by Christian Boehme, ESO Social Media and PR Committee
Department of Neurology, Medical University of Innsbruck, Austria
Twitter: @chris7ianb
On Day 2 of the 10th anniversary of ESOC 2024 in Basel, Urs Fischer invited for a morning run at 7 am where lots of early bird-healthy strokeologists took part to recharge energy for a further exciting day here in Basel.
Nikola Sprigg (Nottingham, United Kingdom) and Daniel Strbian (Helsinki, Finland) chaired this second large clinical trials session.
Xia Wang from Barangaroo, Australia sparked off the session with TIMING OF BP LOWERING TO MITIGATE HEMATOMA EXPANSION IN INTRACEREBRAL HEMORRHAGE: IPD POOLED ANALYSIS OF 4 INTERACT TRIALS.
The aim of the study was to determine effects of BP lowering in reducing hematoma growth in ICH in relation to the timing of treatment initiation. Outcomes were hematoma growth at 24 hours in absolute and relative growth. BP lowering had a significant effect on relative hematoma growth predominantly if treated to target within 2.5 hours of onset and in low ICH score events. The BP lowering effect on hematoma growth is related to timing of systolic BP reduction (“the earlier, the better”) and to severity of ICH (“the milder, the better”). BP lowering treatment is likely most effective in patients with milder acute ICH when initiated early (within 2 hours) and when done intensively (aiming for an SBP target <140 mmHg).
In clinical practice, Xia points out that BP control might be faster when not in the scope of a trial because of the time-consuming randomization process. The INTERACT 4 results will be presented later this morning so stay tuned.
Next, Yongjun Wang (Beijing, China) presented the results of the ORIGINAL trial: TENECTEPLASE VERSUS ALTEPLASE IN CHINESE PATIENTS WITH ACUTE ISCHAEMIC STROKE (ORIGINAL): A MULTICENTRE RANDOMISED PHASE III STUDY. The trial assessed if tenecteplase was non-inferior to alteplase regarding favorable functional outcome in acute ischemic stroke in Chinese patients when administered <4.5 hours after onset. As a distinct inclusion criterion, the study included NIHSS of 1-25 points at admission. The trial demonstrated that tenecteplase was non-inferior to alteplase in reaching an mRS 0-1 after 3 months, the findings were consistent across prespecified subgroups, including baseline NIHSS, age, time to administration, gender, comorbidities and thrombectomy use. Safety outcomes were also comparable. Therefore, these results are in line with previous trials evaluating tenecteplase use in acute ischemic stroke.
Valerian Altersberger, a local here from Basel, Switzerland presented BRIDGING THROMBOLYSIS WITH TENECTEPLASE VERSUS ENDOVASCULAR TREATMENT ALONE FOR LARGE-VESSEL ANTERIOR CIRCULATION STROKE. The study used a target trial emulation of SWIFT DIRECT and EXTEND-IA TNK Part 1&2 using 0.25 mg/kg and 0.40 mg/kg of tenecteplase. The study which included 427 patients, showed no benefit of bridging thrombolysis with tenecteplase on increased rates of functional outcomes compared to direct mechanical thrombectomy but it resulted in improved functional outcome on the full ordinal mRS and in higher frequency of freedom of disability. The effect was predominantly driven by the lower mRS grades. The results remained unchanged when only including patients who underwent treatment with tenecteplase in a dosage of 0.25 mg/kg. The improvement of outcomes was more pronounced in patients where onset-to (expected) IVT time was <140 minutes. Valerian points out that external validation is needed and a RCT (DIRECT-TNK) is underway to answer this question.
Fabiano Cavalcante (Amsterdam, Netherlands) presented results from the MR CLEAN-NO IV trial: INTRAVENOUS THROMBOLYSIS BEFORE ENDOVASCULAR TREATMENT IN PATIENTS WITH CAROTID TANDEM LESIONS: MR CLEAN-NO IV RANDOMIZED CLINICAL TRIAL RESULTS. He highlights the fact that tandem lesions affect 15% of all patients undergoing EVT. Tandem lesion was defined as ipsilateral flow-limiting lesion (>50% stenosis, dissection, occlusion) and the primary outcome was mRS score at 90 days. The study included 88 patients with tandem lesions of the 539 patients in the MR CLEAN-NO IV trial. Tandem lesions significantly worsened functional outcomes on the mRS shift analysis as well as rates of favorable functional outcome and increased the risk for any ICH, but not statistically significant for sICH. Regarding treatment, IVT before EVT was less effective in patients with tandem lesions and more effective in patients without tandem lesions, whereby rates of ICH and sICH were similar. In recognition of these data, we are excited to hear the IRIS pooled results later today.
