Predictors of Recurrent Venous Thrombosis After Cerebral Venous Thrombosis: Analysis of the ACTION-CVT Study.

BACKGROUND and Purpose: Cerebral venous thrombosis (CVT) is a rare cause of stroke carrying a nearly 4% risk of recurrence after 1 year. There is limited data on predictors of recurrent venous thrombosis in patients with CVT. In this study, we aim to identify those predictors. METHODS This is a secondary analysis of the ACTION-CVT study which is a multi-center international study of consecutive patients hospitalized with a diagnosis of CVT over a 6-year period. Patients with cancer associated CVT, CVT during pregnancy, or CVT in the setting of known antiphospholipid antibody syndrome were excluded per the ACTION-CVT protocol. The study outcome was recurrent venous thrombosis defined as recurrent venous thromboembolism (VTE) or de-novo CVT. We compared characteristics between patients with vs. without recurrent venous thrombosis during follow-up and performed adjusted Cox regression analyses to determine important predictors of recurrent venous thrombosis. RESULTS 947 patients were included with a mean age was 45.2 years, 63.9% were women, and 83.6% had at least 3-months of follow-up. During a median follow-up of 308 (IQR 120-700) days, there were 5.05 recurrent venous thromboses (37 VTE and 24 de-novo CVT) per 100 patient-years. Predictors of recurrent venous thrombosis were Black race (adjusted HR 2.13, 95% CI 1.14-3.98, p = 0.018), prior history of VTE (aHR 3.40, 95% CI 1.80-6.42, p < 0.001) and the presence of one or more positive antiphospholipid antibodies (aHR 3.85, 95% CI 1.97-7.50, p < 0.001). Sensitivity analyses including events only occurring on oral anticoagulation yielded similar findings. CONCLUSION Black race, history of VTE, and the presence of one or more antiphospholipid antibodies are associated with recurrent venous thrombosis among patients with CVT. Future studies are needed to validate our findings to better understand mechanisms and treatment strategies in patients with CVT

Direct Oral Anticoagulants Versus Warfarin in the Treatment of Cerebral Venous Thrombosis (ACTION-CVT): A Multicenter International Study.

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

Antithrombotic Treatment for Stroke Prevention in Cervical Artery Dissection: The STOP-CAD Study.

Background: Small, randomized trials of cervical artery dissection (CAD) patients showed conflicting results regarding optimal stroke prevention strategies. We aimed to compare outcomes in patients with CAD treated with antiplatelets versus anticoagulation. Methods: This is a multi-center observational retrospective international study (16 countries, 63 sites) that included CAD patients without major trauma. The exposure was antithrombotic treatment type (anticoagulation vs. antiplatelets) and outcomes were subsequent ischemic stroke and major hemorrhage (intracranial or extracranial hemorrhage). We used adjusted Cox regression with Inverse Probability of Treatment Weighting (IPTW) to determine associations between anticoagulation and study outcomes within 30 and 180 days. The main analysis used an "as treated" cross-over approach and only included outcomes occurring on the above treatments. Results: The study included 3,636 patients [402 (11.1%) received exclusively anticoagulation and 2,453 (67.5%) received exclusively antiplatelets]. By day 180, there were 162 new ischemic strokes (4.4%) and 28 major hemorrhages (0.8%); 87.0% of ischemic strokes occurred by day 30. In adjusted Cox regression with IPTW, compared to antiplatelet therapy, anticoagulation was associated with a non-significantly lower risk of subsequent ischemic stroke by day 30 (adjusted HR 0.71 95% CI 0.45-1.12, p=0.145) and by day 180 (adjusted HR 0.80 95% CI 0.28-2.24, p=0.670). Anticoagulation therapy was not associated with a higher risk of major hemorrhage by day 30 (adjusted HR 1.39 95% CI 0.35-5.45, p=0.637) but was by day 180 (adjusted HR 5.56 95% CI 1.53-20.13, p=0.009). In interaction analyses, patients with occlusive dissection had significantly lower ischemic stroke risk with anticoagulation (adjusted HR 0.40 95% CI 0.18-0.88) (Pinteraction=0.009). Conclusions: Our study does not rule out a benefit of anticoagulation in reducing ischemic stroke risk, particularly in patients with occlusive dissection. If anticoagulation is chosen, it seems reasonable to switch to antiplatelet therapy before 180 days to lower the risk of major bleeding. Large prospective studies are needed to validate our findings