Background and Purpose: With the spread of coronavirus disease 2019 (COVID-19) during the current worldwide pandemic, there is mounting evidence that patients affected by the illness may develop clinically significant coagulopathy with thromboembolic complications including ischemic stroke. However, there is limited data on the clinical characteristics, stroke mechanism, and outcomes of patients who have a stroke and COVID-19. Methods: We conducted a retrospective cohort study of consecutive patients with ischemic stroke who were hospitalized between March 15, 2020, and April 19, 2020, within a major health system in New York, the current global epicenter of the pandemic. We compared the clinical characteristics of stroke patients with a concurrent diagnosis of COVID-19 to stroke patients without COVID-19 (contemporary controls). In addition, we compared patients to a historical cohort of patients with ischemic stroke discharged from our hospital system between March 15, 2019, and April 15, 2019 (historical controls). Results: During the study period in 2020, out of 3556 hospitalized patients with diagnosis of COVID-19 infection, 32 patients (0.9%) had imaging proven ischemic stroke. Cryptogenic stroke was more common in patients with COVID-19 (65.6%) as compared to contemporary controls (30.4%, P =0.003) and historical controls (25.0%, P <0.001). When compared with contemporary controls, COVID-19 positive patients had higher admission National Institutes of Health Stroke Scale score and higher peak D-dimer levels. When compared with historical controls, COVID-19 positive patients were more likely to be younger men with elevated troponin, higher admission National Institutes of Health Stroke Scale score, and higher erythrocyte sedimentation rate. Patients with COVID-19 and stroke had significantly higher mortality than historical and contemporary controls. Conclusions: We observed a low rate of imaging-confirmed ischemic stroke in hospitalized patients with COVID-19. Most strokes were cryptogenic, possibly related to an acquired hypercoagulability, and mortality was increased. Studies are needed to determine the utility of therapeutic anticoagulation for stroke and other thrombotic event prevention in patients with COVID-19.
Purpose: Central retinal artery occlusion (CRAO) is a form of acute ischemic stroke that causes severe visual loss and is a harbinger of further cerebrovascular and cardiovascular events. There is a paucity of scientific information on the appropriate management of CRAO, with most strategies based on observational literature and expert opinion. In this scientific statement, we critically appraise the literature on CRAO and provide a framework within which to consider acute treatment and secondary prevention. Methods: We performed a literature review of randomized controlled clinical trials, prospective and retrospective cohort studies, case-control studies, case reports, clinical guidelines, review articles, basic science articles, and editorials concerning the management of CRAO. We assembled a panel comprising experts in the fields of vascular neurology, neuro-ophthalmology, vitreo-retinal surgery, immunology, endovascular neurosurgery, and cardiology, and document sections were divided among the writing group members. Each member received an assignment to perform a literature review, synthesize the data, and offer considerations for practice. Multiple drafts were circulated among the group until consensus was achieved. Results: Acute CRAO is a medical emergency. Systems of care should evolve to prioritize early recognition and triage of CRAO to emergency medical attention. There is considerable variability in management patterns among practitioners, institutions, and subspecialty groups. The current literature suggests that treatment with intravenous tissue plasminogen activator may be effective. Patients should undergo urgent screening and treatment of vascular risk factors. There is a need for high-quality, randomized clinical trials in this field.
Background and Purpose: While the thrombotic complications of COVID-19 have been well described, there are limited data on clinically significant bleeding complications including hemorrhagic stroke. The clinical characteristics, underlying stroke mechanism, and outcomes in this particular subset of patients are especially salient as therapeutic anticoagulation becomes increasingly common in the treatment and prevention of thrombotic complications of COVID-19. Methods: We conducted a retrospective cohort study of patients with hemorrhagic stroke (both non-traumatic intracerebral hemorrhage and spontaneous non-aneurysmal subarachnoid hemorrhage) who were hospitalized between March 1, 2020, and May 15, 2020, within a major healthcare system in New York, during the coronavirus pandemic. Patients with hemorrhagic stroke on admission and who developed hemorrhage during hospitalization were both included. We compared the clinical characteristics of patients with hemorrhagic stroke and COVID-19 to those without COVID-19 admitted to our hospital system between March 1, 2020, and May 15, 2020 (contemporary controls), and March 1, 2019, and May 15, 2019 (historical controls). Demographic variables and clinical characteristics between the individual groups were compared using Fischer's exact test for categorical variables and nonparametric test for continuous variables. We adjusted for multiple comparisons using the Bonferroni method. Results: During the study period in 2020, out of 4071 patients who were hospitalized with COVID-19, we identified 19 (0.5%) with hemorrhagic stroke. Of all COVID-19 with hemorrhagic stroke, only three had isolated non-aneurysmal SAH with no associated intraparenchymal hemorrhage. Among hemorrhagic stroke in patients with COVID-19, coagulopathy was the most common etiology (73.7%); empiric anticoagulation was started in 89.5% of these patients versus 4.2% in contemporary controls (p ≤ .001) and 10.0% in historical controls (p ≤ .001). Compared to contemporary and historical controls, patients with COVID-19 had higher initial NIHSS scores, INR, PTT, and fibrinogen levels. Patients with COVID-19 also had higher rates of in-hospital mortality (84.6% vs. 4.6%, p ≤ 0.001). Sensitivity analyses excluding patients with strictly subarachnoid hemorrhage yielded similar results.
