Effectiveness and safety of rivaroxaban versus warfarin in obese patients with acute venous thromboembolism: analysis of electronic health record data.

There is limited data evaluating clinical outcomes of rivaroxaban versus warfarin in obese patients with venous thromboembolism (VTE). Our objective was to evaluate the effectiveness and safety of rivaroxaban versus warfarin in obese VTE patients. We performed a cohort analysis using Optum® De-Identified Electronic Health Record data from 11/1/2012 to 9/30/2018. Patients with a body mass index (BMI) ≥ 30 kg/m2 admitted to the hospital, emergency department or observation unit for VTE, prescribed rivaroxaban or warfarin as their first oral anticoagulant (OAC) within 7-days and had ≥12-months of EHR activity prior were included. We excluded patients with OAC use at baseline or cancer. Patients were 1:1 matched (standard differences<0.10). Primary outcomes were recurrent VTE and major bleeding at 3-, 6- and 12-months using an intent-to-treat approach. Subanalyses of BMI 30.0-34.9, 35.0-39.9 and ≥ 40 kg/m2 were performed. Risk was compared using Cox regression and reported as hazard ratios (HRs) with 95% confidence intervals (CI). We identified 6755 rivaroxaban and 6755 warfarin users with BMI ≥ 30 kg/m2 and incident VTE. At 3-, 6- and 12-months, rivaroxaban was associated with a reduced hazard of recurrent VTE compared to warfarin (HR 0.61, 95%CI 0.51-0.72; HR 0.65, 95%CI 0.55-0.77; HR 0.63, 95%CI 0.54-0.74) with no difference in major bleeding (HR 0.99, 95%CI 0.68-1.44; HR 0.90, 95%CI 0.64-1.26; HR 1.00, 95%CI 0.73-1.36). No statistical difference was found across BMI categories for either recurrent VTE (p-interaction≥0.43) or major bleeding (p-interaction ≥ 0.58) at any time point. In obese VTE patients, prescription of rivaroxaban was associated with a significantly reduced risk of recurrent VTE versus warfarin, without impacting major bleeding. Our findings remained consistent across BMI classes.

Rivaroxaban versus apixaban in non-valvular atrial fibrillation patients with end-stage renal disease or receiving dialysis.

OBJECTIVES: We sought to evaluate the effectiveness and safety of rivaroxaban vs apixaban in non-valvular atrial fibrillation (NVAF) patients with end-stage renal disease (ESRD) and/or receiving dialysis in routine practice. METHODS: Using US MarketScan claims data from January 1, 2014, to December 31, 2017, we identified new-users of rivaroxaban or apixaban during 2015 with at least 12 months of insurance coverage prior to oral anticoagulant (OAC) initiation. Differences in baseline covariates between cohorts were adjusted using inverse probability-of-treatment weighting based on propensity scores. Patients were followed for stroke or systemic embolism (SSE) or major bleeding hospitalizations. Cox proportion hazards regression was used to compare rivaroxaban and apixaban. Analyses stratified by age, sex, CHA2DS2-VASc score, prior stroke, prior bleed, diabetes, and reduced OAC dose were performed. RESULTS: We identified 787 rivaroxaban and 1836 apixaban users. Median (25, 75% range) age = 70 (61, 79), CHA2DS2-VASc score = 3 (2, 4), and follow-up = 0.87 (0.38, 1.56) years. No differences in the risks of SSE (HR = 1.18, 95% CI = 0.53-2.63), ischemic stroke (HR = 1.12, 95%CI = 0.45-2.76), or major bleeding (HR = 1.00, 95% CI = 0.63-1.58) were observed. No significant interactions were observed upon subgroup analysis. CONCLUSION: In NVAF patients with ESRD and/or receiving dialysis, rivaroxaban and apixaban were associated with similar risks of SSE and major bleeding.

Rivaroxaban versus warfarin for treatment and prevention of recurrence of venous thromboembolism in African American patients: a retrospective cohort analysis.

