Real-World Analysis Confirms Rivaroxaban Reduces Risk of VTE and Major Bleeding, Compared With Warfarin

Previously, a series of phase III trials from EINSTEIN investigators determined that the direct oral anticoagulant (DOAC) rivaroxaban is non-inferior to enoxaparin and warfarin for the prevention of recurrent venous thromboembolism (VTE) and was associated with a 46 percent decreased risk of major bleeding (p=0.002). To assess the safety and efficacy of rivaroxaban in a “real-world” population, Craig I. Coleman, PharmD, from the University of Connecticut School of Pharmacy, and co-authors analyzed a large administrative claims database, finding that, similar to what the EINSTEIN investigators reported, rivaroxaban “appears to reduce patients’ hazard of both recurrent VTE and major bleeding in routine practice.”

“That our analysis’ findings are relatively consistent with those of the EINSTEIN clinical trial program should provide an extra layer of reassurance to clinicians when prescribing rivaroxaban for acute VTE,” the authors wrote in their report, which was published in Thrombosis and Haemostasis.

The researchers retrospectively analyzed the Truven Health MarketScan® claims database to identify adult patients who were diagnosed with deep-vein thrombosis or pulmonary embolism (PE) during a hospitalization or visit to an emergency department between January 2012 and June 2015. Patients were included in the analysis if they were newly initiated on rivaroxaban (n=13,609; 43.2% were ≥60 years old) or warfarin (n=32,244; 42.5% were ≥60 years old) within 30 days after the index event and had ≥180 days of continuous medical and prescription benefits prior to the index event (baseline). Patients with a VTE claim or prescription claim for an anticoagulant at baseline were excluded.

Patients were followed for a maximum of 12 months or until VTE recurrence or major bleeding, switch or discontinuation of index oral anticoagulation, or insurance-plan disenrollment. Compared with those who received warfarin, patients who received rivaroxaban tended to be younger and have fewer comorbidities, particularly hypertension, diabetes, cancer, coagulopathies, and chronic kidney disease.

Rivaroxaban was associated with a 19 percent reduction in recurrent VTE and a 21 percent reduction in major bleeding hazards, as well as decreased hazards of intracranial hemorrhage and gastrointestinal bleeding compared with patients treated with warfarin (see TABLE 5). In multivariable analysis controlling for patient demographics, comorbidities, known VTE risk factors, and concomitant medications at baseline, these risk reductions were “relatively consistent across subgroups,” the authors noted, including by sex, age, obesity, presence of PE, and history of or active cancer (see TABLE 6).

“Our results were also robust to changes in study methodology,” the researchers added. When they conducted a sensitivity analysis by removing the 12-month cap on follow-up, rivaroxaban’s observed effectiveness and safety were confirmed, with an 18 percent reduction in the risk of recurrent VTE (hazard ratio [HR] = 0.82; 95% CI 0.74-0.90; p value not provided) and a 23 percent reduction in the risk of major bleeding (HR=0.77; 95% CI 0.64-0.93; p value not provided) compared with patients treated with warfarin.

“An interesting finding of our analysis was the relatively high proportion of cancer patients (15.8%) receiving rivaroxaban for treatment of their VTE,” the authors noted. In comparison, only 5.6 percent of patients in the EINSTEIN clinical trials received rivaroxaban. Although U.S. and European clinical guidelines do not recommend rivaroxaban and other DOACs for cancer-associated thrombosis, “our data suggest that some patients do receive rivaroxaban in the setting of cancer-associated thrombosis, perhaps because of its convenience of administration compared to low-molecular-weight heparin.”

The study is limited by its retrospective, claims-based design (which may introduce selection and misclassification biases), as well confounding factors that were not identifiable.

Contributing authors report financial relationships with Bayer, Janssen, Boehringer Ingelheim, Astellas, Portola, and Takeda.


Coleman CI, Bunz TJ, Turpie AGG. Effectiveness and safety of rivaroxaban versus warfarin for treatment and prevention of recurrence of venous thromboembolism. Thromb Haemost. 2017 June 22. [Epub ahead of print]