The latest scientific findings on strokes were once again the focus of Europe’s largest stroke conference. As the world’s leading forum for advances in research and clinical care of patients with cerebrovascular disease, a packed, high-caliber scientific program was presented. Including important clinical trials, cutting-edge seminars, educational workshops, scientific communications, the latest research and debates, and current controversies.
A multicenter, prospective, randomized, sham-controlled trial evaluated the efficacy of remote ischemic conditioning ( RIC) to improve functional outcome at 90 days in patients with acute stroke [1]. A total of 1500 patients with suspected acute stroke were admitted. Patients were randomly assigned to RIC or sham treatment, which was started in the outpatient clinic and continued during hospitalization. Half of the patients were enrolled in the study within the first hour of symptom onset. After exclusion of 149 (10%) patients with transient ischemic attack and 382 (27%) patients with stroke mimic, the target population consisted of 902 patients (436 with RIC and 466 with sham treatment) with a confirmed diagnosis of ischemic or hemorrhagic stroke. Treatment with RIC was not associated with improvement in functional outcomes at 90 days, which was the primary endpoint of the study. RIC was not superior to sham treatment on other important secondary end points. Accordingly, the results failed to demonstrate the efficacy of early conditioning in acute stroke.
Prevention of the risk of complications
Infections and fever often occur after a stroke, especially in elderly patients. These complications are associated with an increased risk of mortality and poor functional outcome. Whether preventive treatment with antibiotics or antipyretic agents can improve functional outcome in patients with acute stroke has been the subject of previous studies-including three large randomized clinical trials. In these studies, preventive treatment with antibiotics or antipyretic agents did not improve functional outcomes. But the studies were conducted in broad populations that included patients at low risk for complications after stroke, reducing the potential for benefit from these measures.
The current study is an international, multicenter, 3 × 2 factorial, randomized, controlled, open-label clinical trial with blinded outcome assessment [2]. Patients aged 66 years or older with moderate-to-severe ischemic stroke or intracerebral hemorrhage were eligible for the study. Whether prevention of infection or fever with metoclopramide, ceftriaxone, acetaminophen, or a combination of these agents in the first four days after stroke onset improves functional outcome at 90 days was studied. From April 2016 to June 2022, 1493 patients were enrolled from 67 European centers. After excluding patients who withdrew consent or lost to follow-up, 1471 patients were included in the intention-to-treat analysis. It was found that preventive use of the above medications did not reduce the risk of poor functional outcome at 90 days. Accordingly, the results do not support the preventive use of antiemetics, antipyretics, or medications in elderly patients with acute stroke.
Early use of oral anticoagulation
About 80% of all strokes are caused by blockage of an artery in the brain. Up to 20% of these strokes are caused by blood clots that form in the heart in people with atrial fibrillation. Blood thinners called direct oral anticoagulants (DOACs) are used to prevent blood clots in people with atrial fibrillation. However, it is unclear how early after a stroke therapy should be started. There is a potentially increased risk of bleeding, which may be highest in the first few days. is highest in the first few days. However, the potential benefit of these drugs is also greatest in these early days. A new international clinical study has addressed this controversy [3].
The study shows that early treatment is less likely to result in a recurrence than later onset – without increasing the risk of complications. The study included 2013 participants with acute ischemic stroke and atrial fibrillation from 103 different stroke units in 15 different countries. Based on the size and location of the infarct on imaging (ie, a mild, moderate, or severe stroke), participants were randomly assigned to early treatment initiation or later guideline-recommended treatment initiation. Early onset was defined as within 48 hours of a mild/moderate stroke or on day 6-7 after a severe stroke. Late onset was defined as day 3-4 after a mild stroke, day 6-7 after a moderate stroke, or day 12-14 after a severe stroke. The primary end point was a composite of recurrent ischemic stroke, symptomatic intracranial hemorrhage, extracranial hemorrhage, systemic embolism, or vascular death within 30 days of randomization. At 30 days, the primary outcome occurred in 2.9% in the early treatment group and 4.1% in the late treatment group. After 90 days, the difference in the rate of the composite outcome was -1.9%. Recurrence of ischemic stroke at 30 days occurred in 14 participants (1.4%) in the early-treatment group and in 25 participants (2.5%) in the late-treatment group. The study also suggests that the incidence of symptomatic intracerebral hemorrhage with early anticoagulation is low when imaging-based classification is used.
