CMS hospital readmission reduction program and anticoagulants received following a total hip and knee arthroplasty discharge.

OBJECTIVES: To assess association between 30 day readmission rate and treatment received after total hip and knee arthroplasty (THA/TKA) discharge (rivaroxaban vs. warfarin or non-anticoagulant). To subsequently model impact of increasing rivaroxaban use on the Hospital Readmission Reduction Program (HRRP) penalty, which was imposed on hospitals with excess 30 day readmissions after hospitalizations for selected conditions, including THA/TKA. METHODS: The US Truven Health MarketScan Medicare Supplemental database from 1 July 2010 to 30 April 2015 was used. A retrospective claims analysis was conducted to assess the risk of all-cause 30 day readmission among patients receiving either rivaroxaban or warfarin, or no anticoagulation following THA/TKA discharge. Simulations were performed to estimate the impact of post-discharge treatment on the HRRP penalty. RESULTS: The risk-adjusted all-cause 30 day readmission rates were 1.21% (95% confidence interval [95% CI]: 0.94%-1.49%), 1.41% (95% CI: 1.19%-1.58%) and 1.95% (95% CI: 1.81%-2.11%) for rivaroxaban, warfarin and non-anticoagulant cohorts, respectively. Using these rates, simulations illustrated that when switching patients from warfarin or non-anticoagulant to rivaroxaban, annual penalty per hospital would be reduced up to 67% or 88%, respectively. CONCLUSIONS: Rivaroxaban treatment post-THA/TKA discharge reduced the risk of 30 day readmission compared to non-anticoagulants. Simulations illustrated that increasing rivaroxaban use could decrease the HRRP penalty.

Effectiveness and safety of anticoagulants for the treatment of venous thromboembolism in patients with cancer.

Anticoagulation is used to treat venous thromboembolism (VTE) in cancer patients, but may be associated with an increased risk of bleeding. VTE recurrence and major bleeding were assessed in cancer patients treated for VTE with the most currently prescribed anticoagulants in clinical practice. Newly diagnosed cancer patients (first VTE 1/1/2013-05/31/2015) who initiated rivaroxaban, low-molecular-weight heparin (LMWH), or warfarin were identified from Humana claims data and observed until end of eligibility or end of data availability. VTE recurrence was a hospitalization with a primary diagnosis of VTE ≥7 days after first VTE. Major bleeding events on treatment were identified using validated criteria. Cohorts were compared using Kaplan-Meier rates at 6 and 12 months and Cox proportional hazards models. Cohorts were adjusted for their differences at baseline. A total of 2428 patients (rivaroxaban: 707; LMWH: 660; warfarin: 1061) met inclusion criteria. Patient characteristics were well balanced after weighting. There was a trend for lower VTE recurrence rates in rivaroxaban users compared to LMWH users at 6 months (13.2% vs. 17.1%; P = .060) and significantly lower at 12 months (16.5% vs. 22.2%; P = .030) [HR: 0.72, 95% CI: (0.52-0.95); P = .024]. VTE recurrence rates were also lower for rivaroxaban than warfarin users at 6 months (13.2% vs. 17.5%; P = .014) and 12 months (15.7% vs. 19.9%; P = .017) [HR: 0.74, 95% CI: (0.56-0.96); P = .028]. Major bleeding rates were similar across cohorts. This real-world analysis suggests cancer patients with VTE treated with rivaroxaban had significantly lower risk of recurrent VTE and similar risk of bleeding compared to those treated with LMWH or warfarin.

Association between rivaroxaban use and length of hospital stay, treatment costs and early outcomes in patients with pulmonary embolism: a systematic review of real-world studies.

BACKGROUND: In the EINSTEIN-Pulmonary Embolism (PE) trial, subjects randomized to rivaroxaban versus enoxaparin bridging to vitamin K antagonist (VKA) therapy experienced a reduced index hospital length of stay (LOS). We sought to conduct a systematic review of real-world studies comparing LOS, costs and early outcomes among patients treated with rivaroxaban or parenterally bridged VKA in routine practice. METHODS: We searched Medline and Scopus from 1 January 2011 to 30 November 2016 to identify observational studies comparing acute PE patients anticoagulated with rivaroxaban or parenterally bridged VKA and reporting data on index hospital LOS, costs and/or early post-PE outcomes. Studies not using appropriate methods for minimizing confounding bias or not published in English were excluded. RESULTS: Five studies met inclusion criteria. Rivaroxaban use was associated with decreased index hospital LOS (range: 1.36-1.70 days) and treatment costs (range: $1818-$2688) during an index stay compared to parenterally bridged warfarin. No differences in early readmission for recurrent thrombosis were noted between anticoagulation strategies. Readmission for major bleeding was rare in both cohorts. Similar reductions in LOS (range: 0.23-4.3 days) and costs (range: $251-$7094) were observed with rivaroxaban in studies restricted to patients deemed low risk for early complications by clinical gestalt or by a clinical- or claims-based risk stratification tool. CONCLUSIONS: Regardless of patient predicted risk of post-PE complications, real-world studies suggest that rivaroxaban is associated with a reduced hospital LOS and costs versus parenterally bridged warfarin, without increasing readmission.