BACKGROUND: African Americans are under-represented in trials evaluating oral anticoagulants for the treatment of acute venous thromboembolism (VTE). The aim of this study was to evaluate the effectiveness and safety of rivaroxaban versus warfarin for the treatment of VTE in African Americans. METHODS: We utilized Optum® De-Identified Electronic Health Record data from 11/1/2012-9/30/2018. We included African Americans experiencing an acute VTE during a hospital or emergency department visit, who received rivaroxaban or warfarin as their first oral anticoagulant within 7-days of the acute VTE event and had ≥1 provider visit in the prior 12-months. Differences in baseline characteristics between cohorts were adjusted using inverse probability-of-treatment weighting based on propensity scores (standard differences < 0.10 were achieved for all covariates). Our primary endpoint was the composite of recurrent VTE or major bleeding at 6-months. Three- and 12-month timepoints were also assessed. Secondary endpoints included recurrent VTE and major bleeding as individual endpoints. Cohort risk was compared using Cox regression and reported as hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: We identified 2097 rivaroxaban and 2842 warfarin users with incident VTE. At 6-months, no significant differences in the composite endpoint (HR = 0.96, 95%CI = 0.75-1.24), recurrent VTE (HR = 1.02, 95%CI = 0.76-1.36) or major bleeding alone (HR = 0.93, 95%CI = 0.59-1.47) were observed between cohorts. Analysis at 3- and 12-months provided consistent findings for these endpoints. CONCLUSIONS: In African Americans experiencing an acute VTE, no significant difference in the incidence of recurrent VTE or major bleeding was observed between patients receiving rivaroxaban or warfarin.

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

OBJECTIVES: To assess the association between rivaroxaban and warfarin and major bleeding risk in unprovoked venous thromboembolism (VTE) patients. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Effectiveness and safety of rivaroxaban and warfarin for prevention of major adverse cardiovascular or limb events in patients with non-valvular atrial fibrillation and type 2 diabetes.

AIMS: To assess the effectiveness and safety of rivaroxaban versus warfarin for the prevention of major adverse cardiovascular events (MACE) and major adverse limb events (MALE) in patients with type 2 diabetes (T2D) and non-valvular atrial fibrillation (NVAF). MATERIALS AND METHODS: Using MarketScan data from January 2012 to December 2017, we identified oral anticoagulant-naïve patients with NVAF and comorbid T2D and ≥12 months of insurance coverage prior to rivaroxaban or warfarin initiation. Differences in baseline covariates between cohorts were adjusted for using inverse probability of treatment weights based on propensity scores (absolute standardized differences <0.1 achieved for all covariates after adjustment). Patients were followed until a MACE, MALE or major bleeding event, oral anticoagulant discontinuation/switch, insurance disenrolment or end of data availability. Hazard ratios (HRs) and 95% confidence intervals (CIs) comparing the cohorts were calculated using Cox regression. RESULTS: We identified 10 700 rivaroxaban users (24.1% received a reduced dose) and 13 946 warfarin users. The median (25%, 75% range) age was 70 (62, 79) years, CHA2DS2-VASc score was 4 (3, 5) and duration of available follow-up was 1.4 (0.6, 2.7) years. Eleven percent of patients had peripheral artery disease, 5.1% had coronary artery disease, and 5.1% had a prior MALE, at baseline. Rivaroxaban was associated with a 25% (95% CI 4-41) reduced risk of MACE and a 63% (95% CI 35-79) reduced risk of MALE compared to warfarin. Major bleeding risk did not significantly differ between cohorts (HR 0.95). CONCLUSIONS: Among patients with NVAF and T2D treated in routine practice, rivaroxaban was associated with lower risks of both MACE and MALE versus warfarin, with no significant difference in major bleeding.

Methods for Measuring Multiple Medication Adherence: A Systematic Review-Report of the ISPOR Medication Adherence and Persistence Special Interest Group.

