National and Local Direct Medical Cost Burden of COPD in the United States From 2016 to 2019 and Projections Through 2029.

BACKGROUND: Despite the significant burden posed by COPD to health care systems, there is a lack of up-to-date information quantifying the general COPD burden, costs, and long-term projections to various stakeholders in the United States. RESEARCH QUESTION: What are the updated state-specific and nationwide estimates of the COPD disease burden and direct costs in 2019, along with projections of COPD-attributable medical costs through 2029? STUDY DESIGN AND METHODS: A cross-sectional, retrospective study design using the 2016 to 2019 Medical Expenditure Panel Survey, 2019 American Community Survey, and 2019 Behavioral Risk Factor Surveillance System data was applied to generate COPD-attributable expenditure estimates. Cost projections for the years 2020 to 2029 were based on 2017 national population projections reported by the US Census Bureau, and all costs were adjusted to 2019 US dollars. RESULTS: In total, 4,135 people living with COPD were included; a higher proportion had other concurrent conditions such as cardiovascular-related conditions compared with people without COPD (n = 86,021). Overall, in 2019, COPD-attributable medical costs after adjusting for demographic characteristics and 19 concurrent conditions (including COPD-related and non-COPD-related conditions) were estimated at $31.3 billion, with state-specific cost estimates reporting wide variation, from $44.8 million in Alaska to $3.1 billion in Florida. Nationwide COPD-attributable medical costs borne by payer type were as follows: private insurance, $11.4 billion; Medicare, $10.8 billion; and Medicaid, $3.0 billion. Projections of national medical costs attributable to COPD are reported to increase to $60.5 billion in 2029. INTERPRETATION: Understanding the current disease and economic burden of COPD in the United States, along with the projected costs attributable to COPD in the next decade, will highlight unmet needs and gaps in care that help inform health care decision-makers in planning future actions to alleviate this disease burden.

Risk of stroke/systemic embolism, major bleeding, and associated costs in non-valvular atrial fibrillation patients who initiated apixaban, dabigatran, or rivaroxaban compared with warfarin in the United States medicare population: updated analysis.

OBJECTIVE: To provide an updated comparison of the risk and cost of stroke/systemic embolism (SE) and major bleeding between direct oral anticoagulants (DOAC: apixaban, rivaroxaban, dabigatran) and warfarin among non-valvular atrial fibrillation (NVAF) patients. METHODS: Adults (≥65 years) initiating warfarin or DOACs between 1 January 2013 and 31 December 2014 were selected from the Medicare database and propensity scores matched 1:1 to balance baseline characteristics. Cox proportional hazards models were used to estimate the risks of stroke/SE and major bleeding of each DOAC vs. warfarin. Two-part models were used to compare the stroke/SE- and major bleeding-related medical costs in each matched cohort. RESULTS: Of the 264,479 eligible patients, 38,740 apixaban-warfarin pairs, 76,677 rivaroxaban-warfarin pairs, and 20,955 dabigatran-warfarin pairs were matched. Apixaban (Hazard Ratio [HR] = 0.46; 95% Confidence Interval [CI] 0.38-0.56) and rivaroxaban (HR = 0.71; 95% CI 0.63-0.80) were associated with a significantly lower risk of stroke/SE compared to warfarin. Apixaban (HR = 0.57; 95% CI 0.51-0.63) and dabigatran (HR = 0.80; 95% CI 0.70-0.90) were associated with a significantly lower risk of major bleeding; rivaroxaban (HR = 1.14; 95% CI 1.07-1.21) was associated with a significantly higher risk of major bleeding compared to warfarin. Compared to warfarin, apixaban and rivaroxaban had significantly lower stroke/SE-related medical costs; and apixaban and dabigatran had significantly lower major bleeding-related medical costs. CONCLUSIONS: This real-world analysis showed DOACs to be associated with a lower risk of stroke/SE and major bleeding, and lower medical costs compared to warfarin. Among them, only apixaban appears to be associated with a significantly lower risk of all three outcomes collectively: stroke/SE, major bleeding, and lower related medical costs compared to warfarin.