Risk for Venous Thromboembolism Recurrence Among Rivaroxaban-treated Patients Who Continued Versus Discontinued Therapy: Analyses Among Patients with VTE.

PURPOSE: The EINSTEIN-Extension trial showed that an extended rivaroxaban treatment significantly reduced the risk for venous thromboembolic (VTE) recurrence. The present study assessed the risk for VTE recurrence and major bleeding associated with extended rivaroxaban treatment in a clinical practice setting among patients with VTE. METHODS: A retrospective study was conducted using claims data from February 2011 to April 2015. It included adult patients who initiated rivaroxaban therapy within 7 days after their first VTE and who continuously used rivaroxaban for at least 3 months (index date: end of initial 3-month treatment). Categorized into discontinued and continued cohorts, patients were followed up from the index date until the end of continuous treatment (continued cohort) or end of data or reinitiation of oral anticoagulant therapy (discontinued cohort). Using inverse probability of treatment weights controlling for confounders, adjusted Kaplan-Meier rates of recurrent VTE and major bleeding events were compared. FINDINGS: The analysis showed that, compared with the discontinued cohort (n = 1,536), the continued cohort (n = 5,933) had a significantly lower VTE recurrence rate after an additional 3 months (0.70% vs 1.70%), 6 months (1.41% vs 2.34%), 9 months (1.82% vs 3.01%), and 12 months (1.97% vs 3.01%) of treatment (all, p < 0.05). The difference in the cumulative event rates for major bleeding was not statistically significant. Similar results were obtained in an analysis among patients with VTE receiving rivaroxaban for ≥6 months. IMPLICATIONS: Our results suggest that, in clinical practice settings, patients with VTE who continued rivaroxaban therapy after the initial 3- or 6-month treatment period had a significantly lower risk for VTE recurrence without a statistically significant increased risk for major bleeding.

Overall Effectiveness of Rivaroxaban in Patients with Pulmonary Embolism.

PURPOSE: Due to limited evidence on the impact of rivaroxaban in clinical practice, we compared the effectiveness of rivaroxaban versus standard of care (SOC) among patients in the Veterans Health Administration. METHODS: Adult patients with continuous enrollment in a health plan with medical and pharmacy benefits for ≥12 months before and ≥3 months after an inpatient diagnosis of pulmonary embolism (PE) between October 1, 2011, and June 30, 2015, and a prescription claim for an anticoagulant during the index hospitalization, were included. SOC drugs were low-molecular-weight heparin, unfractionated heparin, and warfarin. Propensity score matching was used in comparing PE-related outcomes (recurrent venous thromboembolism, major bleeding, and death), hospital-acquired complications (HACs), health care resource utilization, and costs among patients receiving SOC versus rivaroxaban. We defined net clinical benefit as 1 minus the combined rate of PE-related outcomes and HACs. FINDINGS: Among 6746 patients with PE, 208 received rivaroxaban, 4641 received SOC and 1897 received other anticoagulants. Most (95%) were male; 22% were black. After 1:3 propensity score matching, there were 203 rivaroxaban and 609 SOC patients. During the 90-day follow-up, rivaroxaban users had similar rates of PE-related outcomes, but fewer had experienced at least 1 HAC (10.3% vs 15.9%; P = 0.0506), resulting in better net clinical benefit (82.8% vs 71.1%; P = 0.001). Rivaroxaban users had fewer outpatient visits per patient (17.0 vs 19.9; P = 0.0005), a similar rehospitalization rate (0.2 vs 0.3; P = 0.084), lesser inpatient costs (US $3501 vs $6189; P < 0.0001), lesser inpatient costs and lesser total costs ($10,545 vs $14,192; P = 0.0002). When the sample was limited to patients with low-risk PE, we found similar patterns. IMPLICATIONS: Patients with PE prescribed rivaroxaban had similar PE-related outcomes, but fewer HACs and lesser total costs, than did patients on SOC.

Importance of balancing follow-up time and impact of oral-anticoagulant users' selection when evaluating medication adherence in atrial fibrillation patients treated with rivaroxaban and apixaban.