Santiago Ortega-Gutierrez (Iowa City, United States) followed with ENDOVASCULAR THROMBECTOMY FOR LARGE ISCHEMIC STROKES WITH TANDEM LESIONS: A SECONDARY ANALYSIS OF THE SELECT2 TRIAL. The study aimed to compare the effectiveness and safety outcomes of EVT with medical management in patients with extracranial ICA occlusions and large ischemic core. In this secondary analysis of the SELECT2-trial, 62 of 352 patients in the SELECT2 trial with complete occlusion of the extracranial ICA in addition to intracranial anterior LVO (including M2) were included.
The study found a shift in the 90-day mRS score towards better outcomes in the EVT group compared to medical management. Independence at 90 days occurred in 38% of patients in the EVT group compared to 8% in the medical management group. Risk of hemorrhagic transformation was higher in the EVT group mainly driven by an increase of petechial hemorrhage. Santiago concludes that, in patients with extracranial ICA occlusions and large ischemic core in addition to intracranial LVO, EVT appears to improve functional outcomes without major safety concerns compared to medical management. This study advocates for more extensive research to define the optimal treatment approach in these patients.
Mouhammad Jumaa (Toledo, United States) reported results of the CLEVER trial: CLEVIDIPINE INFUSION FOR BLOOD PRESSURE MANAGEMENT AFTER SUCCESSFUL REVASCULARIZATION IN ACUTE ISCHEMIC STROKE (CLEVER).
Several trials made a recommendation of SBP <140 mmHg after successful recanalization of anterior LVO-stroke. In this randomized trial using clevidipine, patients were randomized to an intensive blood pressure management group (90-120 mmHg) versus a standard BP management group (90-160 mmHg). The rates of excellent outcome (mRS 0-1), favorable functional outcome (mRS 0-2) and rates of sICH were not different between the treatment arms. In conclusion, clevidipine is safe and effective when used for blood pressure control after mechanical thrombectomy. Intensive SBP control with a cap of 120 mmHg did not reduce the rate of hemorrhagic transformation or sICH and resulted in a numerically lower rate of favorable functional outcome, albeit not showing a significant difference.
Götz Thomalla (Hamburg, Germany) presented FUNCTIONAL OUTCOME AND QUALITY OF LIFE AT 12 MONTHS AFTER THROMBECTOMY FOR STROKE WITH EXTENDED LESION IN THE TENSION TRIAL. These are extended results of the TENSION trial which demonstrated improved functional outcomes in patients treated with EVT and large infarcts (ASPECTS <6). Functional outcome at 12 months showed a significant treatment effect in median mRS scores, higher rates of favorable functional outcomes (mRS 0-2) and in preventing disability (mRS 0-3). Also, quality of life was better in the EVT group after 1 year. In conclusion, using EVT in patients with established large infarcts (ASPECTS <6), the intervention showed a reduction of mortality and dependency after 1 year and a reduced mortality during the first 12 months of follow-up. Götz concluded that in patients with acute ischemic stroke and LVO with established large infarct, thrombectomy results in better functional outcome, better quality of life and lower mortality at 12 months compared to medical treatment alone. After one year, thrombectomy was associated with a 17% absolute increase of patients able to walk unaided. Thrombectomy is associated with long-term improvement of survival of patients with large infarct with a relative mortality-reduction of 30%.
In my opinion, these results seem reassuring when physicians are in doubt to treat these severely affected patients and provide a quantitative basis for prognostic estimation, and Götz Thomalla pointed out that a reasonable number of patients (17%) further improved after 3 months until 12 months after the event.
Edo Richard from Nijmegen, Netherlands was the last speaker of this session and presented results of the PREVENTION OF DEMENTIA USING MOBILE PHONE APPLICATIONS (PRODEMOS) trial. The PRODEMOS trial assessed the efficacy of an app with an individual coach compared to a static app alone in changing the CAIDE dementia risk score including total cholesterol, systolic BP, BMI and physical activity. Patients with pre-stroke dementia and cognitive impairment were excluded from the trial. The coach-supported mHEALTH intervention for risk reduction was feasible to implement and the implementation in the low socioeconomic status population was possible, but challenging. The effects on improvement of risk factor control were small and significantly improved physical activity and smoking cessation. The clinical relevance of these findings is yet to be determined.
This second large clinical trial session brought very exciting results and made the thousands of spectators hungry for more in the next large clinical trial session later this morning.
