Novel factor xa inhibitor for the treatment of cerebral venous and sinus thrombosis: first experience in 7 patients.

Thrombosis of cerebral veins and sinus (cerebral venous thrombosis) is a rare stroke pathogenesis. Pharmaceutical treatment is restricted to heparin and oral anticoagulation with vitamin K antagonists (VKAs). Between January 2012 and December 2013, we recorded data from our patients with cerebral venous thrombosis. The modified Rankin scale was used to assess clinical severity; excellent outcome was defined as modified Rankin scale 0 to 1. Recanalization was assessed on follow-up MR angiography. Patients were then divided into 2 treatment groups: phenprocoumon (VKA) and a novel factor Xa inhibitor. Clinical and radiological baseline data, outcome, recanalization status, and complications were retrospectively compared. Sixteen patients were included, and 7 were treated with rivaroxaban. Overall outcome was excellent in 93.8%, and all patients showed at least partial recanalization. No statistical significant differences were found between the groups, except the use of heparin before start of oral anticoagulation (P=0.03). One patient in the VKA and 2 patients in the factor Xa inhibitor group had minor bleeding (P=0.55) within the median (range) follow-up of 8 months (5-26). Factor Xa inhibitor showed a similar clinical benefit as VKA in the treatment of cerebral venous thrombosis. Further systematic prospective evaluation is warranted.

Geisbüsch C ，Richter D ，Herweh C ，Ringleb PA ，Nagel S ... -  《-》

Is it safe to treat cerebral venous thrombosis with oral rivaroxaban without heparin? A preliminary study from 20 patients.

Newer oral anticoagulants like rivaroxaban are increasingly becoming the mainstay of treatment in systemic thrombosis. However cerebral venous thrombosis (CVT) is conventionally treated with heparin followed by oral vitamin K antagonists. Currently very little information is available about the use of rivaroxaban in CVT. Rivaroxaban has been used only after the initial treatment with heparin in the available studies. All patients with CVT between January 2017 and June 2017 were initiated directly on oral rivaroxaban. Critically ill patients including those requiring surgical intervention were excluded. The modified Rankin scale was used to assess clinical severity and a scale of 0-1 was defined as excellent outcome. Recanalization was assessed at 3 months follow-up with MR angiography. Complications of the drug including bleeding episodes during treatment and at follow-up were noted. Twenty patients were initiated on rivaroxaban and followed up for a mean duration of 6 months. Eighty percent (16/20) were males and the mean age was 34.1 years. Associated cerebral hemorrhagic infarcts were seen in 11(55%).Outcome was excellent in 19(95%). Complete recanalization was noted in 12(60%) and partial recanalization in 8(40%). No complications emerged out of the drug use. In clinically stable CVT rivaroxaban is safe and effective and may be used without previous heparin therapy. This can shorten the duration of hospitalization thereby decreasing the costs of treatment.

Shankar Iyer R ，Tcr R ，Akhtar S ，Muthukalathi K ，Kumar P ，Muthukumar K ... -  《-》

Direct Oral Anticoagulants for the Treatment of Cerebral Venous Thrombosis.

Cerebral venous thrombosis (CVT) is an uncommon neurological condition usually treated with heparin followed by oral vitamin K antagonists (VKAs). In patients with venous thromboembolism (VTE), compared to VKAs, direct oral anticoagulants (DOACs) offer several advantages. However, there is little data concerning their use in managing CVT. This retrospective observational study pursued 2 objectives: (1) to investigate clinical characteristics of CVT patients treated with heparin + DOACs vs. heparin + standard treatment; (2) to compare clinical outcomes. Consecutive CVT patients recruited from January 2016 to March 2018 in 2 French university hospitals (Lyon, Saint-Etienne), and treated with DOACs or VKAs were identified. Radiological evolution, VTE, hemorrhagic events, and antithrombotic medication were recorded. Functional outcome was assessed by the modified Rankin scale score and venous recanalization was assessed by magnetic resonance imaging. Overall, 41 patients were included: 25 (61%) received VKAs and 16 (39%) DOACs. We identified no clinical or radiological features explaining the physicians' preference for a specific anticoagulation treatment, and age, initial clinical presentation, radiological severity, and individual risk factors thus unlikely guided the choice of anticoagulant. No DOAC patient exhibited clinical or radiological thrombosis aggravation, and the thrombosis completely vanished in 6 (40%). Two of the VKA-treated patients (28.6%) demonstrated complete venous recanalization, whereas 3 others experienced clinical or radiological aggravation versus baseline. There was no major bleeding leading to hospitalization in both groups. The collected data on DOAC efficacy and safety in CVT management appear encouraging, yet needs to be confirmed by larger prospective randomized clinical trials.