OBJECTIVE: Studies comparing medications adherence have become common yet they often do not account for differences in relative follow-up. Patient selection criteria may impact validity and comparability of these studies as well. METHODS: Adults with non-valvular atrial fibrillation, ≥1 rivaroxaban or apixaban dispensing (index date), and ≥1 year of pre-index eligibility were selected from IMS Health Real World Data Adjudicated Claims (IMS RWD Adjudicated Claims) and Truven Health MarketScan Research (Truven MarketScan) databases. Adherence was evaluated using proportion of days covered (PDC) ≥ 0.8 for treatment cohorts: (1) unmatched, with different follow-up, (2) propensity-score matched with similar follow-up, (3) matched, with similar follow-up and ≥2 rivaroxaban or apixaban dispensings, and (4) matched, with similar follow-up and chronic medication users only. Robustness was verified with PDC ≥0.9. RESULTS: In the IMS RWD Adjudicated Claims database, rivaroxaban users had a longer mean follow-up than apixaban users (408 versus 254 days, respectively; p < .01). While crude comparisons demonstrated lower adherence rates for rivaroxaban than apixaban (-12.4 percentage points [pp]; p < .05), these difference attenuated after matching and (1) balancing follow-up (-2.2 pp; p < .05), (2) excluding single-time medication users (0.2 pp; p > .05), and reversed after (3) excluding non-chronic medication users (5.0 pp; p < .05). Results obtained were consistent when these analyses were repeated within the Truven MarketScan databases and when using a PDC ≥0.9. CONCLUSION: Medication adherence comparisons need to account for differences in follow-up. Selection of chronic medication users may impact comparative adherence advantage between medications.

Shortened hospital length of stay and lower costs associated with rivaroxaban in patients with pulmonary embolism managed as observation status.

BACKGROUND: Unlike rivaroxaban, treatment of patients with pulmonary embolism (PE) with warfarin requires parenteral bridging and coagulation monitoring that may prolong length-of-stay (LOS) and increase hospital costs. AIMS: The aim of this study was to compare LOS, hospital costs and readmissions in PE patients managed through observation stays treated with rivaroxaban or parenterally bridged warfarin. METHODS: Premier Hospital claims data from November 2012 to March 2015 were used to identify patients with a primary diagnosis code for PE managed through an observation stay and with ≥1 claim for a PE-related diagnostic test on day 0-2. Rivaroxaban users, allowing ≤2 days of prior parenteral therapy, were 1:1 propensity-score matched to patients receiving parenterally bridged warfarin. LOS, the proportion of encounters lasting >2 midnights, total hospital costs of the index visit and risk of readmission for venous thromboembolism (VTE) or major bleeding during the same month or 2 months subsequent to the index event were compared between matched cohorts using multivariable regression. RESULTS: A total of 312 rivaroxaban users were matched to 312 patients receiving parenterally bridged warfarin. Rivaroxaban was associated with an average of 0.27-day shorter LOS, a 52% decreased odds of an encounter lasting >2 midnights and a $403 mean reduction in costs vs parenterally bridged warfarin (P≤.002 for all). The readmission rate for VTE during the same or subsequent 2 months following the index PE was similar between cohorts (P=.75). No patient in either cohort was readmitted for major bleeding. CONCLUSION: Rivaroxaban was associated with shortened LOS and lowered cost vs parenterally bridged warfarin in PE observation stay patients, without increases in the short-term rate of complications or readmission.

Is Rivaroxaban Associated With Shorter Hospital Stays and Reduced Costs Versus Parenteral Bridging to Warfarin Among Patients With Pulmonary Embolism?

OBJECTIVE: We sought to compare the length of stay (LOS) and total costs for patients with pulmonary embolism (PE) treated with either rivaroxaban or parenterally bridged warfarin. METHODS: This retrospective claims analysis was performed in the Premier Database from November 2012 to March 2015. Adult patients were included if they had a hospital encounter for PE (an International Classification of Diseases, Ninth Revision code = 415.1×) in the primary position, a claim for ≥1 diagnostic test for PE on day 0 to 2, and initiated rivaroxaban or parenteral anticoagulation/warfarin. Rivaroxaban users (allowing ≤2 days of prior parenteral therapy) were 1:1 propensity score matched to patients receiving parenterally bridged warfarin. Length of stay, total costs, and readmission for venous thromboembolism (VTE) or major bleeding during the same or subsequent 2 months following the index event were compared between cohorts. Analysis restricted to patients with low-risk PE was also performed. RESULTS: Characteristics of the matched PE cohorts (n = 3466 per treatment) were well balanced. Rivaroxaban use was associated with a 1.36-day shorter LOS and $2304 reduction in total costs compared to parenterally bridged warfarin ( P < .001 for both). Rates of readmission for VTE were similar between cohorts (1.7% vs 1.6%; P = .64). No difference was observed between treatments for readmission for major bleeding (0.2% vs 0.2%; P > .99). In analyses restricted to low-risk patients (n = 1551 per treatment), rivaroxaban was associated with a 1.01-day and a $1855 reduction in LOS and costs, respectively ( P < .001 for both). Rates of readmission were again similar between treatments ( P > .56 for all). CONCLUSION: Rivaroxaban significantly reduced hospital LOS and costs compared to parenterally bridged warfarin, without increasing the risk of readmission.

