Background and Objectives The ULTRA trial showed that ultra-early and short-term tranexamic acid treatment after subarachnoid hemorrhage did not improve clinical outcome at 6 months. An expected... Show moreBackground and Objectives The ULTRA trial showed that ultra-early and short-term tranexamic acid treatment after subarachnoid hemorrhage did not improve clinical outcome at 6 months. An expected proportion of the included patients experienced nonaneurysmal subarachnoid hemorrhage. In this post hoc study, we will investigate whether ultra-early and short-term tranexamic acid treatment in patients with aneurysmal subarachnoid hemorrhage improves clinical outcome at 6 months.Methods The ULTRA trial is a multicenter, prospective, randomized, controlled, open-label trial with blinded outcome assessment, conducted between July 24, 2013, and January 20, 2020. After confirmation of subarachnoid hemorrhage on noncontrast CT, patients were allocated to either ultra-early and short-term tranexamic acid treatment with usual care or usual care only. In this post hoc analysis, we included all ULTRA participants with a confirmed aneurysm on CT angiography and/or digital subtraction angiography. The primary endpoint was clinical outcome at 6 months, assessed by the modified Rankin scale (mRS), dichotomized into good (0-3) and poor (4-6) outcomes.Results Of the 813 ULTRA trial patients who experienced an aneurysmal subarachnoid hemorrhage, 409 (50%) were assigned to the tranexamic acid group and 404 (50%) to the control group. In the intention-to-treat analysis, 233 of 405 (58%) patients in the tranexamic acid group and 238 of 399 (60%) patients in the control group had a good clinical outcome (adjusted odds ratio [aOR] 0.92; 95% CI 0.69-1.24). None of the secondary outcomes showed significant differences between the treatment groups: excellent clinical outcome (mRS 0-2) (aOR 0.76; 95% CI 0.57-1.03), all-cause mortality at 30 days (aOR 0.91; 95% CI 0.65-1.28), and all-cause mortality at 6 months (aOR 1.10; 95% CI 0.80-1.52).Discussion Ultra-early and short-term tranexamic acid treatment did not improve clinical outcomes at 6 months in patients with aneurysmal subarachnoid hemorrhage and therefore cannot be recommended.Classification of Evidence This study provides Class II evidence that tranexamic acid does not improve outcomes in patients presenting with aneurysmal subarachnoid hemorrhage. Show less
Background and Purpose: The frequency of ischemic stroke in patients with coronavirus disease 2019 (COVID-19) varies in the current literature, and risk factors are unknown. We assessed the... Show moreBackground and Purpose: The frequency of ischemic stroke in patients with coronavirus disease 2019 (COVID-19) varies in the current literature, and risk factors are unknown. We assessed the incidence, risk factors, and outcomes of acute ischemic stroke in hospitalized patients with COVID-19. Methods: We included patients with a laboratory-confirmed SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2) infection admitted in 16 Dutch hospitals participating in the international CAPACITY-COVID registry between March 1 and August 1, 2020. Patients were screened for the occurrence of acute ischemic stroke. We calculated the cumulative incidence of ischemic stroke and compared risk factors, cardiovascular complications, and in-hospital mortality in patients with and without ischemic stroke. Results: We included 2147 patients with COVID-19, of whom 586 (27.3%) needed treatment at an intensive care unit. Thirty-eight patients (1.8%) had an ischemic stroke. Patients with stroke were older but did not differ in sex or cardiovascular risk factors. Median time between the onset of COVID-19 symptoms and diagnosis of stroke was 2 weeks. The incidence of ischemic stroke was higher among patients who were treated at an intensive care unit (16/586; 2.7% versus nonintensive care unit, 22/1561; 1.4%; P=0.039). Pulmonary embolism was more common in patients with (8/38; 21.1%) than in those without stroke (160/2109; 7.6%; adjusted risk ratio, 2.08 [95% CI, 1.52-2.84]). Twenty-seven patients with ischemic stroke (71.1%) died during admission or were functionally dependent at discharge. Patients with ischemic stroke were at a higher risk of in-hospital mortality (adjusted risk ratio, 1.56 [95% CI, 1.13-2.15]) than patients without stroke. Conclusions: In this multicenter cohort study, the cumulative incidence of acute ischemic stroke in hospitalized patients with COVID-19 was approximate to 2%, with a higher risk in patients treated at an intensive care unit. The majority of stroke patients had a poor outcome. The association between ischemic stroke and pulmonary embolism warrants further investigation. Show less
