKE IN PREGNANCY: A SYSTEMATIC REVIEW AND AGGREGATED CASE SERIES”. He emphasises that the safety of intravenous thrombolytics (IVT) in pregnancy is largely unknown and guidelines recommend a benefit-risk evaluation. In a systematic review, 121 studies were included on thrombolytics for stroke and non-stroke indications during pregnancy with the aim to provide maternal and fetal safety outcomes. A total of 214 patients were included who were treated with thrombolytics during pregnancy, of whom 83 had an ischemic stroke. The rate of miscarriage/stillbirth in women receiving thrombolysis was higher than in the general population. All in all, 31 cases of fetal death were reported in women treated with thrombolysis. After thorough analysis, there were six cases (19%) in which fetal death was deemed likely to be causally related to thrombolytics. He concludes that miscarriage/stillbirth rates are higher in the thrombolysis population compared to the non-stroke population and further data are urgently needed to draw conclusions.

Cristina Del Valle Vargas (Badalona, Spain) presented “USE OF INTRAVENOUS THROMBOLYSIS IN EXTENDED TIME WINDOW, WITH OR WITHOUT THROMBECTOMY, FOR ACUTE ISCHEMIC STROKE: A MULTICENTER STUDY IN CATALONIA”. She points out that IVT in the extended time window guided by advanced imaging relies on low-moderate evidence. Data on IVT combined with mechanical thrombectomy (MT) in this context remain scarce. This study aimed to analyse the use of IVT in the extended time window and assessed its clinical benefit compared to the conventional window (<4.5h) using real-world data. In a prospective multicenter registry of stroke patients in Catalonia (CICAT), 7,143 patients were analysed for good functional outcome. A total of 539 patients received IVT in the extended time window (414 IVT, 125 IVT+MT). For IVT alone, good outcome (extended 41.6% vs. conventional 46.4%, p=0.064), mortality (both 12.9%), and sICH (3.4% vs. 2.7%, p=0.430) were comparable. For IVT+MT, good outcome (extended 40.7% vs. conventional 44.8%, p=0.352) and sICH (6.4% vs. 4.4%, p=0.287) were similar, but mortality was higher in the extended time window (25.0% vs. 16.6%, p=0.02). Age, diabetes, baseline mRS, NIHSS and ASPECTS, but not time-window group, were independently associated with poor outcome. She concludes that IVT in the extended time window without MT is a widely accepted policy in Catalunya, accounting for 7.5% of all IVT-patients. The data seem reassuring and are mostly in line with pivotal studies. More evidence is needed regarding the safety of IVT in the extended time window when MT is planned.

“Intravenous thrombolysis prior to endovascular treatment in posterior circulation occlusions; a patient pooled analysis of four randomised controlled trials” was presented by Robrecht Knapen (Maastricht, Netherlands) on behalf of the VERITAS collaboration. The benefit of IVT before endovascular treatment (EVT) in the posterior circulation remains uncertain. This study aimed to assess the impact of IVT before EVT on treatment outcomes in patients with vertebrobasilar occlusion and included data from four RCTs within the

VERITAS collaboration (BEST, BASICS, ATTENTION, and BAOCHE trial). Out of 988 patients, 556 patients were allocated for EVT and analysed. No significant differences were observed between patients treated with or without IVT prior to EVT in terms of mRS 0-3 at 3 months (47% vs 44%), mRS 0-2 (39% vs 32%), mortality (33% vs 38%), and sICH rates (6.3% vs 4.9%). Also, subgroup analyses did not reveal any differences. He concludes that the findings suggest that bridging IVT over EVT alone was safe but not associated with improved outcomes and might imply a shared regime with a careful patient selection e.g. opting for IVT in transferred patients with a presumed treatment delay or patients with distinctive characteristics favoring bridging-IVT.

Lina Palaiodimou (Athens, Greece) presented “INTRAVENOUS THROMBOLYSIS IN PATIENTS WITH ACUTE ISCHAEMIC STROKE TAKING TICAGRELOR AS MONOTHERAPY OR COMBINATION WITH OTHER ANTIPLATELET DRUG.”