Pulmonary Embolism Inpatients Treated With Rivaroxaban Had Shorter Hospital Stays and Lower Costs Compared With Warfarin.

PURPOSE: Using real-world data, this study compares inpatient length of stay (LOS) and costs for patients with a primary diagnosis of pulmonary embolism (PE) initiating treatment with oral anticoagulation with rivaroxaban versus warfarin. METHODS: Hospitalizations from MarketScan's Hospital Drug Database were selected from November 1, 2012, through December 31, 2013, for adults with a primary diagnosis of PE initiating treatment with rivaroxaban or warfarin. Warfarin patients were matched 1:1 to rivaroxaban patients using exact and propensity score matching. Hospital LOS, treatment patterns, and hospitalization costs were evaluated. FINDINGS: Matched cohorts included 751 rivaroxaban-treated patients and 751 warfarin-treated patients. Adjusted mean LOS was 3.77 days for rivaroxaban patients (95% CI, 3.66-3.87 days) and 5.48 days for warfarin patients (95% CI, 5.33-5.63 days; P < .001). Mean (SD) LOS was shorter for patients taking rivaroxaban whether admission was for provoked PE (rivaroxaban: 5.2 [5.1] days; warfarin: 7.0 [6.5] days; P < .001) or unprovoked PE (rivaroxaban: 3.4 [2.3] days; warfarin: 5.1 [2.7] days; P < .001). Mean (SD) days from first dose to discharge were 2.5 (1.7) (rivaroxaban) and 4.0 (2.9) (warfarin) when initiated with parenteral anticoagulants (P < .001) and 2.7 (1.7) (rivaroxaban) and 4.0 (2.2) (warfarin) without parenteral anticoagulants (P < .001). The rivaroxaban cohort incurred significantly lower unadjusted mean (SD) hospitalization costs (rivaroxaban: $8473 [$9105]; warfarin: $10,291 [$9185]; P < .001), confirmed by covariate adjustment with generalized linear modeling estimating predicted mean hospitalization costs of $8266 for rivaroxaban patients (95% CI, $7851-$8681) and $10,511 for warfarin patients (95% CI, $10,031-$10,992; P < .001). IMPLICATIONS: patients with PE treated with rivaroxaban incurred significantly lower hospitalization costs by $2245 per admission compared with patients treated with warfarin, which was attributable to cost offsets from 1.71 fewer days of stay in the hospital.

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

BACKGROUND: 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. METHODS AND RESULTS: 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]). CONCLUSIONS: Rivaroxaban was associated with significantly shorter hospital LOS and lower hospitalization costs compared with warfarin.

Rivaroxaban versus Heparin Bridging to Warfarin Therapy: Impact on Hospital Length of Stay and Treatment Costs for Low-Risk Patients with Pulmonary Embolism.

STUDY OBJECTIVE: To compare hospital length of stay (LOS) and hospital treatment costs in low-risk patients with pulmonary embolism (PE) anticoagulated with rivaroxaban or heparin bridging to warfarin therapy. DESIGN: Retrospective review of electronic health records and hospital billing records. SETTING: Large, teaching hospital in the northeastern United States. PATIENTS: One hundred ninety adults with objectively confirmed acute PE presenting to the emergency department between November 1, 2012, and May, 12, 2015, who were classified as low risk of early mortality and received anticoagulation with either rivaroxaban or heparin (i.e., unfractionated heparin or low-molecular-weight heparin) bridging to warfarin therapy were included in the analysis. Patients were identified as low risk by at least one of the following prediction rules: simplified Pulmonary Embolism Severity Index (sPESI; 115 patients), Hestia criteria (87 patients), or In-hospital Mortality for Pulmonary Embolism using Claims Data (IMPACT; 108 patients); these were not mutually exclusive, as patients could be classified as low risk by more than one risk stratification tool. MEASUREMENTS AND MAIN RESULTS: We divided low-risk patients identified by each prediction rule into two cohorts: those receiving rivaroxaban (allowing ≤ 2 days of prior heparin use) or heparin bridging to warfarin therapy. The primary end points for this study were LOS (number of days from the patient's arrival at our institution until discharge) and total hospital treatment costs (our institution's actual costs to provide treatment) for the index PE hospital encounter. Using multivariable generalized linear model regression (gamma-distributed error and log-link), we estimated differences in LOS and hospital costs (in 2015 U.S. dollars) between the two cohorts after covariate adjustment. Rivaroxaban was associated with significantly shorter adjusted LOS (range -2.1 to -4.3 days) and significantly lower index hospital costs (range -$3835 to -$7094) versus heparin bridging to warfarin, regardless of the prediction rule used to identify low-risk patients. CONCLUSION: Among low-risk PE patients identified by using sPESI, Hestia or IMPACT, rivaroxaban was associated with significantly shorter LOS and lower hospital treatment costs versus heparin bridging to warfarin.

