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Within the last year, four randomised-controlled clinical trials (RCTs) have been published comparing intravenous thrombolysis (IVT) with tenecteplase and alteplase in acute ischaemic stroke (AIS) patients with a non-inferiority design for three of them. An expedited recommendation process was initiated by the European Stroke Organisation (ESO) and conducted according to ESO standard operating procedure based on the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) framework. We identified three relevant Population, Intervention, Comparator, Outcome (PICO) questions, performed systematic reviews of the literature and meta-analyses, assessed the quality of the available evidence, and wrote evidence-based recommendations. Expert consensus statements were provided if insufficient evidence was available to provide recommendations based on the GRADE approach. For patients with AIS of

Background: Monitoring and measuring different aspects of stroke care pathway is the cornerstone for improvement of quality. We aim to analyze and give an overview of improvements of stroke care quality in Estonia. Patients and methods: National stroke care quality indicators are collected and reported using reimbursement data and include all adult stroke cases. In Estonia, five stroke-ready hospitals are participating in Registry of Stroke Care Quality (RES-Q), providing data on all stroke patients 1 month every year. Data from the national quality indicators and RES-Q from 2015 to 2021 are presented. Results: The proportion of intravenous thrombolysis for all Estonian hospitalized ischemic stroke cases increased from 16% (95% Confidence Interval, CI 15%–18%) in 2015 to 28% (95% CI 27%–30%) in 2021. Mechanical thrombectomy was provided to 9% (95% CI 8%–10%) in 2021. The 30-day mortality rate has decreased from 21% (95% CI 20%–23%) to 19% (95% CI 18%–20%). More than 90% of patients with cardioembolic stroke are prescribed anticoagulants at discharge, but only 50% are on anticoagulant treatment 1 year after stroke. Also, the availability of inpatient rehabilitation needs improvement, being 21% (95% CI 20%–23%) in 2021. A total of 848 patients are included in the RES-Q. The proportion of patients receiving recanalization therapies was comparable to the national stroke care quality indicators. All stroke-ready hospitals show good onset-to-door times. Conclusion: The overall stroke care quality in Estonia is good, especially the availability of recanalization treatments. However, secondary prevention and the availability of rehabilitation services need improvement in the future.

Background Inflammation contributes to unstable atherosclerotic plaque and stroke. In randomised trials in patients with coronary disease, canukinumab (an interleukin-1B antagonist) and colchicine (a tubulin inhibitor with pleiotropic anti-inflammatory effects) reduced recurrent vascular events. Hypothesis: Anti-inflammatory therapy with low-dose colchicine plus usual care will reduce recurrent vascular events in patients with non-severe, non-cardioembolic stroke and TIA compared with usual care alone. Design CONVINCE is a multi-centre international (in 17 countries) Prospective, Randomised Open-label, Blinded-Endpoint assessment (PROBE) controlled Phase 3 clinical trial in 3154 participants. The intervention is colchicine 0.5 mg/day and usual care versus usual care alone (antiplatelet, lipid-lowering, antihypertensive treatment, lifestyle advice). Included patients are at least 40 years, with non-severe ischaemic stroke (modified Rankin score ≤3) or high-risk TIA (ABCD2 > 3, or positive DWI, or cranio-cervical artery stenosis) within 72 hours-28 days of randomisation, with qualifying stroke/TIA most likely caused by large artery stenosis, lacunar disease, or cryptogenic embolism. Exclusions are stroke/TIA caused by cardio-embolism or other defined cause (e.g. dissection), contra-indication to colchicine (including potential drug interactions), or incapacity for participation in a clinical trial. The anticipated median follow-up will be 36 months. The primary analysis will be by intention-to-treat. Outcome The primary outcome is time to first recurrent ischaemic stroke, myocardial infarction, cardiac arrest, or hospitalisation with unstable angina (non-fatal or fatal). Summary CONVINCE will provide high-quality randomised data on the efficacy and safety of anti-inflammatory therapy with colchicine for secondary prevention after stroke. Schedule First-patient first-visit was December 2016. Recruitment to complete in 2021, follow-up to complete in 2023.

