Effectiveness and safety of rivaroxaban versus warfarin in patients with unprovoked venous thromboembolism: A propensity-score weighted administrative claims cohort study.

In phase III trials, rivaroxaban demonstrated non-inferiority over enoxaparin/warfarin to prevent recurrent venous thromboembolism (VTE), with a reduction of major bleeding. However, compared to provoked VTE, the risk-benefit ratio of rivaroxaban may be different for patients with unprovoked VTE. In a retrospective claims data analysis using US MarketScan claims from 1/2012 to 12/2016, we included adults with a primary diagnosis of VTE newly-initiated on rivaroxaban or warfarin within 30-days of the incident VTE and with ≥12-months of continuous insurance benefits prior to the VTE (baseline). Patients with provoked VTE, a claim for anticoagulation during baseline or who redeemed prescriptions for ≥1 oral anticoagulant were excluded. Our primary outcomes were recurrent VTE and major bleeding at 6-months using an intention-to-treat (ITT) analysis. Three-month ITT and 12-month on-treatment (30-day permissible gap) analyses were also performed. Inverse probability-of-treatment weights based on propensity-scores and Cox regression were used to compare outcomes. We identified 10,489 rivaroxaban users and 26,364 warfarin users with incident unprovoked VTE. At 6-months, rivaroxaban was associated with a hazard ratio (HR) of 0.60 (95% confidence interval [CI] = 0.54-0.67) for recurrent VTE (number-needed-to-treat: 59; 95%CI 49-76) and a HR = 0.80 (95% CI = 0.66-0.98) for major bleeding versus warfarin. Our findings remained consistent in the 3- and 12-month analyses. Consistent with the results from the EINSTEIN phase-III trials, findings of our routine practice study suggest that, in patients with unprovoked VTE, rivaroxaban has the potential to reduce both the risk of major bleeding and recurrent VTE compared to warfarin.

Coleman CI ，Peacock WF ，Bunz TJ ，Beyer-Westendorf J ... -  《-》

Effectiveness and safety of rivaroxaban versus warfarin for treatment and prevention of recurrence of venous thromboembolism.

Coleman CI ，Bunz TJ ，Turpie AGG 《-》

Effectiveness and safety of rivaroxaban versus warfarin in patients with provoked venous thromboembolism.

Coleman CI ，Turpie AGG ，Bunz TJ ，Beyer-Westendorf J ... -  《-》

Effectiveness and safety of rivaroxaban and warfarin in patients with unprovoked venous thromboembolism: a propensity-matched nationwide cohort study.

Deep vein thrombosis (DVT) and pulmonary embolism are collectively known as venous thromboembolism (VTE), which is a common vascular disease and a major cause of morbidity and mortality worldwide. We compare effectiveness and safety of rivaroxaban versus warfarin in a prospective cohort of routine care patients with incident unprovoked VTE. In this propensity-matched cohort study, we linked nationwide Danish health registries to identify all patients with a first hospital diagnosis of unprovoked VTE who were new users of rivaroxaban or warfarin. Excluded patients included those who had not been residents in Denmark for at least 1 year before VTE diagnosis, patients with outpatient VTE diagnosis only, patients with other indications for oral anticoagulation treatment, patients with previous experience of oral anticoagulation, patients who did not have a prescription for rivaroxaban or warfarin within 7 days of VTE, and patients who redeemed prescriptions for both rivaroxaban and warfarin, or other oral anticoagulants. Primary effectiveness outcome was recurrent VTE and primary safety outcome was major bleeding. We used propensity matching and Cox regression to compare rates of the outcomes with rivaroxaban versus standard treatment. From Dec 9, 2011, to Feb 28, 2016, we identified 29 963 patients with incident VTE. After exclusion, we identified 1734 propensity-matched patients given rivaroxaban (1751 before propensity matching) and 2945 propensity-matched patients given warfarin. The rate of recurrent VTE at 6 months' follow-up was 9·9 incidents per 100 person-years with rivaroxaban versus 13·1 incidents per 100 person-years with warfarin, yielding a hazard ratio (HR) of 0·74 (95% CI 0·56-0·96). The rate of major bleeding was 2·4 per 100 person-years at 6 months in rivaroxaban users versus 2·0 in warfarin users (HR 1·19, 95% CI 0·66-2·13). In this clinical practice setting, rivaroxaban in patients with unprovoked VTE was associated with reduced risk of recurrent VTE compared with standard treatment, without compromising safety. Obel Family Foundation.

Larsen TB ，Skjøth F ，Kjældgaard JN ，Lip GYH ，Nielsen PB ，Søgaard M ... -  《Lancet Haematology》

Comparative risk of major bleeding with rivaroxaban and warfarin: Population-based cohort study of unprovoked venous thromboembolism.

To assess the association between rivaroxaban and warfarin and major bleeding risk in unprovoked venous thromboembolism (VTE) patients. Using US MarketScan claims from 1/2012-12/2016, we identified patients who had ≥1 primary hospitalization/emergency department visit diagnosis code for an unprovoked VTE, newly initiated on rivaroxaban or warfarin within 30 days after the VTE and ≥12 months of insurance coverage prior to the VTE. Differences in baseline covariates were adjusted using inverse-probability-of-treatment weights based on propensity scores (residual absolute standardized differences <0.1 achieved for all covariates). Endpoints included any major, gastrointestinal, genitourinary, intracranial, and other bleeds. Patients were followed for up to 12 months or until endpoint occurrence, index oral anticoagulant discontinuation/switch, insurance disenrollment or end of follow-up. We identified 10 489 rivaroxaban and 26 364 warfarin patients with an unprovoked VTE. Upon Cox regression, rivaroxaban reduced patients' hazard of major bleeding by 27% (95% confidence interval [CI] = 8%-42%), gastrointestinal bleeding by 38% (95% CI = 14%-55%), and intracranial hemorrhage by 81% (95% CI = 41%-99%) vs warfarin. No subtype of major bleeding occurred statistically more often in rivaroxaban vs warfarin-treated patients. Rivaroxaban was associated with a reduced risk of overall, gastrointestinal, and intracranial major bleeding vs warfarin in unprovoked VTE. No bleeding subtype was significantly more frequent in rivaroxaban patients.

Kohn CG ，Bunz TJ ，Beyer-Westendorf J ，Coleman CI ... -  《-》