Hospital length of stay of nonvalvular atrial fibrillation patients who were administered Rivaroxaban versus Warfarin with and without pretreatment parenteral anticoagulants therapies.

BACKGROUND: Warfarin has been the only anticoagulant used for decades to prevent strokes and systemic embolisms in nonvalvular atrial fibrillation (NVAF) patients. Compared with rivaroxaban, warfarin has a narrow therapeutic range and many genetic and food-drug interactions that could potentially prolong hospital length of stay (LOS). OBJECTIVE: To compare hospital LOS between NVAF patients who were administered rivaroxaban versus warfarin with and without pretreatment of parenteral anticoagulant agents in a population of rivaroxaban-treated patients. METHODS: A retrospective matched-cohort analysis was conducted using the Premier Perspective Comparative Hospital Database from November 2010 to September 2012. Adult patients were included in the study if they had a hospitalization for NVAF. Rivaroxaban users were matched with up to 4 warfarin users based on propensity score analyses. Patients with and without pretreatment of parenteral anticoagulant agents were evaluated separately. Hospital LOS was compared between treatment groups using generalized estimating equations. RESULTS: The matched cohorts' characteristics were well balanced. Among the matched rivaroxaban and warfarin users who were administered parenteral agents, the mean age of the cohorts was 70 years and 47% of patients were female, whereas in the sample of patients who were not administered parenteral agents, the mean age was 72 years and 50% of patients were female. In the sample of patients who were administered parenteral agents, rivaroxaban users had significantly shorter hospital LOS (LOS difference: 1.38 days, P < 0.001) compared with warfarin users among rivaroxaban-treated patients. No significant difference in LOS was found in the sample of patients who were not administered parenteral anticoagulant agents (P = 0.169). CONCLUSION: In the study sample of NVAF patients who were administered parenteral anticoagulant agents, rivaroxaban was associated with a significantly shorter hospital LOS compared with warfarin. The difference in LOS was not statistically significant in the sample of patients who were not administered parenteral anticoagulant agents.

Anticoagulant use for the prevention of stroke in patients with atrial fibrillation: findings from a multi-payer analysis.

BACKGROUND: Oral anticoagulation is recommended for stroke prevention in intermediate/high stroke risk atrial fibrillation (AF) patients. The objective of this study was to demonstrate the usefulness of analytic software tools for descriptive analyses of disease management in atrial AF; a secondary objective is to demonstrate patterns of potential anticoagulant undertreatment in AF. METHODS: Retrospective data analyses were performed using the Anticoagulant Quality Improvement Analyzer (AQuIA), a software tool designed to analyze health plan data. Two-year data from five databases were analyzed: IMS LifeLink (IMS), MarketScan Commercial (MarketScanCommercial), MarketScan Medicare Supplemental (MarketScanMedicare), Clinformatics™ DataMart, a product of OptumInsight Life Sciences (Optum), and a Medicaid Database (Medicaid). Included patients were ≥ 18 years old with a new or existing diagnosis of AF. The first observed AF diagnosis constituted the index date, with patient outcomes assessed over a one year period. Key study measures included stroke risk level, anticoagulant use, and frequency of International Normalized Ratio (INR) monitoring. RESULTS: High stroke risk (CHADS2 ≥ 2 points) was estimated in 54% (IMS), 22% (MarketScanCommercial), 64% (MarketscanMedicare), 42% (Optum) and 62% (Medicaid) of the total eligible population. Overall, 35%, 29%, 38%, 39% and 16% of all AF patients received an anticoagulant medication in IMS, MarketScanCommercial, MarketScanMedicare, Optum and Medicaid, respectively. Among patients at high risk for stroke, 19% to 51% received any anticoagulant. CONCLUSIONS: The AQuIA provided a consistent platform for analysis across multiple AF populations with varying baseline characteristics. Analyzer results show that many high-risk AF patients in selected commercial, Medicare-eligible, and Medicaid populations do not receive appropriate thromboprophylaxis, as recommended by treatment guidelines.