BackgroundThere are limited data on intravenous thrombolysis treatment in ischemic stroke patients with prestroke disability.AimWe aimed to evaluate safety and outcomes of intravenous thrombolysis treatment in stroke patients with prestroke disability.MethodsWe analyzed 88,094 patients treated with intravenous thrombolysis, recorded in the Safe Implementation of Treatments in Stroke (SITS) International Thrombolysis Register between January 2003 and December 2017, with available NIHSS data at stroke-onset and after 24 h. Of them, 4566 patients (5.2%) had prestroke disability, defined as a modified Rankin Scale score of 3–5. Safety outcome measures included Symptomatic Intracerebral Hemorrhage, any type of parenchymal hematoma on 24 h imaging scans irrespective of clinical symptoms, and death within seven days. Early outcome measures were 24-h NIHSS improvement (≥4 from baseline to 24 h).ResultsPatients with prestroke disability were older, had more severe strokes, and more comorbidities than patients without prestroke disability. When comparing patients with prestroke disability with patients without prestroke disability, there was however no significant increase in adjusted odds for symptomatic intracerebral hemorrhage (adjusted odds ratio 0.83 (95% CI 0.60–1.15) (absolute difference in proportion 1.17% vs. 1.27%)) or for parenchymal hemorrhage (adjusted odds ratio 0.96 (0.83–1.11) (7.51% vs. 6.34%)). The prestroke disability group had a significantly lower-adjusted odds ratio for a 24-h NIHSS improvement (adjusted odds ratio 0.79 (0.73–0.85) (45.95% vs. 48.45%)) and a higher adjusted odds ratio for seven-day mortality (aOR 1.40 (1.21–1.61) (10.40% vs. 4.93%)).ConclusionsIntravenous thrombolysis in acute ischemic stroke patients with prestroke disability was not associated with an increased risk of symptomatic intracerebral hemorrhage or parenchymal hemorrhage. Prestroke disability was however associated with a higher risk of early mortality compared to patients without prestroke disability.

Background and aims The aim of the present study was to assess the risk factor burden and stroke etiology of young stroke patients in Estonia and to compare the results with similar cohorts from other countries. Methods This study includes ischemic stroke patients aged 18–54 years from the prospective Estonian Young Stroke Registry between 2013 and 2020. All patients were managed in a stroke unit following a prespecified detailed protocol. Data on stroke risk factors, etiology, and stroke severity were analyzed. Results A total of 437 patients (mean age 44.7 ± 8.3 years; 62% males) were included in the registry during the 8-year study period. A total of 50.2% of patients had ≥ 3 well-documented risk factors (higher for men: odds ratio (OR) 3.8; 95% confidence interval (CI) 1.8–8.3; p < .001) and 6.2% of patients had ≥ 3 less well-documented risk factors. While 42% of patients had undetermined cause of stroke (34% of them cryptogenic), the second most frequent etiologies were large-artery atherosclerosis and cardioembolism (both 19%). 60 percent of cardioembolic strokes were due to high-risk causes. Large-artery atherosclerosis was more prevalent in men (OR 1.8; 95% CI 1–3.3; p = .05) and among older patients (OR 6.2; 95% CI 1.8–21.4; p = .008). The median National Institutes of Health Stroke Scale score on admission was 3 (interquartile ranges 2–6), stroke was more severe in men ( p = .05). Conclusions Our study revealed that young patients with stroke in Estonia have higher burden of well-documented risk factors, higher prevalence of high-risk cardioembolic causes and higher prevalence of large-artery stroke compared to other young stroke cohorts.

