Safety and Efficacy of Dabigatran Etexilate vs Dose-Adjusted Warfarin in Patients With Cerebral Venous Thrombosis A Randomized Clinical Trial
JAMA Neurol. 2019-12-01; 76(12): 1457
DOI: 10.1001/JAMANEUROL.2019.2764
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1. JAMA Neurol. 2019 Dec 1;76(12):1457-1465. doi: 10.1001/jamaneurol.2019.2764.
Safety and Efficacy of Dabigatran Etexilate vs Dose-Adjusted Warfarin in Patients
With Cerebral Venous Thrombosis: A Randomized Clinical Trial.
Ferro JM(1)(2), Coutinho JM(3), Dentali F(4), Kobayashi A(5)(6), Alasheev A(7),
Canhão P(1), Karpov D(8), Nagel S(9), Posthuma L(3), Roriz JM(10), Caria J(11),
Frässdorf M(12), Huisman H(13), Reilly P(14), Diener HC(15); RE-SPECT CVT Study
Group.
Author information:
(1)Department of Neurosciences and Mental Health, Serviço de Neurologia, Hospital
Santa Maria/Centro Hospitalar Lisboa Norte, Lisbon, Portugal.
(2)Instituto de Medicina Molecular and Faculdade de Medicina, Universidade de
Lisboa, Lisbon, Portugal.
(3)Department of Neurology, Academic Medical Centre, Amsterdam, the Netherlands.
(4)Department of Clinical and Experimental Medicine, Insubria University, Varese,
Italy.
(5)Faculty of Health Sciences and Physical Education, Kazimierz Pulaski
University of Technology and Humanities Radom, Warsaw, Poland.
(6)Interventional Stroke and Cerebrovascular Disease Treatment Center, Institute
of Psychiatry and Neurology, Warsaw, Poland.
(7)Sverdlovsk Regional Clinical Hospital No 1, Yekaterinburg, Russia.
(8)Neurology Department, Regional State Budget Healthcare, City Hospital No. 5,
Barnaul, Russia.
(9)Department of Neurology, University Hospital Heidelberg, Heidelberg, Germany.
(10)Neurology Department, Centro Hospitalar de Entre o Douro e Vouga, Santa Maria
da Feira, Portugal.
(11)Boehringer Ingelheim International, Ingelheim am Rhein, Germany.
(12)Boehringer Ingelheim Pharma GmbH & Co KG, Ingelheim am Rhein, Germany.
(13)Boehringer Ingelheim BV, Alkmaar, the Netherlands.
(14)Department of Clinical Development, Boehringer Ingelheim Pharmaceuticals Inc,
Ridgefield, Connecticut.
(15)Faculty of Medicine, University Duisburg-Essen, Essen, Germany.
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 (France, Germany, India, Italy, the Netherlands, Poland, Portugal,
Russia, and Spain). 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.
Results: In 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 Relevance: This 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.
DOI: 10.1001/jamaneurol.2019.2764
PMCID: PMC6724157
PMID: 31479105 [Indexed for MEDLINE]