BACKGROUND: A broad literature base exists for measuring medication adherence to monotherapeutic regimens, but publications are less extensive for measuring adherence to multiple medications. OBJECTIVES: To identify and characterize the multiple medication adherence (MMA) methods used in the literature. METHODS: A literature search was conducted using PubMed, PsycINFO, the International Pharmaceutical Abstracts, the Cumulative Index to Nursing and Allied Health Literature and the Cochrane Library databases on methods used to measure MMA published between January 1973 and May 2015. A two-step screening process was used; all abstracts were screened by pairs of researchers independently, followed by a full-text review identifying the method for calculating MMA. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed to conduct this systematic review. For studies that met the eligibility criteria, general study and adherence-specific characteristics and the number and type of MMA measurement methods were summarized. RESULTS: The 147 studies that were included originated from 32 countries, in 13 disease states. Of these studies, 26 used proportion of days covered, 23 used medication possession ratio, and 72 used self-reported questionnaires (e.g., the Morisky Scale) to assess MMA. About 50% of the studies included more than one method for measuring MMA, and different variations of medication possession ratio and proportion of days covered were used for measuring MMA. CONCLUSIONS: There appears to be no standardized method to measure MMA. With an increasing prevalence of polypharmacy, more efforts should be directed toward constructing robust measures suitable to evaluate adherence to complex regimens. Future research to understand the validity and reliability of MMA measures and their effects on objective clinical outcomes is also needed.

Safety and effectiveness of oral factor Xa inhibitors versus warfarin in nonvalvular atrial fibrillation patients at high-risk for falls.

Prescribers' concern regarding falls resulting in intracranial hemorrhage is often cited as a justification for under-utilization of oral anticoagulation. We evaluated the safety and effectiveness of oral factor Xa inhibitors versus warfarin in nonvalvular atrial fibrillation patients at high-risk for falls. Using MarketScan claims from 11/2012-3/2017, we identified adult, oral anticoagulation-naïve, new-initiators of oral factor Xa inhibitors or warfarin with nonvalvular atrial fibrillation, ≥ 12 months of insurance coverage prior to starting oral anticoagulation and a predicted 2-year risk of falls ≥ 15%. Differences in baseline covariates between cohorts were balanced using inverse probability-of-treatment weights based on propensity scores. Hazard ratios (HRs) and 95% confidence intervals (CIs) for intracranial hemorrhage and stroke or systemic embolism were estimated. Among 25,144 nonvalvular atrial fibrillation patients at high-risk for falls (observed fall rate = 11.8%/person-year), oral factor Xa inhibitor use was associated with a 43% (95% CI = 5-65%) reduced hazard of intracranial hemorrhage compared to warfarin. Oral factor Xa inhibitors did not significantly reduce the hazard of stroke or systemic embolism versus warfarin (HR = 0.86, 95% CI = 0.66-1.11). Findings for the intracranial hemorrhage and stroke or systemic embolism endpoints were similar when apixaban and rivaroxaban were evaluated separately versus warfarin (p-interaction ≥ 0.64 for all). Oral factor Xa inhibitors reduced patients' risk of intracranial hemorrhage and were at least as effective in preventing stroke or systemic embolism as warfarin in nonvalvular atrial fibrillation patients at high-risk for falls.

Effectiveness and Safety of Rivaroxaban in Patients With Cancer-Associated Venous Thrombosis.

Background: Although not designated as guideline-recommended first-line anticoagulation therapy, patients are receiving rivaroxaban for the treatment and secondary prevention of cancer-associated venous thrombosis (CAT). We sought to estimate the cumulative incidence of recurrent venous thromboembolism (VTE), major bleeding, and mortality/hospice care in patients with CAT treated with outpatient rivaroxaban in routine practice. Methods: Using US MarketScan claims data from January 2012 through June 2015, we identified adults with active cancer (using SEER program coding) who had ≥1 primary hospitalization or emergency department discharge diagnosis code for VTE (index event) and received rivaroxaban as their first outpatient anticoagulant within 30 days of the index VTE. Patients were required to have ≥180 days of continuous medical/prescription benefits prior to the index VTE. Patients with a previous claim for VTE, atrial fibrillation, or valvular disease or receiving anticoagulation during the baseline period were excluded. We estimated the cumulative incidence with 95% CIs of recurrent VTE, major bleeding, and mortality or need for hospice care at 180 days, assuming competing risks. Results: A total of 949 patients with active cancer were initiated on rivaroxaban following their index VTE. Time from active cancer diagnosis to index CAT was ≤90 days for 27% of patients, 91 to 180 days for 19%, and >180 days for 54%. The mean [SD] age of patients was 62.5 [12.8] years, 43.6% had pulmonary embolism, and metastatic disease was present in 42.6%. During follow-up, there were 37 cases of recurrent VTE, 22 cases of major bleeding (17 gastrointestinal, 3 intracranial, 1 genitourinary, and 1 other bleed), and 105 deaths/hospice claims. The cumulative incidence estimate was 4.0% (95% CI, 2.8%-5.4%) for recurrent VTE, 2.7% (95% CI, 1.7%-4.0%) for major bleeding, and 11.3% (95% CI, 9.2%-13.6%) for mortality/hospice care. Conclusions: Event rates observed in this rivaroxaban-treated cohort were overall consistent with previous studies of patients with rivaroxaban- and warfarin-managed CAT.

