The European Stroke Organisation Conference (ESOC) has become a major feature in the stroke calendar since its inception in 2015. This year, thousands of stroke researchers and clinicians from around the world assembled in Munich to catch breaking results of large clinical trials, and attend educational workshops and expert debates on current controversies. In this article I summarise some of the research from the 3-day conference I found most interesting.
Rapid pre-hospital recognition of stroke and triage to specialist centres is fundamental to effective therapy. Researchers from Copenhagen University Hospital have contributed to this landscape with an artificial intelligence (AI) framework to improve the recognition of acute stroke by emergency call handlers. Using a dataset of 1.5 million emergency calls they trained the model to predict the risk of stroke from transcribed text of the conversation. On validating the model, they showed it performed more effectively than human emergency call handlers; with a sensitivity of 63% vs 53% and a positive predictive value of 25% vs 17% . This is an exciting and novel use for AI, but further work is needed to show improved clinical outcomes and cost efficacy. Potential future developments of the model include direct interpretation of the audio and use of non-audio features, such as dysarthria.
Remote ischaemic conditioning (RIC) is a concept that has been around since at least the 1990’s. It involves inducing cycles of focal ischaemia followed by reperfusion, usually by means of a blood pressure cuff, the theory being to protect from more severe ischaemia in a distant organ. Researchers at Aarhus University Hospital reported the findings of their trial of 1,500 suspected stroke patients who were randomised to receive RIC or sham in a pre-hospital setting . Although there were no safety issues, it failed to achieve the primary outcome of improved function at 90 days, or any of the secondary endpoints. For now at least, RIC remains an interesting concept.
Results from the much anticipated Early versus Late Anticoagulation for Stroke with Atrial Fibrillation (ELAN) trial had the greatest implications for clinical practice. An international collaboration, coordinated by Professor Urs Fischer at the University of Basel, randomised 2,013 patients with cardioembolic stroke to receive anticoagulation either within 48 hours or on day 3-4 for those with minor or moderate sized infarcts, and on day 6-7 or on day 12-14 for those with major stroke, as determined by pre-specified infarct sizes. There were no statistically significant differences in outcomes between the groups, and the authors estimated the incidence of recurrent ischaemic stroke, systemic embolism, major extracranial bleeding, symptomatic intracranial haemorrhage, or vascular death at 30 days lay between 2.8% lower and 0.5% higher with early compared to late use of direct oral anticoagulants (DOAC) . Several similar trials are underway to confirm these results, but stroke clinicians should have increased confidence to anticoagulate patients earlier than current clinical practice.
Building on the theme of increasing confidence in the safety of DOACs, an international collaboration, lead by the Karolinska Institutet, reported on the safety of intravenous thrombolysis in patients receiving DOAC therapy. In their retrospective analysis of more than 700 patients from the SITS-international registry, there were no significant differences between patients receiving and not receiving DOAC therapy in functional outcome or intracranial haemorrhage following intravenous thrombolysis . Although observational, these data support others , and are a valuable contribution to an area that is not favourable for randomised controlled trials.
In contrast to the improvement in ischaemic stroke mortality rates, intracerebral haemorrhage (ICH) remains a devastating condition with few therapeutic options [6,7]. Mercifully however, two randomised trials presented at ESOC this year propose interventions with effect sizes comparable to those for ischaemic stroke, offering some much needed hope in this field.
Although surgical haematoma evacuation has long been an attractive proposition, previous trials have not proven benefit over conservative management [8,9]. Building on the knowledge gained from this work, particularly with regards to patient selection and surgical technique, US-based investigators compared hyperacute (within 24 hours) minimally invasive parafascicular surgery with conservative management in more than 300 patients with spontaneous supratentorial ICH. The median reduction in haematoma volume with surgery was 35ml (88%) and significantly reduced 30-day mortality, 6-month function and overall length of hospital stay, compared to conservative management .
Regrettably, patients with ICH are often met with therapeutic nihilism and experience a lower threshold for withdrawal of active management . Results of the third Intensive Care Bundle with Blood Pressure Reduction in Acute Cerebral Haemorrhage Trial (INTERACT3) challenged this by proving the benefit of an ICH-specific care bundle in more than 7,000 patients, principally from low- and middle-income countries. Compared to local ‘standard care’, the bundle, comprising early intensive lowering of blood pressure and management of various abnormal physiological parameters, had a number needed to treat of 35 for improved functional outcome and reduced mortality at 6 months .