The safety of ticagrelor pretreatment in acute ischemic stroke (AIS) patients receiving intravenous thrombolysis (IVT) is uncertain and largely based on case reports. This study evaluated safety and efficacy outcomes of IVT in AIS patients pretreated with ticagrelor and used data from the SITS-International Stroke Thrombolysis Registry. Patients on single (SAPT) or dual (DAPT) antiplatelet therapy with ticagrelor were compared to patients with aspirin SAPT or other DAPT.

A total of 45 ticagrelor (8 SAPT, 37 DAPT with aspirin) and 42,058 other antiplatelet pretreated AIS patients who received IVT were included. Also, 37 ticagrelor-DAPT patients were matched with 137 patients receiving any other-DAPT. Patients with ticagrelor-DAPT had a trend for higher proportions of sICH (16.2% vs. 5.8%, p=0.051) and parenchymal hemorrhage (27.0% vs 13.1%, p=0.050) but similar 3-month excellent functional outcome (40.5% vs. 48.9, p=0.367) and death (21.6% vs. 17.5%, p=0.568) compared to other-DAPT. She concludes that the observational data show a numerically higher risk of sICH and parenchymal hemorrhage after IVT in the ticagrelor-DAPT patients, but without a detrimental effect on 3-month clinical outcomes compared to any other-DAPT. Additional larger prospective studies are warranted to determine the safety of IVT in AIS patients pretreated with ticagrelor, especially using tenecteplase because the rate of its use compared to alteplase was low in this study.

Elise K. Kristensen (Tromsø, Norway) presented “FUNCTIONAL OUTCOMES OF THROMBOLYSIS VERSUS NO THROMBOLYSIS IN PATIENTS WITH MILD ISCHEMIC STROKE. A COMPARATIVE EFFECTIVENESS STUDY”. This study evaluated the effectiveness and safety of intravenous thrombolysis (IVT) in mild acute ischemic stroke (NIHSS score ≤5). A total of 1,736 IVT-treated patients were matched with 1,736 controls not treated with IVT. At 90 days follow-up, 68.4% of IVT-treated patients and 61.2% of controls had excellent functional outcome (mRS 0-1; OR 1.39, 95% CI 1.20-1.60, p<0.001). IVT was associated with a higher probability of achieving mRS scores 0-2 (OR 1.57, 95% CI 1.29-1.91, p<0.001) and overall lower mRS scores (OR 1.41, 95% CI 1.25-1.59, p<0.001). No significant differences in mortality were observed. In the IVT group, sICH occurred in 3.7% within 24 hours after treatment. She concludes that IVT was associated with favorable functional outcomes at 90 days in patients with mild acute ischemic stroke.

Nishita Singh (Winnipeg, Canada) completed the session with “IMPACT AND PREDICTORS OF SERIOUS ADVERSE EVENTS IN ALTEPLASE COMPARED TO TENECTEPLASE TRIAL: A SECONDARY ANALYSIS”. In this secondary analysis of the AcT trial, SAEs were recorded within 24 hours of treatment and classified by organ system using the Medical Dictionary for Regulatory Activities (MedDRA). The study focused on predictors of SAEs and their impact on mRS at 90 days and quality of life. Of all 1,577 enrolled patients, 219 (13.9%) had SAEs in the study. Patients with SAEs had higher NIHSS (median 11 vs. 9, p<0.01) and higher thrombectomy rates (29.2% vs. 50.2%, p<0.01) than those without SAEs. SAEs had a reasonable effect on mRS-shift with an aOR of 4.43 (95%CI 3.05-6.43) for any SAE. Nervous system disorders were the most common SAE type (58%), including stroke worsening (26.7%) and intracranial hemorrhage (25%). No significant differences were observed in SAE distribution by organ class or SAE term between tenecteplase and alteplase. Baseline NIHSS, large vessel occlusion, ASPECTS score and cerebral atrophy were significant predictors of SAE occurrence. She concludes that there were no differences in SAE incidence and type between tenecteplase and alteplase, which is very reassuring for clinical practice. SAEs were associated with worse functional outcomes regardless of intravenous thrombolytic type.

This evening session of day 2 gave a real breath of fresh air on the hottest research topics on intravenous thrombolysis in acute ischemic stroke. All presenters and the audience will now prepare for the final session of day 2, the vibrant ESOC party held at Finlandia Hall in Helsinki, Finland.