Safety and Efficacy of Dabigatran Etexilate vs Dose-Adjusted Warfarin in Patients With Cerebral Venous Thrombosis

Abstract

for the RE-SPECT CVT Study Group IMPORTANCE Patients with cerebral venous thrombosis (CVT) are at risk of recurrent venous thrombotic events (VTEs). Non-vitamin K oral anticoagulants have not been evaluated in randomized controlled trials in CVT.OBJECTIVE To compare the efficacy and safety of dabigatran etexilate with those of dose-adjusted warfarin in preventing recurrent VTEs in patients who have experienced a CVT. DESIGN, SETTING, AND PARTICIPANTS RE-SPECT CVT is an exploratory, prospective, randomized (1:1), parallel-group, open-label, multicenter clinical trial with blinded end-point adjudication (PROBE design). It was performed from December 21, 2016, to June 22, 2018, with a follow-up of 25 weeks, at 51 tertiary sites in 9 countries (). Adult consecutive patients with acute CVT, who were stable after 5 to 15 days of treatment with parenteral heparin, were screened for eligibility. Patients with CVT associated with central nervous system infection or major trauma were excluded, but those with intracranial hemorrhage from index CVT were allowed to participate. After exclusions, 120 patients were randomized. Data were analyzed following the intention-to-treat approach.INTERVENTIONS Dabigatran, 150 mg twice daily, or dose-adjusted warfarin for a treatment period of 24 weeks. MAIN OUTCOMES AND MEASURES Primary outcome was a composite of patients with a new VTE (recurrent CVT, deep vein thrombosis of any limb, pulmonary embolism, and splanchnic vein thrombosis) or major bleeding during the study period. Secondary outcomes were cerebral venous recanalization and clinically relevant non-major bleeding events. RESULTSIn total, 120 patients with CVT were randomized to the 2 treatment groups (60 to dabigatran and 60 to dose-adjusted warfarin). Of the randomized patients, the mean (SD) age was 45.2 (13.8) years, and 66 (55.0%) were women. The mean (SD) duration of exposure was 22.3 (6.16) weeks for the dabigatran group and 23.0 (5.20) weeks for the warfarin group. No recurrent VTEs were observed. One (1.7%; 95% CI, 0.0-8.9) major bleeding event (intestinal) was recorded in the dabigatran group, and 2 (3.3%; 95% CI, 0.4-11.5) (intracranial) in the warfarin group. One additional patient (1.7; 95% CI, 0.0-8.9) in the warfarin group experienced a clinically relevant non-major bleeding event. Recanalization occurred in 33 patients in the dabigatran group (60.0%; 95% CI, 45.9-73.0) and in 35 patients in the warfarin group (67.3%; 95% CI, 52.9-79.7). CONCLUSIONS AND RELEVANCEThis trial found that patients who had CVT anticoagulated with either dabigatran or warfarin had low risk of recurrent VTEs, and the risk of bleeding was similar with both medications, suggesting that both dabigatran and warfarin may be safe and effective for preventing recurrent VTEs in patients with CVT. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT02913326

Cerebral and Splanchnic Vein Thrombosis: Advances, Challenges, and Unanswered Questions

“…They were mainly small observational studies, either retrospective [36][37][38][39][40] or prospective [41][42][43], and there was only one RCT [44]. The number of patients treated with DOAC ranged from 6 [38] to 60 [44] patients. The average anticoagulant treatment duration ranged from 5 [44] to 12 [40] months.…”

“…The number of patients treated with DOAC ranged from 6 [38] to 60 [44] patients. The average anticoagulant treatment duration ranged from 5 [44] to 12 [40] months. Three studies evaluated rivaroxaban [36,38,41], two dabigatran [37,44], and three cohorts included different DOACs [40,42,43].…”

“…Three studies evaluated rivaroxaban [36,38,41], two dabigatran [37,44], and three cohorts included different DOACs [40,42,43]. In the majority of the studies, the DOAC were used after an initial treatment with UFH or LMWH [36,37,40,42,44] in order to achieve stable conditions. There was only one study enrolling 20 patients who started directly with rivaroxaban 15 mg twice daily (BID) for 3 weeks, followed by 20 mg once daily (OD) [41].…”

“…Sinus Thrombosis) randomized 120 CVT patients to either dabigatran 150 mg BID or dose-adjusted warfarin (INR target range 2.0-3.0) after an initial parenteral treatment with either UFH or LMWH for 5-15 days [44]. However, patients with central nervous system infections, major head trauma, active cancer, or coma were excluded from this trial [44].…”

Pädiatrische ausgedehnte zerebrale Sinusvenenthrombose mit benignem Verlauf

“…Der Einsatz von oralen direkten Thrombin-oder Faktor-Xa-Inhibitoren wird in der gelten-den DGN-Leitlinien für Erwachsene aufgrund nicht ausreichender wissenschaftlicher Daten nicht empfohlen [10]. Die nach Erstellung dieser Leitlinie 2019 publizierte RE-SPECT-CVT-Studie zeigte bei der Behandlung von Erwachsenen mit CVST für Dabigatran ein ähnlich gutes Sicherheitsprofil und Effektivität zur Vermeidung wiederholter venothrombotischer Ereignisse wie Warfarin [11]. Die endovaskuläre rekanalisierende Therapie wird auch bei Kindern nur für ausgeprägte, therapierefraktäre Fälle vorbehalten [12].…”