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

A paucity of real-world data evaluating rivaroxaban in provoked venous thromboembolism (VTE) exists. We assessed the effectiveness and safety of rivaroxaban versus warfarin in provoked VTE patients treated in routine practice. Using MarketScan claims data from 1/2012 to 12/2016, we identified adults who had ≥ 1 primary hospitalization/emergency department discharge diagnosis code for VTE (index event) and a provoking factor, received rivaroxaban or warfarin as their first outpatient oral anticoagulant within 30-days of the index event and had ≥ 12-month of insurance coverage prior the index VTE. Provoking factors included cancer, hospital admission for ≥ 3-consecutive days over the prior 3-months, major surgery, trauma or fracture within 90-days or pregnancy within 42-weeks of the index VTE. Differences in baseline covariates between cohorts were adjusted using inverse probability-of-treatment weights based on propensity-scores (residual standardized differences < 0.1 achieved for all covariates after adjustment). The incidence of the composite endpoint of recurrent VTE or major bleeding at 3- and 6-months was compared using Cox regression and reported as hazard ratios (HRs) and 95% confidence intervals (CIs). We included 4454 rivaroxaban and 13,164 warfarin users with provoked VTE. At 3- and 6-months, rivaroxaban was associated with a reduced hazard of the composite endpoint (HR 0.72, 95% CI 0.61-0.84 and HR 0.69, 95% CI 0.60-0.80) and recurrent VTE (HR 0.70, 95% CI 0.59-0.84 and HR 0.71, 95% CI 0.60-0.84) versus warfarin. Major bleeding was non-significantly reduced at 3-months (HR 0.77, 95% CI 0.57-1.06) and significantly reduced at 6-months (HR 0.68, 95% CI 0.53-0.88) with rivaroxaban. Rivaroxaban reduces recurrent VTE and major bleeding risk versus warfarin in provoked VTE patients treated in routine practice.

Effectiveness and Safety of Apixaban, Dabigatran, and Rivaroxaban Versus Warfarin in Patients With Nonvalvular Atrial Fibrillation and Previous Stroke or Transient Ischemic Attack.

BACKGROUND AND PURPOSE: Limited real-world data exist comparing each non-vitamin K antagonist oral anticoagulant (NOAC) to warfarin in patients with nonvalvular atrial fibrillation who have had a previous ischemic stroke or transient ischemic attack. METHODS: Using MarketScan claims from January 2012 to June 2015, we identified adults newly initiated on oral anticoagulation, with ≥2 diagnosis codes for nonvalvular atrial fibrillation, a history of previous ischemic stroke/transient ischemic attack, and ≥180 days of continuous medical and prescription benefits before anticoagulation initiation. Three analyses were performed comparing 1:1 propensity score-matched cohorts of apixaban versus warfarin (n=2514), dabigatran versus warfarin (n=1962), and rivaroxaban versus warfarin (n=5208). Patients were followed until occurrence of a combined end point of ischemic stroke and intracranial hemorrhage (ICH) or major bleed, switch/discontinuation of index oral anticoagulation, insurance disenrollment, or end of follow-up. Mean follow-up was 0.5 to 0.6 years for all matched cohorts. RESULTS: Using Cox regression, neither apixaban nor dabigatran reduced the combined primary end point of ischemic stroke or ICH (hazard ratio [HR], 0.70; 95% confidence interval [CI], 0.33-1.48 and HR, 0.53; 95% CI, 0.26-1.07) and had nonsignificant effect on hazards of major bleeding (HR, 0.79; 95% CI, 0.38-1.64 and HR, 0.58; 95% CI, 0.26-1.27) versus warfarin. Rivaroxaban reduced the combined end point of ischemic stroke or ICH (HR, 0.45; 95% CI, 0.29-0.72) without an effect on major bleeding (HR, 1.07; 95% CI, 0.71-1.61). ICH occurred at rates of 0.16 to 0.61 events per 100 person-years in the 3 NOAC analyses, with no significant difference for any NOAC versus warfarin. CONCLUSIONS: Results from our study of the 3 NOACs versus warfarin in nonvalvular atrial fibrillation patients with a previous history of stroke/transient ischemic attack are relatively consistent with their respective phase III trials and previous stroke/transient ischemic attack subgroup analyses. All NOACs seemed no worse than warfarin in respect to ischemic stroke, ICH, or major bleeding risk.

