Elena Zapata-Arriaza, MD
Ferro JM, Coutinho JM, Dentali F, Kobayashi A, Alasheev A, Canhão P, et al. Safety and Efficacy of Dabigatran Etexilate vs Dose-Adjusted Warfarin in Patients With Cerebral Venous Thrombosis: A Randomized Clinical Trial. JAMA Neurol. 2019.
Cerebral venous thrombosis (CVT) survivors are exposed to an increased risk of recurrent venous thrombotic events (VTEs) in cerebral venous sinuses, limbs, and splanchnic veins, or pulmonary embolism. Current practice recommendations for preventing VTE recurrence after CVT is anticoagulation using vitamin K antagonists for variable periods. Direct non–vitamin K oral anticoagulants, like dabigatran, as an alternative to warfarin treatment, have shown increased but insufficient evidence for CVT management. In order to evaluate the efficacy and safety of dabigatran compared with dose-adjusted warfarin in the prevention of recurrent VTE and CVT, the authors performed an exploratory, multicenter PROBE design clinical trial (the RE-SPECT CVT trial).
CVT confirmation had to be done with magnetic resonance imaging (MRI) plus MR venography, computed tomography (CT) plus CT venography, or intraarterial venography. Patients should have achieved clinical stability after receiving acute CVT treatment as required. Among major exclusion criteria were found the inability to swallow oral medication, CVT associated with central nervous system infection or major head trauma, planned surgical procedure for CVT life-threatening or major bleeding in the previous 6 months, need to continue previous treatment with an anticoagulant for an indication other than CVT, current or recent (<6months) malignancy, and creatinine clearance level less than30mL/min. Patients were randomized to receive either dabigatran (150 mg twice daily) or warfarin (dose adjusted to maintain an international normalized ratio [INR] between 2.0 and 3.0).
Finally, 120 patients with CVT were randomized to the 2 treatment groups (60 to dabigatran and 60 to dose-adjusted warfarin). The authors found no recurrent VTE during the RE-SPECT CVT trial. In addition, the authors have shown that anticoagulant therapy for 6 months with either dabigatran or dose-adjusted warfarin was associated with few major or clinically relevant bleeding events, new intracranial hemorrhages, or enlargement of baseline hemorrhagic lesions. All these results were obtained under excellent adherence rates in the dabigatran group, and good therapeutic range time (>65%) for patients in the warfarin group.
These results are encouraging, in terms of expanding therapeutic options in cerebral venous thrombosis. It would allow us the employment of a drug (dabigatran) that does not require such close controls for its proper functioning in a working-age population. Likewise, the spectrum of interactions with food and other medicines of dabigatran is lower, although the dropouts in this group were mostly due to digestive intolerance. However, the limitations of the study, such as the short follow-up time, which affects the low recurrence rates, or the exclusion of groups of patients at high risk of new cerebral thrombosis (active cancer), should make us take these results with optimism and realism at the same time. This study is a very interesting starting point, which needs to broaden the selection to patients with thrombophilias or prolong follow-up times to increase the candidate patients for this therapeutic alternative.