Healthcare resource use in XALIA: A subgroup analysis of a non-interventional study of rivaroxaban versus standard anticoagulation for deep vein thrombosis.

The non-interventional XALIA study compared the safety and effectiveness of rivaroxaban with standard anticoagulation for the treatment of venous thromboembolism in routine clinical practice. This substudy assessed the effect of treatment with rivaroxaban on healthcare resource use, hospital length of stay (LOS) and frequency of hospitalisation. In XALIA, patients aged ≥18 years scheduled to receive ≥3 months of rivaroxaban or standard anticoagulation treatment for deep vein thrombosis (DVT) were eligible. Treatment decisions were at the physician's discretion. Healthcare resource use, including hospital admission for the index DVT and initial LOS, was documented. The main analyses in this substudy were conducted in a 1:1 propensity score-matched set (PMS) of patients, with adjustment for cancer at baseline. In the PMS analysis, 1124 rivaroxaban-treated patients and 1124 standard anticoagulation-treated patients were included. Baseline characteristics were similar between groups (mean age 60.8 years vs. 61.2 years, DVT only rates of 89.7% vs. 90.2% and cancer rates of 8.4% vs. 8.5%, respectively). Of these, 433/1124 (38.5%) rivaroxaban-treated patients and 438/1124 (39.0%) standard anticoagulation-treated patients were hospitalised. Index event LOS in the PMS analysis was a least-squares mean of 2.6 days shorter with rivaroxaban vs. standard anticoagulation (5.4 vs. 8.0 days; geometric means ratio = 0.67 [95% confidence interval 0.61-0.74, P < 0.001]). In XALIA, hospital LOS was shorter with rivaroxaban than with standard anticoagulation, consistent with the phase III study results. DVT treatment with rivaroxaban in routine clinical practice may reduce the cost per patient vs. standard anticoagulation.

Mantovani LG ，Haas S ，Kreutz R ，Folkerts K ，Gebel M ，Monje D ，Schneider J ，van Eickels M ，Sahin K ，Zell E ，Ageno W ，Turpie AGG ... -  《-》

Safety and effectiveness of oral rivaroxaban versus standard anticoagulation for the treatment of symptomatic deep-vein thrombosis (XALIA): an international, prospective, non-interventional study.

The efficacy and safety of the anticoagulant rivaroxaban for the treatment and secondary prevention of deep-vein thrombosis and pulmonary embolism has been shown in phase 3 trials. However, data about rivaroxaban use in routine clinical practice are needed. XA inhibition with rivaroxaban for Long-term and Initial Anticoagulation in venous thromboembolism (XALIA) was a multicentre, international, prospective, non-interventional study of patients with deep-vein thrombosis, done in hospitals and community care centres in 21 countries. The study investigated the safety and effectiveness of rivaroxaban compared with standard anticoagulation therapy (initial treatment with unfractionated heparin, low-molecular-weight heparin, or fondaparinux, usually overlapping with and followed by a vitamin K antagonist) for at least 3 months. Eligible patients were adults (aged ≥18 years) with an objectively confirmed diagnosis of deep-vein thrombosis, and an indication to receive anticoagulation treatment for at least 3 months. Following approval of rivaroxaban for the pulmonary embolism indication, patients with deep-vein thrombosis and concomitant pulmonary embolism were also eligible; however, those with isolated pulmonary embolism were not included. Type, dose, and duration of therapy for each patient were at the physician's discretion. The primary effectiveness and safety outcomes were major bleeding, recurrent venous thromboembolism, and all-cause mortality. Propensity score-adjusted analyses were done to account for potential imbalances between groups. This study is registered with ClinicalTrials.gov, number NCT01619007. Between June 26, 2012, and March 31, 2014, 5142 patients were enrolled. The safety population (all patients who received at least one dose of the anticoagulant of interest) comprised 2619 patients in the rivaroxaban group and 2149 in the standard anticoagulant therapy group. Patients in the rivaroxaban group were younger and fewer had active cancer or concomitant pulmonary embolism than those in the standard anticoagulation group. In the propensity score-adjusted population, the frequency of major bleeding was 0·8% (19/2505) in the rivaroxaban group and 2·1% (43/2010) in the standard anticoagulation group, with a propensity score-adjusted hazard ratio (HR) of 0·77 (95% CI 0·40-1·50); p=0·44. The frequency of recurrent venous thromboembolism was 1·4% (36/2505) in the rivaroxaban group and 2·3% (47/2010) in the standard anticoagulation group (propensity score-adjusted HR 0·91 [95% CI 0·54-1·54], p=0·72). The all-cause mortality frequency was 0·4% (11/2505) in the rivaroxaban group and 3·4% (69/2010) in the standard anticoagulation group (propensity score-adjusted HR 0·51 [95% CI 0·24-1·07], p=0·074). The incidence of treatment-emergent adverse events in the safety population was similar between the two groups (944 [36·0%] of 2619 in the rivaroxaban group vs 805 [37·5%] of 2149 in the standard anticoagulation group). In routine clinical practice, rivaroxaban-treated patients had a lower risk profile at baseline than those treated with standard anticoagulation. Propensity score-adjusted results confirm that rivaroxaban is a safe and effective alternative to standard anticoagulation therapy in a broad range of patients. Rates of major bleeding and recurrent venous thromboembolism were low in rivaroxaban-treated patients and consistent with phase 3 findings. Bayer HealthCare Pharmaceuticals and Janssen Research & Development, LLC.