Lurkin A ，Derex L ，Fambrini A ，Bertoletti L ，Epinat M ，Mismetti P ，Dargaud Y ... -  《-》

Non-Vitamin K Antagonist Oral Anticoagulants for the Treatment of Cerebral Venous Sinus Thrombosis: a Retrospective, Matched Cohort Analysis.

The management of cerebral venous sinus thrombosis (CVT) is a common problem facing vascular neurologists. American Heart Association/American Stroke Association guidelines suggest the use of heparin followed by vitamin K antagonists (VKAs) for anticoagulation in CVT. In recent years, the evidence base has solidified for the use of non-vitamin K antagonist oral anticoagulants (NOACs) in lower extremity deep vein thrombosis. Because data supporting their use in CVT are limited, with the strongest evidence comprising one randomized controlled trial of dabigatran, we sought to review our experience with NOACs in the treatment of CVT at a tertiary care center to address efficacy and safety. We retrospectively reviewed charts of all patients with CVT treated with an NOAC at our tertiary care facility in the years 2011-2019. We collected data on demographics, risk factors for CVT, clinical features at presentation, imaging results, anticoagulation regimen, bleeding complications, and disability at follow-up. We compared disability at follow-up and major hemorrhagic events with age-matched and sex-matched controls treated with VKAs over the same time period and with historical controls. We identified 29 patients with CVT treated with an NOAC, 27 of whom had follow-up within our system. NOACs that were used for treatment included apixaban (20 patients), rivaroxaban (6 patients) and dabigatran (1 patient). NOAC use was associated with stabilization of a clot or partial recanalization in 55.6% of patients and complete recanalization in 14.8% at a median follow-up time of 6 months. The median modified Rankin Score (mRS) at follow-up was 0, with one death. Three patients (11.1%) had major bleeding complications, including two with symptomatic worsening of intracranial hemorrhage. Comparisons of 27 age-matched and sex-matched controls treated with VKAs showed no significant differences in terms of partial recanalization (55.6% vs. 63.0%, p = 0.29), complete recanalization (14.8% vs. 25.9%, p = 0.73), mRS at follow-up (median 0 vs. 0, p = 0.23), or major bleeding (11.1% vs. 11.1%, p > 0.99). Comparisons with the historical International Study on Cerebral Vein and Dural Sinus Thrombosis cohort showed similar functional outcomes: 92.6% of patients treated with NOACs and 88.9% of patients treated with VKAs at the Washington University School of Medicine in St. Louis, as well as 86.2% of patients treated with VKAs in the historical study cohort, had mRS of 0-2 at follow-up (p = 0.60). Rates of major bleeding compared with this cohort were also similar (11.1% vs. 11.1% vs. 14.5%, p = 0.80). The safety and efficacy results of NOAC use for CVT were similar to those for age-matched and sex-matched controls treated with VKAs, as well as historical published controls. Assessment of NOAC efficacy and safety in CVT in multicenter cohort studies and randomized controlled trials is warranted.

Giles JA ，Balasetti VKS ，Zazulia AR 《-》

Treatment of proximal deep-vein thrombosis with the oral direct factor Xa inhibitor rivaroxaban (BAY 59-7939): the ODIXa-DVT (Oral Direct Factor Xa Inhibitor BAY 59-7939 in Patients With Acute Symptomatic Deep-Vein Thrombosis) study.

Agnelli G ，Gallus A ，Goldhaber SZ ，Haas S ，Huisman MV ，Hull RD ，Kakkar AK ，Misselwitz F ，Schellong S ，ODIXa-DVT Study Investigators ... -  《-》