Anticoagulation Timing in Cardioembolic Stroke and Recurrent Event Risk.

OBJECTIVES: Guidelines recommend to initiate anticoagulation within 4-14 days after cardioembolic stroke. Data supporting this did not account for key factors potentially affecting the decision to initiate anticoagulation such as infarct size, hemorrhagic transformation, or high risk features on echocardiography. METHODS: We pooled data from stroke registries of 8 comprehensive stroke centers across the United States. We included consecutive patients admitted with ischemic stroke and atrial fibrillation. The primary predictor was timing of initiating anticoagulation (0-3 days, 4-14 days, or >14 days) and outcomes were recurrent stroke/TIA/systemic embolism, symptomatic intracerebral hemorrhage (sICH), and major extracranial hemorrhage (ECH) within 90 days. RESULTS: Among 2084 patients, 1289 met the inclusion criteria. The combined endpoint occurred in 10.1% (n = 130) subjects (87 ischemic events, 20 sICH, and 29 ECH). Overall, there was no significant difference in the composite endpoint between the three groups: 0-3 days [10.3% (64/617)], 4-14 days [(9.7%) 52/535)], >14 days [10.2% (14/137), p=0.933]. In adjusted models, patients started on anticoagulation between 4-14 days did not have a lower rate of sICH (vs. 0-3 days) (OR 1.49 95% CI 0.50 – 4.43) neither did they have a lower rate of recurrent ischemic events (vs. > 14 days) (OR 0.76 95% CI 0.36 – 1.62, p = 0.482). INTERPRETATION: In this multicenter real world cohort, the recommended (4-14 days) time frame to start oral anticoagulation was not associated with reduced ischemic and hemorrhagic outcomes. Randomized trials are required to determine the optimal timing of anticoagulation initiation

Early ischaemic and haemorrhagic complications after atrial fibrillation-related ischaemic stroke: analysis of the IAC study.

INTRODUCTION: Predictors of long-term ischemic and hemorrhagic complications in atrial fibrillation (AF) have been studied, but there is limited data on predictors of early ischemic and hemorrhagic complications after AF associated ischemic stroke. We sought to determine these predictors. METHODS: The Initiation of Anticoagulation after Cardioembolic stroke (IAC) study is a multicenter retrospective study across that pooled data from consecutive patients with ischemic stroke in the setting of AF from stroke registries across 8 comprehensive stroke centers in the United States. The co-primary outcomes were recurrent ischemic event (stroke/TIA/systemic arterial embolism) and delayed symptomatic intracranial hemorrhage (d-sICH) within 90 days. We performed univariate analyses and cox regression analyses including important predictors on univariate analyses to determine independent predictors of early ischemic events (stroke/TIA/systemic embolism) and d-sICH. RESULTS: Out of 2084 patients, 1520 patients qualified; 104 patients (6.8%) had recurrent ischemic events and 23 patients (1.5%) had d-sICH within 90 days from the index event. In cox-regression models, factors associated with a trend for recurrent ischemic events were prior stroke or TIA (HR 1.42, 0.96 – 2.10) and ipsilateral arterial stenosis with 50–99% narrowing (HR 1.54, 0.98 – 2.43). Those associated with sICH were female sex (HR 2.68, 1.06– 6.83), history of hyperlipidemia (HR 2.91, 1.08 – 7.84), and early hemorrhagic transformation (HR 5.35, 2.22 – 12.92). CONCLUSION: In patients with ischemic stroke and AF, predictors of d-sICH are different than those of recurrent ischemic events therefore recognizing these predictors may help inform early stroke versus d-sICH prevention strategies

Anticoagulation Type and Early Recurrence in Cardioembolic Stroke: The IAC Study.

