Babak Benjamin Navi

Background: Patients with acute ischemic stroke and active cancer face high risks of recurrent stroke and death. Evidence guiding antithrombotic selection remains limited. Aims: To investigate post–acute ischemic stroke prescribing patterns of antiplatelet versus anticoagulant therapy in acute ischemic stroke patients with active cancer and their associated clinical characteristics and outcomes. Methods: We retrospectively analyzed 2003–2024 data from the Acute Stroke Registry and Analysis of Lausanne. We included patients with active cancer discharged after index acute ischemic stroke on antiplatelet therapy (single or dual) or anticoagulation (±antiplatelet therapy). We excluded patients with no or inactive cancer, missing data on discharge antithrombotics, cancer diagnosed after hospitalization, and those who died or entered palliative care before treatment decisions. The primary outcome was a recurrent ischemic cerebrovascular event within 12 months. Secondary outcomes included 3-month ischemic cerebrovascular recurrence, modified Rankin Scale shift, and all-cause mortality. The safety outcome was symptomatic intracranial hemorrhage at 3 and 12 months. We used multivariable regression models adjusted for prognostic variables. Results: Among 8035 patients with acute ischemic stroke, 313 had active cancer and met eligibility criteria. Median age was 73 years (interquartile range = 63–79), and 111 (35%) were women. At discharge, 178 (57%) received antiplatelet therapy and 135 (43%) anticoagulation. Patients previously naïve to antithrombotic therapy ( n = 150) more often received antiplatelet therapy (68% vs 32%, p < 0.001). At 12 months, ischemic cerebrovascular recurrence occurred in 28/160 (18%) patients in the antiplatelet group and 33/118 (28%) in the anticoagulation group (subdistribution hazard ratio = 0.59, 95% confidence interval = 0.33–1.04). At 3 months, the antiplatelet group had lower risks of ischemic cerebrovascular recurrence (subdistribution hazard ratio = 0.45, 95% confidence interval = 0.25–0.82) and all-cause mortality (adjusted hazard ratio = 0.61, 95% confidence interval = 0.41–0.90). Mortality at 12 months (adjusted hazard ratio = 1.16, 95% confidence interval = 0.62–2.16) and modified Rankin Scale shift at 3 months (adjusted odds ratio = 0.79, 95% confidence interval = 0.49–1.26) and 12 months (adjusted odds ratio = 0.81, 95% confidence interval = 0.48–1.37) were similar between groups. No intracranial hemorrhages were recorded. Conclusion: In a registry spanning two decades, most patients with active cancer were discharged on antiplatelet therapy after acute ischemic stroke. Antiplatelet and anticoagulant groups showed similar long-term risks of ischemic cerebrovascular recurrence. Antiplatelet therapy was associated with reduced medium-term ischemic cerebrovascular recurrences and mortality, although between-group clinical differences may have contributed to these findings. Data access statement: Anonymized data are available from the corresponding author upon reasonable request and subject to a signed data transfer and use agreement.

Background and ObjectivesCancer is associated with vascular disease. Modern cancer treatments, particularly targeted agents and immunotherapy, have extended survival from cancer. We aimed to determ...

BACKGROUND: Recent years have seen improvements in stroke-care pathways, including mobile stroke units (MSUs), and this may have affected the rate, predictors, and outcomes of patients with acute ischemic stroke who qualify for but do not receive treatment with intravenous thrombolysis (IVT). METHODS: This was a secondary observational cohort analysis of the prospective, multicenter BEST-MSU trial (Benefits of Stroke Treatment Delivered by a Mobile Stroke Unit Compared With Standard Management by Emergency Medical Services), conducted in 7 US cities from 2014 to 2020, comparing MSU management versus standard emergency department management for patients with suspected acute ischemic stroke. The analytical cohort comprised enrolled patients with confirmed acute ischemic stroke and no guideline contraindications to IVT. The outcome was a potential missed IVT opportunity, defined as patients not treated with IVT despite lacking contraindications. We used multivariable logistic regression to evaluate whether demographics, prestroke modified Rankin Scale, study site, comorbidities, National Institutes of Health Stroke Scale, blood pressure, international normalized ratio, glucose, antithrombotic use, and thrombectomy were associated with this outcome. RESULTS: Of 1515 enrolled patients, 927 met criteria for this analysis. Fifty-one participants (5.5%) had a potential missed IVT opportunity, including 4 of 555 (0.7%) in the MSU group versus 47 of 372 (12.6%) in the emergency department group (odds ratio, 0.05 [95% CI, 0.02–0.12]). In multivariable analysis, omitting study group, lower National Institutes of Health Stroke Scale (odds ratio, 0.95 [95% CI, 0.90–0.99]) and longer last known well-to-door time (odds ratio per 10 minutes, 1.08 [95% CI, 1.03–1.13]) were independently associated with a potential missed IVT opportunity. The leading reasons documented for withholding IVT were resolving symptoms (43%), time window concerns (18%), and minor deficits (10%). Among participants with a potential missed IVT opportunity and a recorded 3-month modified Rankin Scale (n=49), 19 (39%) had a score of 3 to 6. CONCLUSIONS: In the BEST-MSU trial, potential missed IVT opportunities occurred in 1-in-8 patients in the emergency department, and rarely on the MSU. Although often due to early improvement or minor deficits, more than one-third of these patients had poor functional status at 3 months. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02190500.