Observation management of pulmonary embolism and agreement with claims-based and clinical risk stratification criteria in United States patients: a retrospective analysis.

BACKGROUND: Guidelines suggest observation stays are appropriate for pulmonary embolism (PE) patients at low-risk for early mortality. We sought to assess agreement between United States (US) observation management of PE and claims-based and clinical risk stratification criteria. METHODS: Using US Premier data from 11/2012 to 3/2015, we identified adult observation stay patients with a primary diagnosis of PE, ≥1 PE diagnostic test claim and evidence of PE treatment. The proportion of patients at high-risk was assessed using the In-hospital Mortality for PulmonAry embolism using Claims daTa (IMPACT) equation and high-risk characteristics (age > 80 years, heart failure, chronic lung disease, renal or liver disease, high-risk for bleeding, cancer or need for thrombolysis/embolectomy). RESULTS: We identified 1633 PE patients managed through an observation stay. Despite their observation status, IMPACT classified 46.4% as high-risk for early mortality and 33.3% had ≥1 high-risk characteristic. Co-morbid heart failure, renal or liver disease, high-risk for major bleeding, cancer and hemodynamic instability were low (each <4.5%), but 7.8% were >80 years-of-age and 19.4% had chronic lung disease. CONCLUSION: Many PE patients selected for management in observation stay units appeared to have clinical characteristics suggestive of higher-risk for mortality based upon published claims-based and clinical risk stratification criteria.

Outcomes associated with observation stays versus inpatient admissions for pulmonary embolism.

Changes in reimbursement policies have led to an increased use of observation stays in the United States (US). We sought to compare outcomes among pulmonary embolism (PE) patients managed through observation stays or inpatient admissions.The Premier Perspective Comparative Hospital Database was used to identify patients with a primary International Classification of Diseases, ninth-edition diagnosis of PE (415.1×) from 11/2012-3/2015. Patients were required to have claims for ≥1 diagnostic tests for PE on days 0-2 and evidence of PE treatment. Patients managed through observation stays were 1:1 propensity score matched to those undergoing inpatient admissions. We compared length-of-stay (LOS), hospital costs (2015US$) and rates of hospital-acquired conditions and readmission between the cohorts. A total of 1105 PE observation stays were matched to 1105 inpatient admissions. The baseline characteristics of the cohorts were well-balanced (no standardized differences >10 %). Mean ± standard deviation LOS and hospital costs were 3.6 ± 2.6 days and $5423 ± $5770, respectively. LOS was shorter for observation stays 2.3 ± 1.3 days) vs. inpatient admissions (4.9 ± 3.0 days, p < 0.001). This corresponded to a mean $4390 lower treatment costs for observation stays (p < 0.001). Hospital-acquired conditions were less common among observation stay patients vs. inpatients (p < 0.001); driven predominantly by reductions in bacterial pneumonia and Clostridium difficile infection. Readmission for venous thromboembolism or major bleeding in the same or subsequent 2-months did not differ between the cohorts (p ≥ 0.16 for both).Compared with inpatient admissions, observation stays were associated with reduced LOS, costs and hospital-acquired conditions, without increased risk of readmission.

Adherence and persistence to rivaroxaban in non-valvular atrial fibrillation patients receiving 30- or 90-day supply prescription fills.

