Skylar Lewis

BACKGROUND: Cerebral venous thrombosis is an uncommon cause of stroke that primarily affects young adults. Several clinical trials and observational studies have compared vitamin K antagonists (VKAs) with direct oral anticoagulants (DOACs) for treating cerebral venous thrombosis, but the small sample sizes limit the ability to draw firm conclusions. METHODS: We performed a systematic review and meta-analysis of randomized controlled trials and observational studies comparing DOACs with VKAs for the treatment of cerebral venous thrombosis. Studies published between January 2007 and July 2025 were included. Prespecified subgroup analyses were conducted by study design, DOAC class (anti–factor Xa inhibitors versus direct thrombin inhibitors), and VKA. Risk of bias was assessed using the Cochrane Risk-of-Bias Tool 2 for randomized trials and the Risk of Bias in Nonrandomized Studies of Interventions for observational studies. Pooled risk ratios (RRs) with 95% CIs were calculated using random-effects models. RESULTS: Fourteen studies (8 randomized clinical trials [RCTs] and 6 observational studies) were included. Among 3698 patients, 1669 (45.1%) received DOACs and 2029 (54.9%) received VKAs. Rates of recurrent venous thromboembolism (10.24% versus 10.99%), major bleeding (4.26% versus 6.18%), clinically relevant nonmajor bleeding (2.63% versus 1.66%), good functional outcomes (95.09% versus 89.25%), and mortality (3.37% versus 3.30%) were similar in DOACs and VKAs. Recurrent venous thromboembolism was similar between DOACs and VKAs in RCTs (RR, 1.06 [95% CI, 0.35–3.24]) and in the overall pooled analysis of all studies (RR, 0.92 [95% CI, 0.55–1.53]). Major bleeding did not differ between DOACs and VKAs in RCTs (RR, 0.73 [95% CI, 0.24–2.22]) or in the overall analysis (RR, 0.74 [95% CI, 0.44–1.25]; P =0.26). Clinically relevant nonmajor bleeding was also comparable in RCTs (RR, 1.06 [95% CI, 0.25–4.48]) and overall (RR, 1.22 [95% CI, 0.38–3.86]). Good functional outcomes (modified Rankin Scale score of 0–2) were similar between DOACs and VKAs in RCTs (RR, 1.00 [95% CI, 0.84–1.19]) and in the combined analysis of all studies (RR, 1.02 [95% CI, 0.93–1.11]). Mortality was similar between DOACs and VKAs in RCTs (RR, 1.15 [95% CI, 0.28–4.68]) and in the pooled analysis. When direct thrombin inhibitors were compared with factor Xa inhibitors, there were no significant differences in outcomes. CONCLUSIONS: DOACs demonstrated comparable efficacy and safety to VKAs in the treatment of cerebral venous thrombosis. These findings support the use of DOACs as a reasonable alternative.

Background: Although the embolic stroke of undetermined source (ESUS) construct was proposed as a unifying concept for embolic‐appearing strokes without an identified cause, it includes patients with diverse and often unrecognized underlying mechanisms. This study investigates the differential rate of recurrent stroke according to the completeness of neurodiagnostic testing in a diverse multicenter cohort. Methods: This was a retrospective analysis of a multicenter observational cohort study (n=27 sites). ESUS was categorized into 3 groups: (1) established mechanism after further workup (ESUS‐E), (2) comprehensive diagnostic workup without an identified cause (ESUS 2.0), and (3) no advanced workup. The primary outcome of recurrent ischemic stroke was compared between ESUS with established mechanism and ESUS 2.0 versus ESUS with no advanced workup and was assessed using adjusted Cox proportional hazards models. Results: Among 2281 patients, the mean age was 65 years, and 50.1% were men. 694 (30.4%) classified as ESUS‐E, 1,243 (54.5%) classified as ESUS‐NAW, and 344 (15.1%) as ESUS 2.0. The ESUS 2.0 group had a significantly lower risk of recurrent stroke than both the group with ESUS with no advanced workup (adjusted hazard ratio [aHR], 0.31 [95% CI, 0.13–0.76]) and the group with ESUS with established mechanism (aHR, 0.35 [95% CI, 0.15–0.85]). Within the group with ESUS with established mechanism, cancer (aHR, 5.33 [95% CI, 2.09–13.63]) and nonstenosing atherosclerotic disease or arch atheroma (aHR, 3.40 [95% CI, 1.18–9.83]) were associated with significantly increased risk of recurrence when compared with the group with ESUS 2.0. Conclusions: These findings demonstrate a lower risk of recurrent stroke in patients classified as ESUS 2.0 than reported in prior ESUS trials and highlight the importance of age‐appropriate advanced diagnostic evaluation. Registration: URL: https://www.clinicaltrials.gov . Identifier: NCT06398366.

Background and ObjectivesMultiple clinical trials have failed to show benefit of anticoagulation over antiplatelets in preventing recurrent stroke among patients with embolic stroke of undetermined...

Background and ObjectivesCarotid artery web (CW) is an underrecognized cause of ischemic stroke that promotes blood stasis and embolization despite non–flow-limiting stenosis. The clot phenotype of...