Patterns of use and outcomes of peripherally inserted central catheters in hospitalized patients with solid tumors: A multicenter study.

BACKGROUND: The risk of peripherally inserted central catheter (PICC)-related complications in patients hospitalized with solid tumors remains unclear. Existing studies are limited by single-center, outpatient designs and include heterogenous patients. METHODS: A retrospective cohort study was designed and included adult patients with solid organ cancers who were admitted to a general medicine ward or intensive care unit and received a PICC. Data were collected from November 2013 to December 2019 at 50 Michigan hospitals. Major complications were defined as central line-associated bloodstream infection, deep vein thrombosis, pulmonary embolism, and catheter occlusion. Hospital variation in PICC use and outcomes was examined. RESULTS: Data included 3235 hospitalized patients with solid tumors who had PICCs placed for 51,047 catheter days. Most catheters were double-lumen devices (57.0%). Notably, 17.5% of patients had another central venous catheter at the time of PICC insertion. The most common indications for PICC use were antibiotics (34.5%) and difficult access or blood draws (21.6%); chemotherapy was the primary indication in only 15.7% of patients. A major PICC-related complication occurred in 491 patients (15.2%); catheter occlusion was the most prevalent complication (n = 322; 10.0%) followed by deep vein thrombosis (n = 116; 3.6%), central line-associated bloodstream infection (n = 82; 2.5%), and pulmonary embolism (n = 20; 0.6%). Significant variation in indications for PICC use, device characteristics, and frequency of major complications across hospitals was observed (p < .001). CONCLUSIONS: PICCs were associated with significant complications in hospitalized patients who had solid malignancies and were often used for reasons other than chemotherapy. Policies and guidance for the appropriate use of PICCs in oncologic patients appear necessary. LAY SUMMARY: Peripherally inserted central catheters (PICCs) are devices placed in peripheral veins to deliver medication to large veins near the heart. PICCs are used frequently in oncology. The objective of this report was to describe PICC-associated complications in hospitalized patients with solid tumors. This study was performed across 50 Michigan hospitals and included 3235 patients with solid tumor cancers and who had a PICC. Overall, 15.2% of patients experienced a complication, including central line-associated bloodstream infections, deep vein thrombosis, pulmonary embolism, or catheter occlusion. Complication rates varied across hospitals. PICCs are associated with substantial complications in hospitalized patients with solid tumors.

Overdiagnosis of urinary tract infection linked to overdiagnosis of pneumonia: a multihospital cohort study.

Urinary tract infection (UTI) and community-acquired pneumonia (CAP) are the most common infections treated in hospitals. UTI and CAP are also commonly overdiagnosed, resulting in unnecessary antibiotic use and diagnostic delays. While much is known individually about overdiagnosis of UTI and CAP, it is not known whether hospitals with higher overdiagnosis of one also have higher overdiagnosis of the other. Correlation of overdiagnosis of these two conditions may indicate underlying hospital-level contributors, which in turn may represent targets for intervention. To evaluate the association of overdiagnosis of UTI and CAP, we first determined the proportion of hospitalised patients treated for CAP or UTI at 46 hospitals in Michigan who were overdiagnosed according to national guideline definitions. Then, we used Pearson's correlation coefficient to compare hospital proportions of overdiagnosis of CAP and UTI. Finally, we assessed for 'diagnostic momentum' (ie, accepting a previous diagnosis without sufficient scepticism) by determining how often overdiagnosed patients remained on antibiotics on day 3 of hospitalisation. We included 14 085 patients treated for CAP (11.4% were overdiagnosed) and 10 398 patients treated for UTI (27.8% were overdiagnosed) across 46 hospitals. Within hospitals, the proportion of patients overdiagnosed with UTI was moderately correlated with the proportion of patients overdiagnosed with CAP (r=0.53, p<0.001). Over 80% (81.8% (n=952/1164) of UTI; 89.9% (n=796/885) of CAP) of overdiagnosed patients started on antibiotics by an emergency medicine clinician remained on antibiotics on day 3 of hospitalisation. In conclusion, we found overdiagnosis of UTI and CAP to be correlated at the hospital level. Reducing overdiagnosis of these two common infections may benefit from systematic interventions.