Ageno W ，Mantovani LG ，Haas S ，Kreutz R ，Monje D ，Schneider J ，van Eickels M ，Gebel M ，Zell E ，Turpie AG ... -  《Lancet Haematology》

XALIA-LEA: An observational study of venous thromboembolism treatment with rivaroxaban and standard anticoagulation in the Asia-Pacific, Eastern Europe, the Middle East, Africa and Latin America.

The prospective, non-interventional XALIA study investigated the safety and effectiveness of rivaroxaban and standard anticoagulation for the treatment of deep vein thrombosis (DVT). XALIA-LEA was conducted in regions not included in XALIA (Latin America, Eastern Europe, the Middle East, Africa, and the Asia-Pacific), and enrolled patients with isolated pulmonary embolism (PE). Adult patients with acute venous thromboembolism (VTE) indicated for ≥3 months' anticoagulant treatment were eligible; treatment strategies were at the physician's discretion. Patients receiving rivaroxaban or standard anticoagulation (unfractionated or low-molecular weight heparin/fondaparinux alone or overlapping with and followed by a vitamin K antagonist [VKA]) were included in the safety analysis. "Early switchers" to rivaroxaban (i.e. after receiving heparin/fondaparinux for >2-14 days and/or a VKA for 1-14 days) were not included in the safety analysis set. Of the 1972 eligible patients, 1285 received rivaroxaban, 402 received standard anticoagulation, and 285 were early switchers. Most patients who received rivaroxaban were appropriately selected, received the correct dosing schedule, reported few adverse effects. Outcomes were similar to previously published results, with rivaroxaban associated with a low rate of major bleeding (1.6%), recurrent VTE (1.4%) and all-cause mortality (2.3%). Including early switchers, relatively fewer patients with index isolated PE received rivaroxaban (14.4%) versus standard anticoagulation therapy (20.9%). Some regional variations and differences in outcomes by VTE subtype were apparent with standard anticoagulation treatment. XALIA-LEA reaffirms the safety and effectiveness of rivaroxaban for VTE treatment for countries not included in XALIA.

Kreutz R ，Mantovani LG ，Haas S ，Monje D ，Schneider J ，Bugge JP ，Gebel M ，Tamm M ，Ageno W ，Turpie AGG ... -  《-》

Analysis of patients with deep vein thrombosis switched from standard therapy to rivaroxaban in the non-interventional XALIA study.