BACKGROUND: It is unclear whether 90-day supply fills with rivaroxaban result in better adherence and persistence compared to 30-day supply fills. We assessed patients' adherence and persistence to rivaroxaban at 12- and 24-months in nonvalvular atrial fibrillation (NVAF) patients whose rivaroxaban prescriptions were filled every 30- vs. 90-days. METHODS: Using the IBM MarketScan Commercial and Medicare Supplemental data sets, we identified adult NVAF patients with ≥12-months of continuous insurance coverage who filled a prescription in May 2018 and their immediate subsequent prescription for rivaroxaban for the same days' supply. We propensity score-matched 30- and 90-day rivaroxaban interval fill patients and compared the percentage with a proportion of days covered (PDC) ≥80%, mean PDC, and percentage persistent to rivaroxaban therapy over 12- and 24-months of follow-up. RESULTS: Following propensity score matching, 2237 patients were included in the rivaroxaban 30- and 90-day supply fill cohorts. The proportion of patients with a PDC ≥80% was greater in the 90-day vs. 30-day cohort at both 12-months (odds ratio [OR] = 1.75, 95% confidence interval [CI] = 1.54-1.97) and 24-months (OR = 1.78, 95%CI = 1.58-2.00), as were mean PDC values (absolute difference in mean PDC = 9.4%, 95%CI = 8.2-10.7% at 12-months and 11.2%, 95%CI = 9.5-12.9% higher at 24-months, respectively). Persistence to rivaroxaban was not found to significantly differ between the 30- and 90-day supply cohorts at 12- or 24-months (assuming a 30-day permissible gap); however, greater persistence was observed with 90-day fills at both time points when a 14-day gap was utilized (HR = 1.22, 95%CI = 1.10-1.36 at 12-months and HR = 1.12, 95%CI = 1.02-1.22 at 24-months). CONCLUSIONS: Dispensing 90-day supply fills with rivaroxaban appears to increase the proportion of patients achieving acceptable (PDC ≥80%) adherence as well as mean adherence compared to 30-day supply fills. Ninety-day rivaroxaban fills may also result in improved persistence vs. 30-day fills.

Identification and Outcomes of Hospitalized Medically Ill Patients Who Are Candidates for Extended Duration Thromboprophylaxis.

Background Extended duration thromboprophylaxis (ET) for approximately 30 days can effectively and safely reduce venous thromboembolism (VTE) risk in appropriately selected medically ill patients. We sought to estimate the proportion of hospitalized medically ill patients potentially qualifying for ET and assess their post-discharge clinical and economic outcomes using a large claims database. Methods Using MarketScan claims from January 2012 to September 2018, we identified medically ill patients hospitalized with a primary diagnosis of heart failure, respiratory insufficiency, ischemic stroke, infection, or inflammatory disease and ≥1-additional risk factor for VTE. Patients < 40 years old, a length-of-stay < 3 or >30 days, receiving oral anticoagulation prior to index hospitalization or having an indication for full-dose anticoagulation were excluded, as were patients deemed high-risk for bleeding due to active, in-hospital treated cancer, gastroduodenal ulcer or bleeding within the prior 3 months, bronchiectasis, pulmonary cavitation or hemorrhage, or dual antiplatelet therapy use. Results We identified 2,782,988 patients ≥40 years of age and admitted for a high-risk medical illness. Of these, 724,531 patients (26.0%) were identified as ET candidates. Patients' VTE risk appeared highest in the first 30 days post-discharge (1,532/724,531, 0.2%). Adjusted post-index hospitalization costs (2018 US$) for patients with a VTE within 30 days were higher than those without VTE (Δ = $32,623 at 30 days, Δ = $43,325 at 90 days, Δ = $53,668 at 365 days; p < 0.001 for all). Conclusion Post-discharge VTE in high-risk patients with medical illness is associated with substantially increased costs.

Rivaroxaban Versus Warfarin in African American Patients with Nonvalvular Atrial Fibrillation.

