Tranexamic acid can prevent death due to bleeding after trauma and post-partum haemorrhage. We aimed to assess whether tranexamic acid reduces haematoma expansion and improves outcome in adults with stroke due to intracerebral haemorrhage. We did an international, randomised placebo-controlled trial in adults with intracerebral haemorrhage from acute stroke units at 124 hospital sites in 12 countries. Participants were randomly assigned (1:1) to receive 1 g intravenous tranexamic acid bolus followed by an 8 h infusion of 1 g tranexamic acid or a matching placebo, within 8 h of symptom onset. Randomisation was done centrally in real time via a secure website, with stratification by country and minimisation on key prognostic factors. Treatment allocation was concealed from patients, outcome assessors, and all other health-care workers involved in the trial. The primary outcome was functional status at day 90, measured by shift in the modified Rankin Scale, using ordinal logistic regression with adjustment for stratification and minimisation criteria. All analyses were done on an intention-to-treat basis. This trial is registered with the ISRCTN registry, number ISRCTN93732214. We recruited 2325 participants between March 1, 2013, and Sept 30, 2017. 1161 patients received tranexamic acid and 1164 received placebo; the treatment groups were well balanced at baseline. The primary outcome was assessed for 2307 (99%) participants. The primary outcome, functional status at day 90, did not differ significantly between the groups (adjusted odds ratio [aOR] 0·88, 95% CI 0·76-1·03, p=0·11). Although there were fewer deaths by day 7 in the tranexamic acid group (101 [9%] deaths in the tranexamic acid group vs 123 [11%] deaths in the placebo group; aOR 0·73, 0·53-0·99, p=0·0406), there was no difference in case fatality at 90 days (250 [22%] vs 249 [21%]; adjusted hazard ratio 0·92, 95% CI 0·77-1·10, p=0·37). Fewer patients had serious adverse events after tranexamic acid than after placebo by days 2 (379 [33%] patients vs 417 [36%] patients), 7 (456 [39%] vs 497 [43%]), and 90 (521 [45%] vs 556 [48%]). Functional status 90 days after intracerebral haemorrhage did not differ significantly between patients who received tranexamic acid and those who received placebo, despite a reduction in early deaths and serious adverse events. Larger randomised trials are needed to confirm or refute a clinically significant treatment effect. National Institute of Health Research Health Technology Assessment Programme and Swiss Heart Foundation.

Introduction: Spontaneous non-traumatic intracerebral hemorrhage (ICH) is most often caused by small vessel diseases: deep perforator arteriopathy (hypertensive arteriopathy) or cerebral amyloid angiopathy (CAA). Although ICH accounts for only 10–15% of all strokes it causes a high proportion of stroke mortality and morbidity, with few proven effective acute or preventive treatments. Areas covered: We conducted a literature search on etiology, diagnosis, treatment, management and current clinical trials in ICH. In this review, We describe the causes, diagnosis (including new brain imaging biomarkers), classification, pathophysiological understanding, treatment (medical and surgical), and secondary prevention of ICH. Expert opinion: In recent years, significant advances have been made in deciphering causes, understanding pathophysiology, and improving acute treatment and prevention of ICH. However, the clinical outcome remains poor and many challenges remain. Acute interventions delivered rapidly (including medical therapies – targeting hematoma expansion, hemoglobin toxicity, inflammation, edema, anticoagulant reversal – and minimally invasive surgery) are likely to improve acute outcomes. Improved classification of the underlying arteriopathies (from neuroimaging and genetic studies) and prognosis should allow tailored prevention strategies (including sustained blood pressure control and optimized antithrombotic therapy) to further improve longer-term outcome in this devastating disease.

Objective: It is not known whether patients with atrial fibrillation (AF) with ischemic stroke despite oral anticoagulant therapy are at increased risk for further recurrent strokes or how ongoing secondary prevention should be managed.Methods: We conducted an individual patient data pooled analysis of 7 prospective cohort studies that recruited patients with AF and recent cerebral ischemia. We compared patients taking oral anticoagulants (vitamin K antagonists [VKA] or direct oral anticoagulants [DOAC]) prior to index event (OAC_prior) with those without prior oral anticoagulation (OAC_naive). We further compared those who changed the type (ie, from VKA or DOAC, vice versa, or DOAC to DOAC) of anticoagulation (OAC_changed) with those who continued the same anticoagulation as secondary prevention (OAC_unchanged). Time to recurrent acute ischemic stroke (AIS) was analyzed using multivariate competing risk Fine–Gray models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs).Results: We included 5,413 patients (median age = 78 years [interquartile range (IQR) = 71–84 years]; 5,136 [96.7%] had ischemic stroke as the index event, median National Institutes of Health Stroke Scale on admission = 6 [IQR = 2–12]). The median CHA₂DS₂‐Vasc score (congestive heart failure, hypertension, age≥ 75 years, diabetes mellitus, stroke/transient ischemic attack, vascular disease, age 65–74 years, sex category) was 5 (IQR = 4–6) and was similar for OAC_prior (n = 1,195) and OAC_naive (n = 4,119, p = 0.103). During 6,128 patient‐years of follow‐up, 289 patients had AIS (4.7% per year, 95% CI = 4.2–5.3%). OAC_prior was associated with an increased risk of AIS (HR = 1.6, 95% CI = 1.2–2.3, p = 0.005). OAC_changed (n = 307) was not associated with decreased risk of AIS (HR = 1.2, 95% CI = 0.7–2.1, p = 0.415) compared with OAC_unchanged (n = 585).Interpretation: Patients with AF who have an ischemic stroke despite previous oral anticoagulation are at a higher risk for recurrent ischemic stroke despite a CHA₂DS₂‐Vasc score similar to those without prior oral anticoagulation. Better prevention strategies are needed for this high‐risk patient group. ANN NEUROL 2020;87:677–687

