Oral rivaroxaban for Japanese patients with symptomatic venous thromboembolism – the J-EINSTEIN DVT and PE program

Abstract

BackgroundThe global EINSTEIN DVT and PE studies compared rivaroxaban (15 mg twice daily for 3 weeks followed by 20 mg once daily) with enoxaparin/vitamin K antagonist therapy and demonstrated non-inferiority for efficacy and superiority for major bleeding. Owing to differences in targeted anticoagulant intensities in Japan, Japanese patients were not enrolled into the global studies. Instead, a separate study of deep vein thrombosis (DVT) and/or pulmonary embolism (PE) in Japanese patients was conducted, which compared the Japanese standard of care with a reduced dose of rivaroxaban.MethodsWe conducted an open-label, randomized trial that compared 3, 6, or 12 months of oral rivaroxaban alone (10 mg twice daily or 15 mg twice daily for 3 weeks followed by 15 mg once daily) with activated partial thromboplastin time-adjusted intravenous unfractionated heparin (UFH) followed by warfarin (target international normalized ratio 2.0; range 1.5–2.5) in patients with acute, objectively confirmed symptomatic DVT and/or PE. Patients were assessed for the occurrence of symptomatic recurrent venous thromboembolic events or asymptomatic deterioration and bleeding.ResultsEighty-one patients were assigned to rivaroxaban and 19 patients to UFH/warfarin. Three patients were excluded because of serious non-compliance issues. The composite of symptomatic venous thromboembolic events or asymptomatic deterioration occurred in 1 (1.4%) rivaroxaban patient and in 1 (5.3%) UFH/warfarin patient (absolute risk difference, 3.9% [95% confidence interval, -3.4–23.8]). No major bleeding occurred during study treatment. Clinically relevant non-major bleeding occurred in 6 (7.8%) patients in the rivaroxaban group and 1 (5.3%) patient in the UFH/warfarin group.ConclusionsThe findings of this study in Japanese patients with acute DVT and/or PE suggest a similar efficacy and safety profile with rivaroxaban and control treatment, consistent with that of the worldwide EINSTEIN DVT and PE program.Trial registrationClinicaltrials.gov: NCT01516840 and NCT01516814.Electronic supplementary materialThe online version of this article (doi:10.1186/s12959-015-0035-3) contains supplementary material, which is available to authorized users.

Análise do grau de recanalização da trombose venosa profunda: estudo comparativo de pacientes tratados com varfarina versus rivaroxabana

“…At the end of the treatment, 62% of the patients in the rivaroxaban group and 31.6% in the UFH+VKA group exhibited normalization on examinations. 22 In our study, examinations of patients after 30 days of treatment revealed partial or total recanalization rates of 10% and 55.3% in Groups I (heparin + warfarin) and II (rivaroxaban), respectively. At the end of the J-EINSTEIN-DVT/PE study, 95.8% of the patients in the rivaroxaban group exhibited improvement or normalization on examinations, compared to 89.5% of patients treated with UFH+VKA.…”

Mortality outcomes in patients receiving direct oral anticoagulants: a systematic review and meta‐analysis of randomized controlled trials

“…Of these 13 trials, eight were classified as high quality based on rigorous randomization, allocation concealment, blinding and outcome reporting without potential bias. There were four studies at high risk of bias due to their open‐label design (EINSTEIN‐DVT , EINSTEIN‐PE , J‐EINSTEIN‐DVT/PE and RE‐LY ). One study did not report the method used to generate the randomization sequence and allocation concealment, and the risk of bias was judged as unclear.…”

“…Thirteen phase III RCTs were included in qualitative and quantitative synthesis. The trials investigated dabigatran (n = 4 [15][16][17][18]), rivaroxaban (n = 5 [19][20][21][22][23]), apixaban (n = 2 [24,25]) and edoxaban (n = 2 [26,27]). Across the 13 trials, 58 021 patients were randomly assigned to receive DOAC and 44 822 to receive warfarin (or heparin/low-molecular-weight heparin, followed by warfarin).…”

Overview of Current Evidence on the Impact of the Initial High Dose of the Direct Factor Xa Inhibitor Rivaroxaban on Thrombus Resolution in the Treatment of Venous Thromboembolism

“…The J-EINSTEIN DVT and PE program assessed the effectiveness of rivaroxaban compared with standard therapy in 100 consecutive Japanese patients with objectively confirmed proximal DVT and/or PE. 40) This open-label, randomized, multicenter trial showed that neither rivaroxaban (15 or 10 mg bid for 21 days followed by 15 mg once-daily) nor standard therapy (UFH/warfarin) caused any major bleeding events. On day 22 of treatment, repeat imaging showed the complete absence of thrombi in 26.7% of rivaroxaban patients compared with 15.8% of those treated with standard therapy, but the results were not statistically significant owing to patient numbers.…”

“…On day 22 of treatment, repeat imaging showed the complete absence of thrombi in 26.7% of rivaroxaban patients compared with 15.8% of those treated with standard therapy, but the results were not statistically significant owing to patient numbers. 40) Additional subanalyses of the phase III EINSTEIN datasets have enhanced our understanding of the early effects of high-dose NOAC treatment on thrombus resolution in patients with PE. A predefined safety analysis of PE thrombus resolution in an initial cohort of patients in the EINSTEIN PE study showed a reduction in vascular obstruction.…”