The aim of the present European Stroke Organisation guideline document is to provide clinically useful evidence-based recommendation on reversal of anticoagulant activity VKA (warfarin, phenprocoumon and acenocoumarol), direct factor II (thrombin) inhibitors (dabigatran etexilat) and factor-Xa-inhibitors (apixaban, edoxaban and rivaroxaban) in patients with acute intracerebral haemorrhage. The guideline was prepared following the Standard Operational Procedure for a European Stroke Organisation guideline document and according to GRADE methodology. As a basic principle, we defined use of oral anticoagulation pragmatically: oral anticoagulation use is assumed by positive medical history unless relevant anticoagulant activity is regarded unlikely by medical history or has been ruled out by laboratory testing. Overall, we strongly recommend using prothrombin complex over no treatment and fresh-frozen plasma in patients on VKA plus vitamin K. We further strongly recommend using idarucizumab in patients on dabigatran and make a recommendation for andexanet alfa in patients on rivaroxaban and apixaban over no treatment. We make a weak recommendation on using high-dose prothrombin complex concentrate (50 IU/kg) for all patients taking edoxaban and for patients on rivaroxaban or apixaban in case andexanet alfa is not available. We recommend against using tranexamic acid and rFVIIa, outside of trials. The presented treatment recommendations aim to normalise coagulation, there is no or only indirect data on effects on functional outcome or mortality, and only little data from randomised controlled trials.

Background Elderly patients are at high risk of complications after stroke, such as infections and fever. The occurrence of these complications has been associated with an increased risk of death or dependency. Hypothesis: Prevention of aspiration, infections, or fever with metoclopramide, ceftriaxone, paracetamol, or any combination of these in the first four days after stroke onset will improve functional outcome at 90 days in elderly patients with acute stroke. Design International, 3 × 2-factorial, randomised-controlled, open-label clinical trial with blinded outcome assessment (PROBE) in 3800 patients aged 66 years or older with acute ischaemic stroke or intracerebral haemorrhage and an NIHSS score ≥ 6. Patients will be randomly allocated to any combination of oral, rectal, or intravenous metoclopramide (10 mg thrice daily); intravenous ceftriaxone (2000 mg once daily); oral, rectal, or intravenous paracetamol (1000 mg four times daily); or usual care, started within 24 h after symptom onset and continued for four days or until complete recovery or discharge from hospital, if earlier. Outcome: The primary outcome measure is the score on the modified Rankin Scale at 90 days (± 14 days), as analysed with multiple regression. Summary: This trial will provide evidence for a simple, safe and generally available treatment strategy that may reduce the burden of death or disability in patients with stroke at very low costs. Planning: First patient included in May 2016; final follow-up of the last patient by April 2020. Registration: ISRCTN, ISRCTN82217627, https://doi.org/10.1186/ISRCTN82217627

Background Elevated blood pressure following acute stroke is common, and yet early antihypertensive treatment is controversial. ACCESS suggested a beneficial effect of the angiotensin receptor blocker candesartan in the acute phase of stroke, but these findings need to be confirmed in new, large trials. Aims and design The Scandinavian Candesartan Acute Stroke Trial is an international randomised, placebo-controlled, double-blind trial of candesartan in acute stroke. We plan to recruit 2500 patients presenting within 30 h of stroke (ischaemic or haemorrhagic) and with systolic blood pressure >= 140 mmHg. The recruited patients are randomly assigned to candesartan or placebo for 7-days (doses increasing from 4 to 16 mg once daily). Randomisation is performed centrally via a secure web interface. The follow-up period is 6-months. Patients are included from the following nine North-European countries: Norway, Sweden, Denmark, Belgium, Germany, Poland, Lithuania, Estonia and Finland. Study outcomes There are two co-primary effect variables:center dot Functional status at 6-months, measured by the modified Rankin Scale, and center dot vascular death, myocardial infarction or stroke during the first 6-months.Secondary outcome variables:Secondary effect variables include center dot the Barthel index (functional status)center dot EuroQol (quality of life) and center dot Mini-mental state examination (cognition) at 6-months center dot Health economic costs during the first 6-months Funding The Scandinavian Candesartan Acute Stroke Trial receives basic funding from Norwegian health authorities. AstraZeneca supplies the trial drugs, and AstraZeneca and Takeda support the trial with limited, unrestricted grants. Summary The Scandinavian Candesartan Acute Stroke Trial is the first large trial of angiotensin receptor blockers in patients with elevated blood pressure and acute stroke, and aims to answer whether treatment with angiotensin receptor blockers is beneficial for this indication.