Management of Acute Stroke: Past, Present and Future

Abstract Stroke is a leading global cause of death and disability, with a lifetime risk of 1 in 4 individuals. With such substantial socio-economic and personal costs, there is an urgent need for effective treatments to reduce the burden of stroke-related disease. Worldwide, around 1 in 3 strokes are due to haemorrhage into the brain (intracerebral haemorrhage; ICH), while the remainder are due to ischaemia from a blocked artery. Until the 1990s, there were no proven treatments to alter the outcome of stroke and an attitude of therapeutic nihilism was reflected in the prevailing (and inappropriate) term of “cerebrovascular accident.” Indeed, an article in the Postgraduate Medical Journal from 1961 by Shaw 1 noted that “the considerable investment of thought and endeavour in the field of cerebrovascular disease in recent years, has not yet yielded substantial dividend.” Thankfully, since then, we have seen extraordinary advances in effective stroke care. The first proven acute treatments for ischaemic stroke included thrombolysis within 3 h, aspirin to prevent early recurrence, and stroke unit care. Therapies to restore blood flow were based on the concept of the “penumbra” (i.e. potentially salvageable tissue) developed by Lindsay Symon and colleagues 2 working at the Institute of Neurology, Queen Square, London, in the 1980s. Since then, stroke medicine has seen arguably one of the largest positive transformations in its therapeutic landscape of any medical field. Proven interventions to improve outcomes after cerebral ischaemia now include intravenous thrombolysis with tenecteplase or alteplase in an extended time window (using imaging-based selection using computed tomography or magnetic resonance based methods), mechanical thrombectomy (initially within 6 h and subsequently up to 24 h), dual antiplatelet therapy for minor non-cardioembolic ischaemic stroke or transient ischaemic attack, and early oral anticoagulation after ischaemic stroke in patients with atrial fibrillation 3. Revascularisation treatments are most effective when started as early as possible, giving rise to the often-quoted maxim: “time is brain” 4. Mechanical thrombectomy for patients with acute ischaemic stroke due to large vessel occlusion has been perhaps the most transformative of these interventions, with a huge reduction in functional disability (number needed to treat to improve functional outcome ~3) when compared to standard medical care alone. Multiple randomized controlled trials of mechanical thrombectomy show one of the largest treatment effect sizes in medicine 5. The challenge in many healthcare systems is now one of the implementation of this proven treatment intervention. Intracerebral haemorrhage is the most disabling and lethal form of stroke, yet interventions now show promise even for this stroke type. There is now evidence of improved outcome for intracerebral haemorrhage with early and sustained intensive blood pressure lowering 6, and for lobar intracerebral haemorrhage treated with haematoma evacuation using minimally invasive surgery 7. As for ischaemic stroke, emerging evidence also suggests that early intervention is essential to maximise treatment benefit in acute stroke due to intracerebral haemorrhage. There are many exciting areas for future developments in stroke medicine. These include earlier pre-hospital diagnosis using telemedicine, point-of-care biomarkers or even wearable devices, which might allow the commencement of effective treatments for ischaemia or haemorrhage in the ambulance. Antithrombotic and thrombolytic drugs are likely to evolve further, with the aim of improving antithrombotic efficacy while maintaining the lowest possible risk of haemorrhage. Adjunctive therapies to prolong the duration of the ischaemic penumbra or augment reperfusion treatments are under investigation. There is also a need for specific treatments for small vessel occlusion, which may not be due to conventional thrombo-embolism and is not accessible for current thrombectomy devices. In the field of stroke due to intracerebral haemorrhage, it is likely that the optimal technique, time window and patient population for effective minimally invasive surgery will all be refined further. In conclusion, stroke is a common and important global healthcare challenge for which we have seen enormous advances in the last few decades. Prospects are also bright for further advances in the coming years. References 1. Shaw DA. The diagnosis and treatment of cerebrovascular disease. Postgrad Medical J 1961; 37: 412–422. 2. Astrup J. The Ischemic Penumbra 50 Years: A Personal Vignette. Stroke 2025;56:3321–5. 3. Dehbi H-M, Fischer U, Åsberg S, et al. Collaboration on the optimal timing of anticoagulation after ischaemic stroke and atrial fibrillation: a systematic review and prospective individual participant data meta-analysis of randomised controlled trials (CATALYST). Lancet 2025;406:43–51. 4. Emberson J, Lees KR, Lyden P, et al. Effect of treatment delay, age, and stroke severity on the effects of intravenous thrombolysis with alteplase for acute ischaemic stroke: a meta-analysis of individual patient data from randomised trials. Lancet 2014;384:1929–35. 5. Goyal M, Menon BK, van Zwam WH, et al. Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials. Lancet 2016;387:1723–31. 6. Wang X, Ren X, Li Q, et al. Effects of blood pressure lowering in relation to time in acute intracerebral haemorrhage: a pooled analysis of the four INTERACT trials. Lancet Neurol 2025;24:571–9. 7. Pradilla G, Ratcliff JJ, Hall AJ, et al. Trial of Early Minimally Invasive Removal of Intracerebral Hemorrhage. N Engl J Med 2024;390:1277–89.