INTRODUCTION: Black patients are under-represented in randomized trials evaluating oral anticoagulants in non-valvular atrial fibrillation (NVAF). We sought to evaluate the effectiveness and safety of rivaroxaban versus warfarin in African Americans with NVAF. METHODS: We performed an analysis using Optum® De-Identified Electronic Health Record (EHR) data from 1/1/2012-9/30/2018. We included adult African American patients with a diagnosis of NVAF who were anticoagulant-naïve during the 12-months prior to initiation of rivaroxaban or warfarin. Patients receiving rivaroxaban were 1:1 propensity score matched to warfarin patients. Our primary effectiveness and safety outcomes were the 2-year incidence rates (%/year) of stroke or systemic embolism (SSE) and major bleeding using an intention-to-treat approach. Cohorts were compared using doubly-robust Cox regression and reported as hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: We matched 4102 rivaroxaban and 4102 warfarin users with a median (interquartile range) available follow-up of 2.0 (0.9, 2.0) years. Median CHA2DS2-VASc and HASBLED scores were 3 (2, 4) and 2 (1, 3). Rivaroxaban use was associated with a lower risk of SSE (1.99 versus 2.48, HR = 0.77, 95%CI = 0.60-0.99), ischemic stroke (1.84 versus 2.37, HR = 0.76, 95%CI = 0.59-0.98) and major bleeding (4.22 versus 4.98, HR = 0.84, 95%CI = 0.70-0.99). No differences in intracranial hemorrhage or gastrointestinal bleeding were observed. Neither sensitivity analyses utilizing an on-treatment methodology nor inverse probability-of-treatment weighting showed significant differences in SSE or major bleeding between rivaroxaban and warfarin users. CONCLUSIONS: Rivaroxaban appeared at least as effective and safe as warfarin when used to manage African American patients with NVAF in routine practice.

Effectiveness and safety of rivaroxaban compared with low-molecular-weight heparin in cancer-associated thromboembolism.

Guidelines provide differing recommendations regarding direct-acting oral anticoagulants vs low-molecular-weight heparin (LMWH) for treatment of cancer-associated thrombosis (CAT). This study was undertaken to evaluate the effectiveness and safety of rivaroxaban vs LMWH for treatment of CAT. Using US Surveillance, Epidemiology and End Results-Medicare-linked data from 2013 through 2016, we evaluated adults with active breast, lung, ovarian, or pancreatic cancer, who were admitted to the hospital or treated in the emergency department for CAT and were prescribed rivaroxaban or LMWH for outpatient anticoagulation. Patients with luminal gastrointestinal or genitourinary cancers were excluded. Rivaroxaban and LMWH users were 1:1 propensity score matched. Outcomes included the composite of recurrent thrombosis or major bleeding, each outcome separately, and mortality at 6 months, using an intent-to-treat approach. On-treatment analysis after 12 months was also performed. Proportional hazards models for the subdistribution of competing risk were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). We included 529 rivaroxaban- and 529 LMWH-treated patients with CAT. Rivaroxaban was not associated with differences in risk of the composite outcome (HR, 0.71; 95% CI, 0.41-1.22), major bleeding (HR, 1.01; 95% CI, 0.50-2.01), or mortality (HR, 0.87; 95% CI, 0.70-1.07) vs LMWH, but it reduced recurrent thrombosis (HR, 0.37; 95% CI, 0.15-0.95). On-treatment analysis at 12 months showed similar results. Rivaroxaban may be a reasonable alternative to LMWH for patients with CAT without gastrointestinal or genitourinary cancer.

Rivaroxaban Versus Warfarin for Management of Obese African Americans With Non-Valvular Atrial Fibrillation or Venous Thromboembolism: A Retrospective Cohort Analysis.

African Americans (AAs) and obese individuals have increased thrombotic risk. This study evaluated the effectiveness and safety of rivaroxaban versus warfarin in obese, AAs with nonvalvular atrial fibrillation (NVAF) or venous thromboembolism (VTE). Optum® De-Identified Electronic Health Record (EHR) data was used to perform separate propensity-score matched analyses of adult, oral anticoagulant (OAC)-naïve AAs with NVAF or acute VTE, respectively; who had a body mass index≥30kg/m2 and ≥12-months EHR activity with ≥1-encounter before OAC initiation. Cox regression was performed and reported as hazard ratios (HRs) with 95% confidence intervals (CIs). For the NVAF analysis, 1,969 rivaroxaban- and 1,969 warfarin-users were matched. Rivaroxaban was not associated with a difference in stroke/systemic embolism versus warfarin (HR = 0.88, 95%CI = 0.60-1.28), but less major bleeding (HR = 0.68, 95%CI = 0.50-0.94) was observed. Among 683 rivaroxaban-users with VTE, 1:1 matched to warfarin-users, rivaroxaban did not alter recurrent VTE (HR = 1.36, 95%CI = 0.79-2.34) or major bleeding (HR = 0.80, 95%CI = 0.37-1.71) risk versus warfarin at 6-months (similar findings observed at 3- and 12-months). Rivaroxaban appeared to be associated with similar thrombotic, and similar or lower major bleeding risk versus warfarin in these obese, AA cohorts.