BACKGROUND: In patients with cryptogenic stroke, the characteristics of multiterritory brain infarcts, the recurrent stroke risk, and the response to anticoagulation remain unclear. METHODS: The ARCADIA trial (Atrial Cardiopathy and Antithrombotic Drugs in Prevention After Cryptogenic Stroke) screened patients with cryptogenic stroke for atrial cardiopathy at 185 centers in the United States and Canada from 2018 to 2022. Investigators reported baseline acute brain infarction in the left anterior, right anterior, and posterior circulation. Atrial cardiopathy was defined as P-wave terminal force in ECG lead V1s >5000 μV·ms, NT-proBNP (N-terminal pro-B-type natriuretic peptide) >250 pg/mL, or left atrial diameter index ≥3 cm/m ² . Site echocardiography laboratories determined left atrial diameter index and a central echocardiography laboratory determined LVEF. We used ANCOVA to examine whether atrial cardiopathy biomarkers or LVEF were associated with the number of territories with infarction. Cox regression was used to examine whether the number of infarct territories was associated with recurrent stroke or modified the effect of apixaban compared with aspirin. RESULTS: Among 3464 patients with reported baseline magnetic resonance imaging data, 220 (6.4%) had no visible acute infarct and 2794 (80.7%) had acute infarction in 1, 374 (10.8%) in 2, and 76 (2.2%) in 3 territories. Atrial cardiopathy biomarkers and LVEF were not associated with the number of infarct territories. Among 937 of these 3464 patients who were randomized, we found higher risks of recurrent stroke associated with infarcts in 2 territories (hazard ratio, 2.4 [95% CI, 1.3–4.2]) or 3 territories (hazard ratio, 3.7 [95% CI, 1.5–9.3]) relative to single-territory infarction, whereas the absence of visible infarction was not associated with recurrence (hazard ratio, 1.8 [95% CI, 0.6–4.9]). The number of infarct territories did not modify the effect of apixaban versus aspirin in relation to recurrent stroke ( P for interaction, 0.71). CONCLUSIONS: Multiterritory brain infarction was not associated with atrial cardiopathy biomarkers or LVEF in the ARCADIA trial. Multiterritory infarction was associated with a significantly higher risk of recurrent stroke, but this heightened risk was not reduced by apixaban relative to aspirin.

Objective: The relative risks of bleeding with apixaban and aspirin remain unclear. We compared bleeding end points on apixaban versus aspirin in the ARCADIA trial. Methods: ARCADIA was a multicenter, double‐blind, randomized trial of apixaban versus aspirin in patients with cryptogenic stroke and evidence of atrial cardiopathy. International Society on Thrombosis and Hemostasis (ISTH) criteria were used to classify bleeding as intracranial, symptomatic intracranial, major non‐intracranial hemorrhages, and any major and minor hemorrhages. We calculated annualized incidence rate differences (IRDs) between apixaban and aspirin. Our primary analysis included the safety sample which censored patients who permanently stopped taking the study drug. Sensitivity analyses included the intention‐to‐treat sample. Results: Among 1,015 patients assigned to apixaban or aspirin and followed for a mean 1.8 (±1.2) years, 115 (11.3%) patients experienced 146 hemorrhages: 27 (18.5%) major and 119 (81.5%) minor hemorrhages. Apixaban resulted in significantly fewer intracranial hemorrhages than aspirin in both the safety sample (IRD = −1.4%, 95% confidence interval [CI] = −2.3% to −0.5%) and intention‐to‐treat sample (IRD = −1.0%, 95% CI = −1.8% to −0.2%). Findings were similar for the risk of symptomatic intracranial hemorrhage in the safety sample (IRD = −1.1%, 95% CI = −1.8% to −0.3%), although this was not statistically significant in the sensitivity analysis of the intention‐to‐treat sample (IRD = −0.7%, 95% CI = −1.4% to 0.0%, p = 0.11). Risks of major non‐intracranial hemorrhage, any major hemorrhage, and minor hemorrhage did not differ significantly between apixaban and aspirin. Interpretation: We found no increase in any hemorrhage type and a decrease in intracranial hemorrhage with apixaban relative to aspirin in patients with cryptogenic stroke and evidence of atrial cardiopathy. ANN NEUROL 2026;99:1589–1597