XALIA assessed the safety and effectiveness of rivaroxaban for deep vein thrombosis (DVT) treatment in routine clinical practice. This substudy describes the clinical characteristics and outcomes of 'early switchers' - patients who received heparin or fondaparinux for >2-14days and/or a vitamin K antagonist (VKA) for 1-14days before switching to rivaroxaban. Patients with DVT (latterly with concomitant pulmonary embolism) received rivaroxaban or standard anticoagulation (initial treatment with heparin or fondaparinux, usually overlapping with and followed by a VKA). Patients administered rivaroxaban alone, or heparin or fondaparinux for ≤48h pre-enrollment were included in the rivaroxaban cohort. Therapy type, dose, and duration were at the physician's discretion. Primary outcomes were major bleeding, recurrent venous thromboembolism (VTE), and all-cause mortality. In 368 early switchers, recurrence or bleeding risk factors were more prevalent versus the rivaroxaban cohort, including creatinine clearance<50mL/min (6.5% vs. 3.9%), previous major bleeding (4.6% vs. 1.4%), active cancer (8.2% vs. 5.6%), and concomitant pulmonary embolism (20.9% vs. 8.4%). Crude incidence rates were numerically higher versus the rivaroxaban cohort for major bleeding (1.4% vs. 0.7%), recurrent VTE (2.2% vs. 1.4%), and all-cause mortality (0.8% vs. 0.5%). Patients who switched to rivaroxaban early in the treatment process had a higher frequency of risk factors for bleeding and recurrent VTE than patients treated with rivaroxaban; reflected by the higher risk of adverse events in that group during follow-up.

Turpie AGG ，Mantovani LG ，Haas S ，Kreutz R ，Monje D ，Schneider J ，van Eickels M ，Gebel M ，Ageno W ... -  《-》

Shorter Hospital Stays and Lower Costs for Rivaroxaban Compared With Warfarin for Venous Thrombosis Admissions.

Venous thromboembolism, including deep vein thrombosis and pulmonary embolism, results in a substantial healthcare system burden. This retrospective observational study compared hospital length of stay (LOS) and hospitalization costs for patients with venous thromboembolism treated with rivaroxaban versus those treated with warfarin. Hospitalizations for adult patients with a primary diagnosis of deep vein thrombosis or pulmonary embolism who were initiated on rivaroxaban or warfarin were selected from MarketScan's Hospital Drug Database between November 1, 2012, and December 31, 2013. Patients treated with warfarin were matched 1:1 to patients treated with rivaroxaban using exact and propensity score matching. Hospital LOS, time from first dose to discharge, and hospitalization costs were reported descriptively and with generalized linear models (GLMs). The final study cohorts each included 1223 patients (751 with pulmonary embolism and 472 with deep vein thrombosis). Cohorts were well matched for demographic and clinical characteristics. Mean (±SD) LOS was 3.7±3.1 days for patients taking rivaroxaban and 5.2±3.7 days for patients taking warfarin, confirmed by GLM-adjusted results (rivaroxaban 3.7 days, warfarin 5.3 days, P<0.001). Patients with provoked venous thromboembolism admissions showed longer LOSs (rivaroxaban 5.1±4.5 days, warfarin 6.5±5.6 days, P<0.001) than those with unprovoked venous thromboembolism (rivaroxaban 3.3±2.4 days, warfarin 4.8±2.8 days, P<0.001). Days from first dose to discharge were 2.4±1.7 for patients treated with rivaroxaban and 3.9±3.7 for patients treated with warfarin when initiated with parenteral anticoagulants (P<0.001), and 2.7±1.7 and 3.7±2.1, respectively, when initiated without parenteral anticoagulants (P<0.001). Patients initiated on rivaroxaban incurred significantly lower mean total hospitalization costs ($8688±$9927 versus $9823±$9319, P=0.004), confirmed by modeling (rivaroxaban $8387 [95% confidence interval, $8035-$8739]; warfarin $10 275 [95% confidence interval, $9842-$10 708]). Rivaroxaban was associated with significantly shorter hospital LOS and lower hospitalization costs compared with warfarin.

Margolis JM ，Deitelzweig S ，Kline J ，Tran O ，Smith DM ，Bookhart B ，Crivera C ，Schein J ... -  《Journal of the American Heart Association》