Patterns of vascular access device use and thrombosis outcomes in patients with COVID-19: a pilot multi-site study of Michigan hospitals.

Venous thromboembolism (VTE) is an important complication of coronavirus disease 2019 (COVID-19). To date, few studies have described vascular access device use and VTE risk in this cohort. To examine the use of vascular access devices and incidence of VTE in patients hospitalized with COVID-19. We performed a retrospective, multi-center cohort study of patients hospitalized with COVID-19 who received a midline catheter, peripherally inserted central catheter (PICCs), tunneled or non-tunneled central venous catheter (CVC), hemodialysis (HD) catheter or a port during hospitalization. Mixed-effects multivariable logit models adjusting for VTE risk factors in the Caprini risk score were fit to understand the incremental risk of VTE in patients with vascular access devices vs. those that did not receive devices. Management of VTE was determined by examining anticoagulant use pre- vs. post-thrombosis. Results were expressed using odds ratios (ORs) and associated 95% confidence intervals (CI). A total of 1228 hospitalized COVID-19 patients in 40 hospitals, of which 261 (21.3%) received at least one vascular access device of interest, were included. The prevalence of acute, non-tunneled CVCs was 42.2%, acute HD catheters 18.4%, midline catheters 15.6%, PICCs 15.6%, tunneled CVCs 6.8%, and implanted ports 1.4%. The prevalence of VTE was 6.0% in the study cohort, and 10.0% among patients with vascular access devices. After adjusting for known VTE risk factors, patients that had a vascular access device placed were observed to have a four-fold greater odds of VTE than those that did not (OR 4.17, 95% CI 2.33-7.46). Patients who received multiple different catheters experienced more VTE events compared with patients that received only one type (21.5% vs. 6.1%, p < .001). Among the 26 patients with VTE, only 8 (30.8%) survived to discharge and among these, only 5 were discharged on therapeutic doses of anticoagulation. Hospitalized patients with COVID-19 that receive vascular access devices experienced higher rates of VTE than those that do not. Future studies to evaluate the nexus between COVID-19, vascular device use, and thrombosis appear are warranted.

Safety and Outcomes of Midline Catheters vs Peripherally Inserted Central Catheters for Patients With Short-term Indications: A Multicenter Study.

Importance: Peripherally inserted central catheters (PICCs) and midlines are frequently used for short-term venous access; whether one is safer than the other in this setting has not been adequately reported. Objective: To compare outcomes between patients who had a PICC vs midline placed for the indication of difficult vascular access or antibiotic therapy for 30 or fewer days. Design, Setting, and Participants: This cohort study analyzed data from a multihospital registry including patients admitted to a participating site from December 2017 through January 2020 who had a PICC or midline placement for the indications of difficult venous access or intravenous antibiotic therapy prescribed for 30 or fewer days. Data were analyzed from October 2020 to March 2021. Exposures: PICC and midline placement. Main Outcomes and Measures: Major complications, including a composite of symptomatic catheter-associated deep vein thrombosis (DVT), catheter-related bloodstream infection, and catheter occlusion. Logistic regression and Cox proportional hazards regression models (taking into account catheter dwell) were used to estimate risk for major complications, adjusting for patient and device characteristics and the clustered nature of the data. Sensitivity analyses limiting analyses to 10 days of device dwell were performed. Results: Data on 10 863 patients, 5758 with PICCs and 5105 with midlines (median [IQR] age of device recipients, 64.8 [53.4-75.4] years; 5741 [52.8%] were female), were included. After adjusting for patient characteristics, comorbidities, catheter lumens, and dwell time in logit models, patients who received PICCs had a greater risk of developing a major complication compared with those who received midlines (odds ratio, 1.99; 95% CI, 1.61-2.47). Reduction in complications stemmed from lower rates of occlusion (2.1% vs 7.0%; P < .001) and bloodstream infection (0.4% vs 1.6%; P < .001) in midlines vs PICCs; no significant difference in the risk of DVT between PICCs and midlines was observed. In time-to-event models, similar outcomes for bloodstream infection and catheter occlusion were noted; however, the risk of DVT events was lower in patients who received PICCs vs midlines (hazard ratio, 0.53; 95% CI, 0.38-0.74). Results were robust to sensitivity analyses. Conclusions and Relevance: In this cohort study among patients with placement of midline catheters vs PICCs for short-term indications, midlines were associated with a lower risk of bloodstream infection and occlusion compared with PICCs. Whether DVT risk is similar or greater with midlines compared with PICCs for short-term use is unclear. Randomized clinical trials comparing these devices for this indication are needed.