Length of stay and economic consequences with rivaroxaban vs enoxaparin/vitamin K antagonist in patients with DVT and PE: findings from the North American EINSTEIN clinical trial program.

OBJECTIVE: Venous thromboembolism (VTE) (deep vein thrombosis [DVT] and pulmonary embolism [(PE]) represents a substantial economic burden to the healthcare system. Using data from the randomized EINSTEIN DVT and PE trials, this North American sub-group analysis investigated the potential of rivaroxaban to reduce the length of initial hospitalization in patients with acute symptomatic DVT or PE. METHODS: A post-hoc analysis of hospitalization and length-of-stay (LOS) data was conducted in the North American sub-set of patients from the randomized, open-label EINSTEIN trial program. Patients received either rivaroxaban (15 mg twice daily for 3 weeks followed by 20 mg once daily; n = 405) or dose-adjusted subcutaneous enoxaparin overlapping with (guideline-recommended 'bridging' therapy) and followed by a vitamin K antagonist (VKA) (international normalized ratio = 2.0-3.0; n = 401). The open-label study design allowed for the comparison of LOS between treatment arms under conditions reflecting normal clinical practice. LOS was evaluated using investigator records of dates of admission and discharge. Analyses were carried out in the intention-to-treat population using parametric tests. Costs were applied to the LOS based on weighted mean cost per day for DVT and PE diagnoses obtained from the Healthcare Cost and Utilization Project dataset. RESULTS: Of 382 patients hospitalized, 321 (84%), had acute symptomatic PE; few DVT patients required hospitalization. Similar rates of VTE patients were hospitalized in the rivaroxaban and enoxaparin/VKA treatment groups, 189/405 (47%) and 193/401 (48%), respectively. In hospitalized VTE patients, rivaroxaban treatment produced a 1.6-day mean reduction in LOS (median = 1 day) compared with enoxaparin/VKA (mean = 4.5 vs 6.1; median = 3 vs 4), translating to total costs that were $3419 lower in rivaroxaban-treated patients. CONCLUSION: In hospitalized North American patients with VTE, treatment with rivaroxaban produced a statistically significant reduction in LOS. When treating DVT and PE patients, clinicians should consider newer anti-coagulants with less complex treatment regimens.

Is rivaroxaban associated with lower inpatient costs compared to warfarin among patients with non-valvular atrial fibrillation?

BACKGROUND: Warfarin has been the mainstay treatment used by patients with a moderate-to-high risk of stroke due to non-valvular atrial fibrillation (NVAF). Unlike rivaroxaban, laboratory monitoring to allow the attainment of the prothrombin time international normalized ratio goal is required with warfarin, thereby potentially increasing a patient's hospitalization costs. OBJECTIVE: To compare hospitalization costs between hospitalized NVAF patients using rivaroxaban versus warfarin in a real-world setting. METHODS: A retrospective claims analysis was conducted using the Premier Perspective Comparative Hospital Database from November 2010 to September 2012. The study included adult patients hospitalized for NVAF after November 2011. Patients using rivaroxaban during hospitalization were matched with up to four warfarin users by propensity score analyses. Hospitalization costs were compared between the matched cohorts using generalized estimating equations. A sub-analysis was performed for patients who were first administered their treatment on day three or later of their hospital stay. Sensitivity analyses were conducted on matched cohorts with a primary diagnosis of AF. RESULTS: The matched cohorts' (2809 rivaroxaban and 11,085 warfarin users) characteristics were well balanced. The mean age of cohorts was 71 years and 49% of patients were female. The average hospitalization cost of rivaroxaban users was $11,993 compared to $13,255 for warfarin users. The cost difference was significantly lower by $1284 (P < 0.001). Patients who were administered rivaroxaban treatment on day three or after incurred significantly lower hospitalization costs (cost difference: $4350; P < 0.001) compared to warfarin users. Rivaroxaban users with a primary diagnosis of AF also had significantly lower costs compared to warfarin users. LIMITATIONS: These included possible inaccuracies or omissions in diagnoses, completeness of baseline characteristics, and a study population that included patients newly initiated on and patients who continued anticoagulant therapy. CONCLUSION: Hospitalization costs for rivaroxaban were significantly lower than those for warfarin in NVAF patients treated with rivaroxaban.

Hospital length of stay: is rivaroxaban associated with shorter inpatient stay compared to warfarin among patients with non-valvular atrial fibrillation?