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.
Background and Purpose— Left atrial enlargement has been shown to be associated with ischemic stroke, but the association with embolic stroke mechanisms remains unknown. We aim to study the associations between left atrial volume index (LAVI) and embolic stroke subtypes and atrial fibrillation (AF) detection on cardiac event monitoring in patients with embolic stroke of unknown source. Methods— Data were collected from a prospective cohort of consecutive patients with ischemic stroke admitted to a comprehensive stroke center over 18 months. Stroke subtype was classified into cardioembolic stroke, noncardioembolic stroke of determined mechanism (NCE), or embolic stroke of undetermined source (ESUS). Univariate and prespecified multivariable analyses were performed to assess associations between LAVI and stroke subtype and AF detection in patients with ESUS. Results— Of 1224 consecutive patients identified during the study period, 1020 (82.6%) underwent transthoracic echocardiography and had LAVI measurements. LAVI was greater in patients with cardioembolic stroke than NCE (41.4 mL/m 2 ±18.0 versus 28.6 mL/m 2 ±12.2; P <0.001) but not in ESUS versus NCE (28.9 mL/m 2 ±12.6 versus 28.6 mL/m 2 ±12.2; P =0.61). In multivariable logistic regression models, LAVI was greater in cardioembolic stroke versus NCE (adjusted odds ratio per mL/m 2 , 1.07; 95% CI, 1.05–1.09; P <0.001) but not in ESUS versus NCE (adjusted odds ratio per mL/m 2 , 1.00; 95% CI, 0.99–1.02; P =0.720). Among 99 patients with ESUS who underwent cardiac monitoring, 18.2% had AF detected; LAVI was independently associated with AF detection in ESUS (adjusted odds ratio per mL/m 2 , 1.09; 95% CI, 1.02–1.15; P =0.007). Conclusions— LAVI is associated with cardioembolic stroke as well as AF detection in patients with ESUS, 2 subsets of ischemic stroke that benefit from anticoagulation therapy. Patients with increased LAVI may be a subgroup where anticoagulation may be tested for stroke prevention.
Background and purposeA subset of ischaemic stroke patients with atrial fibrillation (AF) have ischaemic stroke despite anticoagulation. We sought to determine the association between prestroke anticoagulant therapy and recurrent ischaemic events and symptomatic intracranial haemorrhage (sICH).MethodsWe included consecutive patients with acute ischaemic stroke and AF from the Initiation of Anticoagulation after Cardioembolic stroke (IAC) study from eight comprehensive stroke centres in the USA. We compared recurrent ischaemic events and delayed sICH risk using adjusted Cox regression analyses between patients who were prescribed anticoagulation (ACp) versus patients who were naïve to anticoagulation therapy prior to the ischaemic stroke (anticoagulation naïve).ResultsAmong 2084 patients in IAC, 1518 had prior anticoagulation status recorded and were followed for 90 days. In adjusted Cox hazard models, ACp was associated with some evidence of a higher risk higher risk of 90-day recurrent ischaemic events only in the fully adjusted model (adjusted HR 1.50, 95% CI 0.99 to 2.28, p=0.058) but not increased risk of 90-day sICH (adjusted HR 1.08, 95% CI 0.46 to 2.51, p=0.862). In addition, switching anticoagulation class was not associated with reduced risk of recurrent ischaemic events (adjusted HR 0.41, 95% CI 0.12 to 1.33, p=0.136) nor sICH (adjusted HR 1.47, 95% CI 0.29 to 7.50, p=0.641).ConclusionAF patients with ischaemic stroke despite anticoagulation may have higher recurrent ischaemic event risk compared with anticoagulation-naïve patients. This suggests differing underlying pathomechanisms requiring different stroke prevention measures and identifying these mechanisms may improve secondary prevention strategies.
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