Is effective blood pressure management individualized?
The optimal strategy for blood pressure management in endovascular treatment of cerebral stroke is not known. Therefore, a prospective, randomized, open-label, blinded endpoint study investigated whether individualized blood pressure treatment demonstrated more favorable functional outcomes compared with standard blood pressure treatment [4]. Patients with anterior circulation stroke and a National Institutes of Health Stroke Scale ( NIHSS ) score of 8 or higher were included. The primary end point of favorable functional outcome was defined as a modified Rankin score of 0 to 2 at 90 days. Secondary end points included mortality, short-term outcome as measured by NIHSS score, and safety measures such as critical hypo- or hypertension, cerebral hemorrhage, and use of vasopressors or vasodepressors.
During the study period, 123 patients were treated with individualized blood pressure management and 127 with standard blood pressure management. The rate of favorable functional outcomes at 3 months was not significantly different between the individualized and standard blood pressure treatment groups (25% versus 24%).
Operate intracerebral hemorrhage
In contrast to ischemic stroke, there are few acute treatment options with proven benefit for patients with spontaneous supratentorial intracerebral hemorrhage (ICH). Current guidelines recommend standard medical treatment consisting of admission to a stroke unit, reversal of the clotting disorder, and control of blood pressure. Several large clinical trials have investigated the effect of surgical treatment, including craniotomy and minimally invasive surgery, but have failed to show a positive effect on functional outcome. In part, this can be explained by the long time lag between the onset of symptoms and the start of surgery and the disadvantages associated with standard craniotomy. Given this disagreement about the role of surgical intervention in supratentorial ICH, several new studies have been conducted to compare minimally invasive removal of ICH clots with standard medical treatment in different time windows.
The ENRICH trial compared drug treatment with minimally invasive trans-sulcal parafascicular surgical (MIPS) ICH clot removal using the BrainPath® and Myriad® devices, initiated within 24 hours of symptom onset [5]. The study was an adaptive Bayesian design that allowed enrichment of a prespecified ICH population (anterior basal ganglia [ABG] vs. lobar). The primary outcome was a functional outcome at six months. Patients were randomized into blocks according to the site of ICH (ABG or lobar) and Glasgow Coma Scale (GCS). After enrollment of 175 patients, the population was enriched to focus only on the lobar population. A total of 300 patients from 37 centers in the United States were randomly assigned to early MIPS-ICH clot evacuation or medical treatment, with 286 patients receiving complete follow-up. Of the patients randomized to clot removal (150), the primary Bayesian analysis compared the mean UWmRS score at 6 months between treatment groups, with an estimated mean UWmRS score of 0.374 for the MM group and 0.458 for the MIPS group, a difference of 0.084. The Bayesian posterior probability for superiority of the intervention was 0.9813, which is above the prespecified threshold of 0.975 for superiority of MIPS over MM. The overall benefit of MIPS appears to be due to the strong positive effect observed in participants with lobar ICH. This is the first study to demonstrate a functional benefit of surgical clot removal in patients with supratentorial ICH.
Congress:9th European Stroke Organisation Conference (ESOC)
Literature:
- 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.
- de Jonge J, et al: Prevention of complications to improve outcome in elderly patients with acute stroke (PRECIOUS): A randomised, open, phase III, clinical trial with blinded outcome assessment. Presented at the European Stroke Organisation Conference; 24 May 2023; Munich, Germany.
- Fischer U, Dawson J, et al: Early vs late anticoagulation in stroke patients with atrial fibrillation. Presented at the European Stroke Organisation Conference; 24 May 2023; Munich, Germany.
- Schönenberger S, et al.: Effect of individualised versus standard blood pressure management during endovascular stroke treatment under procedural sedation (INDIVIDUATE) on clinical outcome. Presented at the European Stroke Organisation Conference; 26 May 2023; Munich, Germany.
- Hall A, et al: Very early minimally invasive removal of intracerebral hemorrhage: the ENIRCH trial. Presented at the European Stroke Organisation Conference; 25 May 2023; Munich, Germany.
InFo NEUROLOGY & PSYCHIATRY 2023; 21(4): 20-21 (published 8/18-23, ahead of print).