Cerebral microbleeds are a neuroimaging biomarker of stroke risk. A crucial clinical question is whether cerebral microbleeds indicate patients with recent ischaemic stroke or transient ischaemic attack in whom the rate of future intracranial haemorrhage is likely to exceed that of recurrent ischaemic stroke when treated with antithrombotic drugs. We therefore aimed to establish whether a large burden of cerebral microbleeds or particular anatomical patterns of cerebral microbleeds can identify ischaemic stroke or transient ischaemic attack patients at higher absolute risk of intracranial haemorrhage than ischaemic stroke. We did a pooled analysis of individual patient data from cohort studies in adults with recent ischaemic stroke or transient ischaemic attack. Cohorts were eligible for inclusion if they prospectively recruited adult participants with ischaemic stroke or transient ischaemic attack; included at least 50 participants; collected data on stroke events over at least 3 months follow-up; used an appropriate MRI sequence that is sensitive to magnetic susceptibility; and documented the number and anatomical distribution of cerebral microbleeds reliably using consensus criteria and validated scales. Our prespecified primary outcomes were a composite of any symptomatic intracranial haemorrhage or ischaemic stroke, symptomatic intracranial haemorrhage, and symptomatic ischaemic stroke. We registered this study with the PROSPERO international prospective register of systematic reviews, number CRD42016036602. Between Jan 1, 1996, and Dec 1, 2018, we identified 344 studies. After exclusions for ineligibility or declined requests for inclusion, 20 322 patients from 38 cohorts (over 35 225 patient-years of follow-up; median 1·34 years [IQR 0·19-2·44]) were included in our analyses. The adjusted hazard ratio [aHR] comparing patients with cerebral microbleeds to those without was 1·35 (95% CI 1·20-1·50) for the composite outcome of intracranial haemorrhage and ischaemic stroke; 2·45 (1·82-3·29) for intracranial haemorrhage and 1·23 (1·08-1·40) for ischaemic stroke. The aHR increased with increasing cerebral microbleed burden for intracranial haemorrhage but this effect was less marked for ischaemic stroke (for five or more cerebral microbleeds, aHR 4·55 [95% CI 3·08-6·72] for intracranial haemorrhage vs 1·47 [1·19-1·80] for ischaemic stroke; for ten or more cerebral microbleeds, aHR 5·52 [3·36-9·05] vs 1·43 [1·07-1·91]; and for ≥20 cerebral microbleeds, aHR 8·61 [4·69-15·81] vs 1·86 [1·23-1·82]). However, irrespective of cerebral microbleed anatomical distribution or burden, the rate of ischaemic stroke exceeded that of intracranial haemorrhage (for ten or more cerebral microbleeds, 64 ischaemic strokes [95% CI 48-84] per 1000 patient-years vs 27 intracranial haemorrhages [17-41] per 1000 patient-years; and for ≥20 cerebral microbleeds, 73 ischaemic strokes [46-108] per 1000 patient-years vs 39 intracranial haemorrhages [21-67] per 1000 patient-years). In patients with recent ischaemic stroke or transient ischaemic attack, cerebral microbleeds are associated with a greater relative hazard (aHR) for subsequent intracranial haemorrhage than for ischaemic stroke, but the absolute risk of ischaemic stroke is higher than that of intracranial haemorrhage, regardless of cerebral microbleed presence, antomical distribution, or burden. British Heart Foundation and UK Stroke Association.

Background: A small randomized controlled trial suggested that dabigatran may be as effective as warfarin in the treatment of cerebral venous thrombosis (CVT). We aimed to compare direct oral anticoagulants (DOACs) to warfarin in a real-world CVT cohort. Methods: This multicenter international retrospective study (United States, Europe, New Zealand) included consecutive patients with CVT treated with oral anticoagulation from January 2015 to December 2020. We abstracted demographics and CVT risk factors, hypercoagulable labs, baseline imaging data, and clinical and radiological outcomes from medical records. We used adjusted inverse probability of treatment weighted Cox-regression models to compare recurrent cerebral or systemic venous thrombosis, death, and major hemorrhage in patients treated with warfarin versus DOACs. We performed adjusted inverse probability of treatment weighted logistic regression to compare recanalization rates on follow-up imaging across the 2 treatments groups. Results: Among 1025 CVT patients across 27 centers, 845 patients met our inclusion criteria. Mean age was 44.8 years, 64.7% were women; 33.0% received DOAC only, 51.8% received warfarin only, and 15.1% received both treatments at different times. During a median follow-up of 345 (interquartile range, 140–720) days, there were 5.68 recurrent venous thrombosis, 3.77 major hemorrhages, and 1.84 deaths per 100 patient-years. Among 525 patients who met recanalization analysis inclusion criteria, 36.6% had complete, 48.2% had partial, and 15.2% had no recanalization. When compared with warfarin, DOAC treatment was associated with similar risk of recurrent venous thrombosis (aHR, 0.94 [95% CI, 0.51–1.73]; P =0.84), death (aHR, 0.78 [95% CI, 0.22–2.76]; P =0.70), and rate of partial/complete recanalization (aOR, 0.92 [95% CI, 0.48–1.73]; P =0.79), but a lower risk of major hemorrhage (aHR, 0.35 [95% CI, 0.15–0.82]; P =0.02). Conclusions: In patients with CVT, treatment with DOACs was associated with similar clinical and radiographic outcomes and favorable safety profile when compared with warfarin treatment. Our findings need confirmation by large prospective or randomized studies.