BACKGROUND: Warfarin has been the mainstay treatment for prevention of stroke among patients with non-valvular atrial fibrillation (NVAF). Unlike rivaroxaban, warfarin requires laboratory monitoring to allow the attainment of the prothrombin time (PT) international normalized ratio (INR) goal, thereby potentially prolonging a patient's hospital length of stay (LOS). OBJECTIVE: To compare hospital LOS between hospitalized NVAF patients using rivaroxaban versus warfarin in a real-world setting. METHODS: A retrospective claims analysis was conducted using the Premier Perspective Comparative Hospital Database from 11/2010 to 9/2012. Adult patients were included in the study if they had a hospitalization for NVAF. Patients using rivaroxaban during hospitalization were matched with up to four warfarin users by propensity score analyses. Patients who were first administered their oral anticoagulants on day 3 or later of their hospital stay were also evaluated. Comparison of hospital LOS was assessed using generalized estimating equations. RESULTS: The characteristics of the matched cohorts were well balanced. Among the matched rivaroxaban and warfarin users (2809 and 11,085 patients, respectively), the mean age of the cohorts was 71 years and 49% of patients were female. The average (median) hospital LOS for rivaroxaban patients was 4.46 (3) days, compared to 5.27 (4) days for the warfarin cohort. The mean difference in hospital LOS of 0.81 days (19.44 hours) was found to be significant at P < 0.001. Patients who were administered rivaroxaban on day 3 of their hospital stay or later also had a significantly lower LOS compared to warfarin users. LIMITATIONS: These included inaccuracies or omissions in diagnoses, completeness of baseline characteristics, and a study population that included patients newly initiated on and patients who continued anticoagulant therapy. CONCLUSION: The study sample of NVAF patients receiving rivaroxaban was associated with a significantly shorter hospital length of stay compared to the sample of patients receiving warfarin.

One-year adherence to warfarin treatment for venous thromboembolism in high-risk patients and its association with long-term risk of recurrent events.

BACKGROUNDS: Warfarin is the predominant oral anticoagulant used for the prevention of recurrent venous thromboembolism (VTE) events. However, its long-term use is complicated by the need to manage the drug within a narrow therapeutic range and by possible food and drug interactions. OBJECTIVE: To examine the association between 1-year adherence, measured through compliance with and persistence on warfarin treatment for VTE, and long-term risk of recurrent events among patients at high risk. METHODS: Medical and pharmacy claims for patients with commercial or Medicare supplemental insurance in the Thomson Reuters MarketScan database were analyzed. Adult patients with medical claims with an associated VTE diagnosis between January 1, 2006, and March 31, 2008, were identified. The index date was defined as the date of the first observed VTE claim or the date of discharge if the index event was a hospital stay. High-risk patients (patients with cancer, or noncancer patients who did not have reversible risk factors during the 3-month period prior to the index date) who filled a warfarin prescription within 2 weeks of the index date were included. Persistence was evaluated in terms of discontinuation, defined as a 90-day gap in warfarin supply during a 1-year assessment period following the index date. Compliance was measured by the proportion of days covered (PDC) over the 1-year assessment period, with PDC less than 0.8 defined as noncompliance. Recurrent VTE events were identified as hospitalizations where VTE was the primary diagnosis after the 1-year assessment period and until patients were lost to follow-up. The association between adherence to warfarin therapy and VTE recurrence was evaluated descriptively via Kaplan-Meier curves and a Cox proportional hazards model, adjusted for patient demographic and clinical characteristics. A similar analysis using the medication possession ratio (MPR) as a measure of compliance was also performed in a subset of patients who had filled at least 2 warfarin prescriptions. RESULTS: The study included 8,040 VTE patients identified as being at high risk of recurrence (mean age 61 years, 59.4% male), of whom 76.9% were not compliant with warfarin therapy based on PDC, and 51.5% discontinued therapy. Among those with at least 2 warfarin prescriptions (n = 7612), 34.1% of high-risk patients were not compliant with warfarin therapy between the first and last refills based on MPR. Kaplan-Meier curves showed that patients who were compliant or continued warfarin therapy were less likely to experience a VTE event (all P less than 0.05). Noncompliant patients had a 3 times greater risk of VTE recurrence than compliant patients, based on PDC (hazard ratio [HR] = 3.01, 95% confidence interval [CI]: 1.28-4.97). Among the subpopulation who filled at least 2 warfarin prescriptions, noncompliant patients (based on MPR) were also found to be more likely to have recurrent VTE events, compared with compliant patients (HR = 1.60, 95% CI: 1.18-2.16). Patients who discontinued warfarin were more likely to have recurrent VTE events compared with patients who did not discontinue on warfarin treatment (HR = 1.48, 95% CI: 1.09-2.01). CONCLUSION: Adherence to a year of therapy was low in patients at high risk of recurrent VTE, even though long-term therapy should be considered in this population. Noncompliance and discontinuation of warfarin treatment over a 1-year period was associated with a higher risk of recurrent VTE. Future research should investigate and differentiate between patient and provider discontinuation to develop strategies to improve compliance and persistence with appropriate anticoagulation therapy that may potentially reduce recurrent VTE.