Improving peripherally inserted central catheter appropriateness and reducing device-related complications: a quasiexperimental study in 52 Michigan hospitals.

BACKGROUND: The Michigan Appropriateness Guide for Intravenous Catheters (MAGIC) provides evidence-based criteria for peripherally inserted central catheter (PICC) use. Whether implementing MAGIC improves PICC appropriateness and reduces complications is unknown. METHODS: A quasiexperimental study design to implement MAGIC in 52 Michigan hospitals was used. Data were collected from medical records by trained abstractors. Hospital performance on three appropriateness criteria was measured: short-term PICC use (≤5 days), use of multilumen PICCs and PICC placement in patients with chronic kidney disease. PICC appropriateness and device complications preintervention (January 2013 to December 2016) versus postintervention (January 2017 to January 2020) were compared. Change-point analysis was used to evaluate the effect of the intervention on device appropriateness. Logistic regression and Poisson models were fit to assess the association between appropriateness and complications (composite of catheter occlusion, venous thromboembolism (VTE) and central line-associated bloodstream infection (CLABSI)). RESULTS: Among 38 592 PICCs, median catheter dwell ranged from 8 to 56 days. During the preintervention period, the mean frequency of appropriate PICC use was 31.9% and the mean frequency of complications was 14.7%. Following the intervention, PICC appropriateness increased to 49.0% (absolute difference 17.1%, p<0.001) while complications decreased to 10.7% (absolute difference 4.0%, p=0.001). Compared with patients with inappropriate PICC placement, appropriate PICC use was associated with a significantly lower odds of complications (OR 0.29, 95% CI 0.25 to 0.34), including decreases in occlusion (OR 0.25, 95% CI 0.21 to 0.29), CLABSI (OR 0.61, 95% CI 0.46 to 0.81) and VTE (OR 0.40, 95% CI 0.33 to 0.47, all p<0.01). Patients with appropriate PICC placement had lower rate of complications than those with inappropriate PICC use (incidence rate ratio 0.987, 95% CI 0.98 to 0.99, p<0.001). CONCLUSIONS: Implementation of MAGIC in Michigan hospitals was associated with improved PICC appropriateness and fewer complications. These findings have important quality, safety and policy implications for hospitals, patients and payors.

Antibiotic overuse after discharge from medical short-stay units.

Of 100 patients discharged from short-stay units (SSUs) with antibiotics, 47 had a skin and soft-tissue infection, 22 had pneumonia, and 21 had a urinary tract infection. Among all discharge antibiotic prescriptions, 78% involved antibiotic overuse, most commonly excess duration (54 of 100) and guideline discordant selection (44 of 100).

Comparison of incidence/occurrence of cardiovascular events between ponatinib vs bosutinib among patients with at least one prior line of tyrosine kinase inhibitors in chronic myeloid leukemia in a community setting in the United States.

