Rivaroxaban for the treatment of symptomatic deep-vein thrombosis and pulmonary embolism in Chinese patients: a subgroup analysis of the EINSTEIN DVT and PE studies

Yuqi Wang,Ákos F Pap,Changwei Liu,Kejing Ying,Katharina Müller,Martin H Prins,Zhihong Liu,Zhong Chen,Anthonie Wa Lensing,Jiwei Zhang,Isabelle Ling Meng,Bi Jin,Chen Wang,Yuxia Shao,Zhicheng Jing

doi:10.1186/1477-9560-11-25

Abstract

BackgroundThe worldwide EINSTEIN DVT and EINSTEIN PE studies randomized 8282 patients with acute symptomatic deep-vein thrombosis (DVT) and/or pulmonary embolism (PE) and, for the first time in trials in this setting, included patients in China. This analysis evaluates the results of these studies in this subgroup of patients.MethodsA total of 439 Chinese patients who had acute symptomatic DVT (n=211), or PE with or without DVT (n=228), were randomized to receive rivaroxaban (15 mg twice daily for 21 days, followed by 20 mg once daily) or standard therapy of enoxaparin overlapping with and followed by an adjusted-dose vitamin K antagonist, for 3, 6, or 12 months. The primary efficacy outcome was symptomatic recurrent venous thromboembolism. The principal safety outcome was major or non-major clinically relevant bleeding.ResultsThe primary efficacy outcome occurred in seven (3.2%) of the 220 patients in the rivaroxaban group and in seven (3.2%) of the 219 patients in the standard-therapy group (hazard ratio, 1.04; 95% confidence interval 0.36–3.0; p=0.94). The principal safety outcome occurred in 13 (5.9%) patients in the rivaroxaban group and in 20 (9.2%) patients in the standard-therapy group (hazard ratio, 0.63; 95% confidence interval 0.31–1.26; p=0.19). Major bleeding was observed in no patients in the rivaroxaban group and in five (2.3%) patients in the standard-therapy group. In fragile patients (defined as age >75 years, creatinine clearance <50 mL/min, and/or body weight ≤50 kg), the principal safety outcome occurred in four (8.9%) of the 45 patients who received rivaroxaban compared with seven (15.2%) of the 46 patients who received standard therapy.ConclusionsIn Chinese patients with acute symptomatic DVT and/or PE, rivaroxaban was as efficacious as enoxaparin followed by vitamin K antagonist therapy, with a similar safety profile. The relative efficacy and safety of rivaroxaban compared with enoxaparin/vitamin K antagonist were consistent with that found in the rest of the world.Trial registration numberEINSTEIN PE, ClinicalTrials.gov NCT00439777; EINSTEIN DVT, ClinicalTrials.gov NCT00440193

Highlights

The worldwide EINSTEIN DVT and EINSTEIN PE studies randomized 8282 patients with acute symptomatic deep-vein thrombosis (DVT) and/or pulmonary embolism (PE) and, for the first time in trials in this setting, included patients in China
Patients were ineligible to participate if they had received a therapeutic dose of parenteral anticoagulant for more than 48 hours or if they had received more than a single dose of a vitamin K antagonist (VKA) before randomization; if thrombectomy had been performed, a vena cava filter placed, or a fibrinolytic agent administered for treatment of the current episode; or if they had any contraindication listed in the local labeling of enoxaparin, warfarin, or acenocoumarol
Because the metabolism of rivaroxaban is mediated by cytochrome P450 3A4 (CYP3A4), CYP3A4 inhibitors can decrease the metabolism of rivaroxaban, causing an increase in the area under the plasma concentration–time curve (AUC) and the maximum plasma concentration (Cmax); CYP3A4 inducers can increase the metabolism of rivaroxaban, decreasing the AUC and Cmax

Summary

Introduction

The worldwide EINSTEIN DVT and EINSTEIN PE studies randomized 8282 patients with acute symptomatic deep-vein thrombosis (DVT) and/or pulmonary embolism (PE) and, for the first time in trials in this setting, included patients in China. This analysis evaluates the results of these studies in this subgroup of patients. The results of VTE treatment among Chinese nationals are not well documented, there seems to be a general belief that the risk of bleeding is high among patients receiving standard treatment, and that vitamin K antagonist (VKA) therapy should be dosed carefully with a tendency towards lower international normalized ratio (INR) values. Similar concerns about bleeding would apply to the direct oral anticoagulants

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