Anticoagulation of patients with embolic stroke of undetermined source (ESUS) remains controversial. The concept of atrial cardiopathy to select a subpopulation who may benefit from anticoagulation is not new, but the AtRial Cardiopathy and Antithrombotic Drugs in Prevention After Cryptogenic Stroke (ARCADIA) trial was the latest attempt at offering these patients more tailored secondary prevention. The trial defined atrial cardiopathy as one of enlarged atrial diameter, elevated serum NT-proBNP level or prolonged P-wave terminal force on ECG. The investigators randomised over 1,000 patients to receive apixaban or aspirin and followed them for an average of 1.8 years. Unfortunately, there was no significant benefit of anticoagulation in reducing recurrent ischaemic stroke or systemic embolism . Of note, the majority of patients were included on the basis of serum and ECG biomarkers, rather than echocardiogram parameters (less than 2% of patients), suggesting future studies are required to better define this at-risk subpopulation.
Finally, cerebral small vessel disease is poorly understood, yet highly prevalent, and has diverse clinical manifestations without specific secondary prevention strategies. Endothelial dysfunction leading to breakdown of the blood-brain barrier is proposed as an important mediating mechanism . The Lacunar Intervention Trial-2 (LACI-2) investigated the feasibility and tolerability of endothelial stabilisation with cilostazol and isosorbide mononitrate in 363 lacunar stroke patients. The trial demonstrated its primary aim, paving the way for a larger study, but also tantalisingly showed that the combination of drugs reduced recurrent stroke, dependence, and cognitive impairment during 12 month follow-up . These findings need to be confirmed in a future adequately-powered trial, but reveal a glimmer of hope for a better understanding and some therapeutic options for this common and devastating condition.
- Havtorn J.D, et al. A retrospective study on deep learning- enabled stroke recognition for a medical help line. Presented at the European Stroke Organisation Conference; 24 May 2023; Munich, Germany.
- Blauenfeldt R, et al. Remote ischemic conditioning in patients with acute stroke: a multicentre, randomised, patient-assessor blinded, sham-controlled study (RESIST). Presented at the European Stroke Organisation Conference; 24 May 2023; Munich, Germany.
- Fischer U, et al. Early versus late anticoagulation for stroke with atrial fibrillation (ELAN). Presented at the European Stroke Organisation Conference; 24 May 2023; Munich, Germany.
- Saflund M, et al. IV thrombolysis in patients taking direct oral anticoagulation treatment prior to stroke onset: results from SITS-INTERNATIONAL stroke registry. Presented at the European Stroke Organisation Conference; 24 May 2023; Munich, Germany.
- Meinel T, et al. Intravenous thrombolysis in patients with ischaemic stroke and recent ingestion of direct oral anticoagulants. JAMA Neurology. 2023; 80(3):233-243. https://doi.org/10.1001/jamaneurol.2022.4782
- Krishnamurthi RV, et al. Global, regional and country-specific burden of ischaemic stroke, intracerebral haemorrhage and subarachnoid haemorrhage: a systematic analysis of the global burden of disease study 2017. Neuroepidemiology. 2020;54:171-9. https://doi.org/10.1159/000506396
- Poon MT, et al. Long-term prognosis after intracerebral haemorrhage: systematic review and meta-analysis. J Neurol Neurosurg Psychiatry. 2014;85:660-667. https://doi.org/10.1136/jnnp-2013-306476
- Mendelow AD, et al. Early surgery versus initial conservative treatment in patients with spontaneous supratentorial intracerebral haematomas in the International Surgical Trial in Intracerebral Haemorrhage (STICH): a randomised trial. Lancet. 2005;365:387-397. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(05)17826-X/fulltext
- Mendelow AD, et al. Early surgery versus initial conservative treatment in patients with spontaneous supratentorial lobar intracerebral haematomas (STICH II): a randomised trial. Lancet. 2013;382:397-408. https://doi.org/10.1016/S0140-6736(13)60986-1
- Hall A. Early minimally-invasive removal of intracerebral haemorrhage (ENRICH). Presented at: ESOC 2023. May 25, 2023. Munich, Germany.
- Morgenstern LB, et al. Full medical support for intracerebral haemorrhage. Neurology. 2015;84:1739-1744. https://doi.org/10.1212/WNL.0000000000001525
- Ma L, et al. The third Intensive Care Bundle with Blood Pressure Reduction in Acute Cerebral Haemorrhage Trial (INTERACT3): an international, stepped wedge cluster randomised controlled trial. Lancet. 2023. Online ahead of print.
- Kamel H. Primary results of the atrial cardiopathy and antithrombotic drugs in prevention after cryptogenic stroke (ARCADIA) randomized trial. Presented at: ESOC 2023. May 24, 2023. Munich, Germany.
- Quick S, et al. A vessel for change: Endothelial dysfunction in cerebral small vessel disease. Trends in Neuroscience. 2021;44:289-305. https://doi.org/10.1016/j.tins.2020.11.003
- Wardlaw J. Isosorbide Mononitrate and Cilostazol Treatment in Patients With Symptomatic Cerebral Small Vessel Disease: The Lacunar Intervention Trial-2 (LACI-2) Randomized Clinical Trial. JAMA Neurology. 2023. Online ahead of print.