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

Abstract

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.

Global Impact of the COVID-19 Pandemic on Cerebral Venous Thrombosis and Mortality

“…Moreover, the increase in CVT in-hospital mortality during the first 5 months of the COVID-19 pandemic may suggest that patients with milder CVT did not present to stroke centers during the COVID-19 pandemic. Since more than 80% of patients with CVT will have a favorable neurological outcome [ 14 ], patients with milder CVT and particularly those with isolated headache may have been less likely to present in a delayed fashion for persisting deficits and may have been missed altogether.…”

“…Compared to other forms of stroke, the incidence of CVT is more common in younger patients and women. CVT generally has a favorable prognosis with a good 90-day neurological outcome seen in greater than 80% of patients [ 14 - 16 ].…”

Epidemiology and Management of Cerebral Venous Thrombosis during the COVID-19 Pandemic

“…The RESPECT-CVT trial, which compared dabigatran versus warfarin in 120 randomized patients, reported no differences in the safety and efficacy between the groups [ 14 ]. Yaghi and colleagues [ 15 ] performed a retrospective multicentric international observational cohort including over 1000 patients. Real-world cases of CVT that were treated by either warfarin or DOACs were compared.…”

“…Real-world cases of CVT that were treated by either warfarin or DOACs were compared. Patients treated with DOACs presented similar rates of recanalization, death and recurrence, but with lower risk of major hemorrhage, than patients treated with warfarin [ 15 ]. Patients with a clear indication for warfarin (such as presence of anti-phospholipid antibody syndrome) were excluded.…”

ACTION-CVT: Are the Findings ACTIONable?

“…Despite its methodological limitations, ACTION-CVT (Rivaroxaban Compared to Warfarin for Treatment of Cerebral Venous Thrombosis), 6 a pragmatic retrospective study by Yaghi et al, 6 provides added value to the current state of knowledge by virtue of its size and real world setting that is reflective of how DOACs are being used to manage CVT in current clinical practice. The authors provide data from 845 patients across 27 centers in 4 countries from 2015 to 2020.…”