Ischemic stroke and cancer often coexist. The aim of this study was to determine the prevalence of cancer among patients with stroke, their antithrombotic treatment patterns, and the risk of subsequent thromboembolic events in a large population-based cohort. This retrospective cohort study used data from Optum's deidentified Clinformatics Data Mart Database to assess the 6-month risk of recurrent thromboembolic and major bleeding events identified using validated International Classification of Diseases code algorithms, among adults with active cancer hospitalized with ischemic stroke between October 2020 and September 2021. In addition, we explored the risk of recurrent thromboembolic events stratified by anticoagulant exposure. Landmark analyses were undertaken with anticoagulant exposure status based on dispensations in the week after hospital discharge. Propensity score matching aimed to minimize selection bias between the groups. Hazard ratios (HRs) were estimated using Cox proportional hazard models with robust variance estimators to account for clustering within propensity score-matched pairs. Among 86,365 patients identified with ischemic stroke, 10.2% had active cancer (most common types: 34% genitourinary, 25% gastrointestinal, 23% hematologic). After applying eligibility criteria, 4,781 patients were included in the main analysis (median age 74 [interquartile range 68-81] years; 48% female). Anticoagulants were dispensed to 14.7% of patients. The incidence of thromboembolic event recurrence and major bleeding events was 38.4 (95% CI 35.4-41.6) and 20.9 (95% CI 18.8-23.4) per 100 person-years, respectively. After propensity score matching, the risk of thromboembolism recurrence was not statistically different between those with and without anticoagulant prescription (HR 1.21; 95% CI 0.91-1.61). Anticoagulant prescription was also not associated with a higher risk of major bleeding events (HR 1.13; 95% CI 0.78-1.63). In this large-scale study, approximately 10% of patients with ischemic stroke had active cancer and they faced a markedly elevated short-term risk of recurrent thromboembolism and major bleeding events. Anticoagulants were infrequently prescribed after discharge and did not differentially affect the rate of ischemic or bleeding outcomes compared with alternative treatment strategies, although confounding by indication is likely. Clinical trials are required to further assess optimal antithrombotic strategies in this high-risk population.

Objective: There are limited population‐based data regarding the prevalence of cerebral amyloid angiopathy (CAA) and associated risks of mortality and incident cerebrovascular events.Methods: We performed a retrospective cohort study using inpatient and outpatient claims from 2008 to 2022 from a 5% national sample of Medicare beneficiaries. CAA and ischemic and hemorrhagic stroke were identified using validated International Classification of Diseases 10th Revision (ICD‐10) codes. We ascertained CAA from October 1, 2015 through 2022, and used data from 2008 through September 30, 2015 to ascertain comorbidities including prevalent stroke. We used Cox regression to examine the association of CAA with subsequent death and incident stroke subtypes after adjustment for demographics, vascular risk factors, and Charlson comorbidities.Results: Among 1,920,312 Medicare beneficiaries in our sample, 2,161 (11.3 per 10,000) had a diagnosis of CAA. In adjusted Cox regression analysis, there was an association between CAA and subsequent mortality (HR 4.9; 95% CI 4.6–5.2). Among 1,872,474 patients without prevalent stroke, including 900 of the CAA patients, there was a significant association between CAA and an increased risk of any stroke (HR 8.0; 95% CI 6.7–9.6), ischemic stroke (HR 4.6; 95% CI 3.6–6.0), intracerebral hemorrhage (HR 26.9; 95% CI 20.3–35.6), and subarachnoid hemorrhage (HR 21.6; 95% CI 12.2–38.1). After a diagnosis of CAA, absolute risks of ischemic stroke and intracerebral hemorrhage were broadly similar.Interpretation: In a large, nationwide cohort of Medicare beneficiaries, the prevalence of clinically diagnosed CAA was approximately 11 per 10,000. CAA was associated with an increased risk of mortality and incident stroke, both hemorrhagic and ischemic. ANN NEUROL 2025;98:249–257

Aims: Endometriosis frequently affects reproductive aged females and is associated with increased cardiovascular disease risk. The aims of this study were (i) to confirm the relationship between cardiovascular disease and endometriosis and (ii) to test whether aspirin modified the effect of endometriosis on cardiovascular disease risk. Methods and results: A longitudinal cohort study was conducted using data from the California Teachers Study from enrolment (1995–1996) through the current administrative end follow-up (31 December 2020). Primary outcome was any incident major adverse cardiovascular event (MACE) defined using validated ICD-9/ICD-10 codes for stroke, myocardial infarction, and coronary heart disease. Inverse probability (IP) weights were used to estimate the causal effect of self-reported endometriosis on cardiovascular events. Of the included 120 435 participants, 13 754 (11.4%) reported history of endometriosis. There were 2159 admissions for MACE in the endometriosis group vs. 16 632 in the non-endometriosis group. After controlling for demographics and vascular comorbidities, risk of MACE was higher in the endometriosis group than in the non-endometriosis group [IP-weighted hazard ratio (HR) 1.10, confidence interval (CI) 1.04–1.15], particularly in participants < 40 years of age (IP-weighted HR 1.48, CI 1.08–2.02). Aspirin use did not modify the effect of endometriosis on MACE (P interaction = 0.467). Among participants taking aspirin, the adjusted HR for endometriosis was 1.07 (95% CI, 0.96–1.19) whereas among participants not taking aspirin, adjusted HR was 1.10 (95% CI, 1.04–1.17). Conclusion: In a large American cohort, endometriosis was associated with increased risk of adverse cardiovascular events, especially in younger participants. Aspirin did not modify this risk. Research to determine how to best reduce cardiovascular risk in endometriosis is warranted.