Hospital visits and costs following outpatient treatment of CAP with levofloxacin or moxifloxacin.

BACKGROUND: Hospital admissions (inpatient and emergency room) are a major source of medical costs for community-acquired pneumonia (CAP) initially treated in the outpatient setting. Current CAP treatment guidelines do not differentiate between outpatient treatment with levofloxacin and moxifloxacin. OBJECTIVE: Compare health care resource use and medical costs to payers for CAP outpatients initiating treatment with levofloxacin or moxifloxacin. RESEARCH DESIGN AND METHODS: CAP episodes were identified in the PharMetrics database between 2Q04 and 2Q07 based on: pneumonia diagnosis, chest X-ray and treatment with levofloxacin or moxifloxacin. Subsequent 30-day risk of pneumonia-related hospital visits and 30-day health care costs to payers for levofloxacin vs. moxifloxacin treatment were estimated after adjusting for pre-treatment demographics, health care resource use and pneumonia-specific risk factors using propensity score and exact factor matching. RESULTS: A total of 15,472 levofloxacin- and 6474 moxifloxacin-initiated CAP patients were identified. Among 6352 matched pairs, levofloxacin treatment was associated with a 35% reduction in the odds of pneumonia-related hospital visits (odds ratio = 0.65, P = 0.004), lower per-patient costs for pneumonia-related hospital visits (102 dollars vs. 210 dollars, P = 0.001), lower pneumonia-related total costs (medical services and prescription drugs, 363 dollars vs. 491 dollars, P < 0.001) and lower total costs (1308 dollars vs. 1446 dollars, P < 0.001) vs. moxifloxacin over the 30-day observation period. LIMITATIONS: Although observational analyses of claims data provide large sample sizes and reflect routine care, they do have several inherent limitations. Since randomization of subjects is not possible, adequate statistical techniques must be used to ensure that patient characteristics are well-balanced between treatment groups. In addition, data may be missing or miscoded. CONCLUSIONS: CAP outpatients initiated with levofloxacin generated substantially lower costs to payers compared to matched patients initiated with moxifloxacin. The cost savings for patients initiated with levofloxacin were largely attributable to reduced rates of pneumonia-related hospitalization or ER visits.

A comparison of levofloxacin and moxifloxacin use in hospitalized community-acquired pneumonia (CAP) patients in the US: focus on length of stay.

OBJECTIVE: Length of stay (LOS) and hospitalization costs were compared among patients admitted for community-acquired pneumonia (CAP) and initially treated with either levofloxacin 750 mg intravenous (IV) or with moxifloxacin 400 mg IV. Hospital-related complications and relationship of LOS and comorbidities were descriptively examined. METHODS: A retrospective database study was conducted of adult patients admitted for CAP and given levofloxacin 750 mg IV or moxifloxacin 400 mg IV through the first 3 days of hospitalization, using the Premier Perspective comparative database. Cohorts were matched 1:1 by hospital geographic location, by coarse caliper propensity scores using all baseline covariates, and by Mahalanobis metric matching based on age and severity (All Patient Refined-Diagnosis-related Groups Severity of Illness (APR-DRG SOI) index). Comparisons between groups were further adjusted for characteristics that remained imbalanced after matching using generalized estimating equation methodology. RESULTS: The initial sample of 3868 patients (levofloxacin = 827; moxifloxacin = 3041) was reduced to 1594 (797 patients per treatment group) after matching. Analyses of matched cohorts showed that the mean hospital LOS was significantly shorter for patients treated with levofloxacin 750 mg IV than for those patients treated with moxifloxacin 400 mg IV (5.8 vs. 6.4 days, respectively; least squares mean difference = 0.54 days; p = 0.020). Hospitalization costs were also lower for the levofloxacin 750 mg IV-treated patients (least squares mean difference = US$129; p = 0.753). There were no significant differences in the percentage of patients experiencing complications. LIMITATIONS: Although claims databases provide large sample sizes and reflect routine care, they do have several inherent limitations. Since randomization of subjects is not possible, adequate statistical techniques must be used to ensure treatment groups are balanced with respect to patient and clinical characteristics. In addition, data may be missing or miscoded. CONCLUSIONS: This retrospective study suggests that among patients hospitalized with CAP, initial treatment with levofloxacin 750 mg IV is associated with a significantly shorter mean hospital LOS compared with treatment with moxifloxacin 400 mg IV. The clinical implications of a shorter hospital LOS include improved patient and economic outcomes.