Background In patients with atrial fibrillation who survive an anticoagulation-associated intracerebral haemorrhage, a decision must be made as to whether restarting or permanently avoiding... Show moreBackground In patients with atrial fibrillation who survive an anticoagulation-associated intracerebral haemorrhage, a decision must be made as to whether restarting or permanently avoiding anticoagulation is the best long-term strategy to prevent recurrent stroke and other vascular events. In APACHE-AF, we aimed to estimate the rates of non-fatal stroke or vascular death in such patients when treated with apixaban compared with when anticoagulation was avoided, to inform the design of a larger trial.Methods APACHE-AF was a prospective, randomised, open-label, phase 2 trial with masked endpoint assessment, done at 16 hospitals in the Netherlands. Patients who survived intracerebral haemorrhage while treated with anticoagulation for atrial fibrillation were eligible for inclusion 7-90 days after the haemorrhage. Participants also had a CHA2DS2-VASc score of at least 2 and a score on the modified Rankin scale (mRS) of 4 or less. Participants were randomly assigned (1:1) to receive oral apixaban (5 mg twice daily or a reduced dose of 2.5 mg twice daily) or to avoid anticoagulation (oral antiplatelet agents could be prescribed at the discretion of the treating physician) by a central computerised randomisation system, stratified by the intention to start or withhold antiplatelet therapy in participants randomised to avoiding anticoagulation, and minimised for age and intracerebral haemorrhage location. The primary outcome was a composite of non-fatal stroke or vascular death, whichever came first, during a minimum follow-up of 6 months, analysed using Cox proportional hazards modelling in the intention-to-treat population. APACHE-AF is registered with ClinicalTrials.gov (NCT02565693) and the Netherlands Trial Register (NL4395), and the trial is closed to enrolment at all participating sites.Findings Between Jan 15, 2015, and July 6, 2020, we recruited 101 patients (median age 78 years [IQR 73-83]; 55 [54%] were men and 46 [46%] were women; 100 [99%] were White and one [1%] was Black) a median of 46 days (IQR 21-74) after intracerebral haemorrhage. 50 were assigned to apixaban and 51 to avoid anticoagulation (of whom 26 [51%] started antiplatelet therapy). None were lost to follow-up. Over a median follow-up of 1.9 years (IQR 1.0-3.1; 222 person-years), non-fatal stroke or vascular death occurred in 13 (26%) participants allocated to apixaban (annual event rate 12.6% [95% CI 6.7-21.5]) and in 12 (24%) allocated to avoid anticoagulation (11.9% [95% CI 6.2-20.8]; adjusted hazard ratio 1.05 [95% CI 0.48-2.31]; p=0.90). Serious adverse events that were not outcome events occurred in 29 (58%) of 50 participants assigned to apixaban and 29 (57%) of 51 assigned to avoid anticoagulation.Interpretation Patients with atrial fibrillation who had an intracerebral haemorrhage while taking anticoagulants have a high subsequent annual risk of non-fatal stroke or vascular death, whether allocated to apixaban or to avoid anticoagulation. Our data underline the need for randomised controlled trials large enough to allow identification of subgroups in whom restarting anticoagulation might be either beneficial or hazardous. Copyright (C) 2021 Elsevier Ltd. All rights reserved. Show less
Background In patients with aneurysmal subarachnoid haemorrhage, short-term antifibrinolytic therapy with tranexamic acid has been shown to reduce the risk of rebleeding. However, whether this... Show moreBackground In patients with aneurysmal subarachnoid haemorrhage, short-term antifibrinolytic therapy with tranexamic acid has been shown to reduce the risk of rebleeding. However, whether this treatment improves clinical outcome is unclear. We investigated whether ultra-early, short-term treatment with tranexamic acid improves clinical outcome at 6 months.Methods In this multicentre prospective, randomised, controlled, open-label trial with masked outcome assessment, adult patients with spontaneous CT-proven subarachnoid haemorrhage in eight treatment centres and 16 referring hospitals in the Netherlands were randomly assigned to treatment with tranexamic acid in addition to care as usual (tranexamic acid group) or care as usual only (control group). Tranexamic acid was started immediately after diagnosis in the presenting hospital (1 g bolus, followed by continuous infusion of 1 g every 8 h, terminated immediately before aneurysm treatment, or 24 h after start of the medication, whichever came first). The primary endpoint was clinical outcome at 6 months, assessed by the modified Rankin Scale, dichotomised into a good (0-3) or poor (4-6) clinical outcome. Both primary and safety analyses were according to intention to treat. This trial is registered at ClinicalTrials.gov, NCT02684812.Findings Between July 24, 2013, and July 29, 2019, we enrolled 955 patients; 480 patients were randomly assigned to tranexamic acid and 475 patients to the control group. In the intention-to-treat analysis, good clinical outcome was observed in 287 (60%) of 475 patients in the tranexamic acid group, and 300 (64%) of 470 patients in the control group (treatment centre adjusted odds ratio 0.86, 95% CI 0.66-1.12). Rebleeding after randomisation and before aneurysm treatment occurred in 49 (10%) patients in the tranexamic acid and in 66 (14%) patients in the control group (odds ratio 0.71, 95% CI 0.48-1.04). Other serious adverse events were comparable between groups.Interpretation In patients with CT-proven subarachnoid haemorrhage, presumably caused by a ruptured aneurysm, ultra-early, short-term tranexamic acid treatment did not improve clinical outcome at 6 months, as measured by the modified Rankin Scale. Copyright (C) 2020 Elsevier Ltd. All rights reserved. Show less