Effectiveness and safety of rivaroxaban versus warfarin in obese nonvalvular atrial fibrillation patients: analysis of electronic health record data.

Background: Although rivaroxaban has demonstrated consistent drug levels in normal weight and obese patients, sufficient confirmation of equal clinical effectiveness and safety is currently lacking.Purpose: To evaluate the effectiveness and safety of rivaroxaban versus warfarin for prevention of stroke and systemic embolism (SSE) in obese nonvalvular atrial fibrillation (NVAF) patients.Methods: Using Optum de-identified Electronic Health Record (EHR) data from November 2011 to September 2018,we evaluated NVAF patients with a body mass index (BMI)≥30 kg/m2 newly initiated on rivaroxaban or warfarin (index date), with ≥12-months of EHR activity and ≥1 encounter before the index date. We excluded patients with valvular disease or evidence of oral anticoagulant (OAC) use at baseline. Patients who were prescribed rivaroxaban were 1:1 propensity-score matched to patients who were prescribed warfarin (standard differences <0.10 achieved for all covariates). Outcomes included SSE and major bleeding using an intent-to-treat approach. Subanalyses stratified by BMI (30.0-34.9, 35.0-39.9 and ≥40 kg/m2) were performed. Cox regression was performed and reported as hazard ratios (HRs) and 95% confidence intervals (CIs).Results: We included 35,613 rivaroxaban and 35,613 warfarin users with NVAF. Patients were followed for a median of 2.6 years (25%-75% range = 1.2-4.1). Rivaroxaban was associated with a reduced risk of SSE (HR = 0.83, 95%CI = 0.73-0.94) and major bleeding (HR = 0.82, 95%CI = 0.75-0.89) compared to warfarin. Subanalysis did not show a statistically significant interaction across BMI categories for SSE (p-interaction = .58) or major bleeding (p-interaction = .44) outcomes.Conclusions: Among obese NVAF patients, prescription of rivaroxaban was associated with a reduced risk of SSE and major bleeding compared to warfarin, which remained consistent across BMI classes.

Effectiveness and safety of rivaroxaban vs. warfarin in patients with non-valvular atrial fibrillation and coronary or peripheral artery disease.

AIMS: There are scarce data evaluating the effectiveness and safety of rivaroxaban vs. warfarin in non-valvular atrial fibrillation (NVAF) patients with concomitant coronary artery disease (CAD) and/or peripheral artery disease (PAD) treated in routine practice. METHODS AND RESULTS: Using MarketScan data from January 2012 to December 2017, we identified oral anticoagulant (OAC)-naïve NVAF patients receiving rivaroxaban (15-20 mg once daily) or warfarin, with comorbid CAD and/or PAD and ≥12 months of insurance coverage before OAC initiation. Differences in baseline covariates between cohorts were adjusted using inverse probability-of-treatment weights based on propensity scores (standardized differences <0.1 achieved for all covariates after adjustment). Endpoints included a composite of major thrombotic vascular events (MTVEs) (including ischaemic stroke, myocardial infarction, or need for lower limb revascularization/major amputation) and major bleeding. Patients were followed until an event-of-interest, discontinuation/switch of index OAC, insurance disenrolment, or end-of-data availability. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox regression. We identified 3257 rivaroxaban (30.4% received a 15 mg dose) and 5046 warfarin users with NVAF and comorbid CAD and/or PAD. Rivaroxaban was associated with a 32% (95% CI = 8-50%) reduction in the composite of MTVE. No significant difference in major bleeding was observed (HR = 1.13, 95% CI = 0.84-1.52). No statistical interactions were noted in subgroup analyses performed on the MTVE (P-interaction ≥ 0.35 for all) or major bleeding endpoints (P-interaction ≥ 0.09 for all). CONCLUSION: Among patients with NVAF and comorbid CAD and/or PAD, rivaroxaban use was associated with a reduced risk of MTVEs vs. warfarin, without significantly increasing major bleeding risk.