BACKGROUND AND PURPOSE: In patients with acute ischemic stroke and atrial fibrillation (AF), treatment with low molecular weight heparin (LMWH) increases early hemorrhagic risk without reducing early recurrence and there is limited data comparing warfarin to direct oral anticoagulant (DOAC) therapy. We aim to compare the effects of the treatments above on the risk of 90-day recurrent ischemic events and delayed symptomatic intracranial hemorrhage (d-sICH). METHODS: We included consecutive patients with acute ischemic stroke and AF from the Initiation of Anticoagulation after Cardioembolic stroke (IAC) study pooling data from stroke registries of 8 comprehensive stroke centers across the United States. We compared recurrent ischemic events and d-sICH between each of the following groups in separate cox-regression analyses: 1) DOAC versus warfarin and 2) Bridging with heparin/LMWH versus no bridging, adjusting for pertinent confounders to test these associations. RESULTS: We identified 1,289 patients who met the “bridging versus no bridging” analysis inclusion criteria and 1,251 patients who met the “DOAC versus warfarin” analysis inclusion criteria. In adjusted cox-regression models, bridging (versus no bridging) treatment was associated with a high risk of d-sICH (HR 2.74 95% CI 1.01 – 7.42) but a similar rate of recurrent ischemic events (HR 1.23 95% CI 0.63 – 2.40). Furthermore, DOAC (versus warfarin) treatment was associated with a lower risk of recurrent ischemic events (HR 0.51 95% CI 0.29 – 0.87) but not d-sICH (HR 0.57 95% CI 0.22 – 1.48). CONCLUSION: Our study suggests that patients with ischemic stroke and AF would benefit from the initiation of a DOAC without bridging therapy. Due to our study limitations, these findings should be interpreted with caution pending confirmation from large prospective studies

Factors associated with therapeutic anticoagulation status in patients with ischemic stroke and atrial fibrillation.

BACKGROUND AND PURPOSE: Understanding factors associated with ischemic stroke despite therapeutic anticoagulation is an important goal to improve stroke prevention strategies in patients with atrial fibrillation (AF). We aim to determine factors associated with therapeutic or supratherapeutic anticoagulation status at the time of ischemic stroke in patients with AF. METHODS: The Initiation of Anticoagulation after Cardioembolic stroke (IAC) study is a multicenter study pooling data from stroke registries of eight comprehensive stroke centers across the United States. Consecutive patients hospitalized with acute ischemic stroke in the setting of AF were included in the IAC cohort. For this study, we only included patients who reported taking warfarin at the time of the ischemic stroke. Patients not on anticoagulation and patients who reported use of a direct oral anticoagulant were excluded. Analyses were stratified based on therapeutic (INR ≥2) versus subtherapeutic (INR <2) anticoagulation status. We used binary logistic regression models to determine factors independently associated with anticoagulation status after adjustment for pertinent confounders. In particular, we sought to determine whether atherosclerosis with 50% or more luminal narrowing in an artery supplying the infarct (a marker for a competing atherosclerotic mechanism) and small stroke size (≤ 10 mL; implying a competing small vessel disease mechanism) related to anticoagulant status. RESULTS: Of the 2084 patients enrolled in the IAC study, 382 patients met the inclusion criteria. The mean age was 77.4 ± 10.9 years and 52.4% (200/382) were men. A total of 222 (58.1%) subjects presented with subtherapeutic INR. In adjusted models, small stroke size (OR 1.74 95% CI 1.10 – 2.76, p = 0.019) and atherosclerosis with 50% or more narrowing in an artery supplying the infarct (OR 1.96 95% CI 1.06 – 3.63, p = 0.031) were independently associated with INR ≥2 at the time of their index stroke. CONCLUSION: Small stroke size (≤ 10 ml) and ipsilateral atherosclerosis with 50% or more narrowing may indicate a competing stroke mechanism. There may be important opportunities to improve stroke prevention strategies for patients with AF by targeting additional ischemic stroke mechanisms to improve patient outcomes

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 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 \u3c 0.001) and the presence of one or more positive antiphospholipid antibodies (aHR 3.85, 95% CI 1.97-7.50, p \u3c 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]; =0.84), death (aHR, 0.78 [95% CI, 0.22-2.76]; =0.70), and rate of partial/complete recanalization (aOR, 0.92 [95% CI, 0.48-1.73]; =0.79), but a lower risk of major hemorrhage (aHR, 0.35 [95% CI, 0.15-0.82]; =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

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