INTRODUCTION: In this real-world study, the incidence of cardiovascular events (CV) including major adverse cardiac events (MACE), arterial occlusive events (AOE), and venous occlusive events (VOE) was evaluated in chronic myeloid leukemia (CML) patients treated with ponatinib or bosutinib in a US commercial database population. MATERIALS AND METHODS: CML patients aged ≥18 years with use of 1 or 2 prior tyrosine kinase inhibitors prescribed bosutinib or ponatinib were selected from the IBM® MarketScan® Research database. Cox proportional hazard model analyses were conducted to examine any difference in CV event risk. RESULTS: Ponatinib and bosutinib was associated with similar incidence and risk of CV events, including MACEs (HR: 1.02; 95% CI: 0.35, 3.01), AOEs (HR: 0.90; 95% CI: 0.43, 1.85) and VOEs (HR: 0.92; 95% CI: 0.44, 1.94). CONCLUSION: Treatment with ponatinib or bosutinib was not associated with significant differences in the incidence of CV events in CML patients.

Impact of Inpatient Attending Specialty and Gastroenterology Consultation on Quality of Care of Patients Hospitalized with Decompensated Cirrhosis.

BACKGROUND: Data suggest hospitalists are less adherent to quality indicators for decompensated cirrhosis, and gastroenterology consultation may improve adherence. We sought to evaluate the impact of inpatient attending specialty and gastroenterology consultation on quality of care for decompensated cirrhosis. METHODS: This was a retrospective cohort study of patients with decompensated cirrhosis admitted to gastroenterology or hospitalist service at the University of Michigan between 2016-2020. The primary outcome was adherence to nationally recommended inpatient quality indicators for ascites, hepatic encephalopathy, spontaneous bacterial peritonitis, and gastrointestinal bleeding. Performance was calculated per patient admission as the proportion of quality indicators met vs quality indicators for which the patient was eligible. Quality indicator scores were compared between services using t-tests. We also evaluated the effect of gastroenterology consultation on quality indicator scores for patients admitted to hospitalist service. Clinical outcomes were compared using multivariable models adjusted for patient characteristics. RESULTS: Two hundred eighty-eight admissions were included (155 to gastroenterology service; 133 to hospitalist service). Quality indicator score for all admissions was 69.9% (standard deviation [SD] ± 24.2%). Quality indicator scores were similar between gastroenterology (69.9%, SD ± 23.6%) and hospitalist (69.8%, SD ± 25.1%) services (P = .913). There was no difference in quality indicator subscores for each complication between services. Hospitalists placed a gastroenterology consultation in 53.4% of admissions, and it was associated with higher albumin administration for patients with spontaneous bacterial peritonitis (57.1% vs 25%, P = .044). Patients admitted to gastroenterology service had higher readmissions within 30 days (adjusted odds ratio = 1.95) and shorter length of hospitalization (adjusted rate ratio = 0.85). CONCLUSIONS: Hospitalists provided comparable quality of care to gastroenterologists for inpatients with decompensated cirrhosis.

The Impact of Intestinal Complications on Health Care Costs Among Patients With Inflammatory Bowel Disease Treated With Anti-Tumor Necrosis Factor Therapies.

BACKGROUND: Although there is evidence that anti-tumor necrosis factor (TNF) utilization earlier in the inflammatory bowel disease (IBD) course and before the onset of disease-related complications leads to improved patient outcomes, the health care costs and utilization impact have not been well defined. This study assessed differences in health care utilization and costs among patients with IBD treated with anti-TNFs. METHODS: Patients with a diagnosis of ulcerative colitis (UC) or Crohn disease (CD) between January 1, 2001, and December 31, 2014, were identified from a claims database. Patients were required to have ≥1 claim for a 5-aminosalicylic acid, corticosteroid, or immunomodulator after the IBD diagnosis and ≥1 anti-TNF drug claim after the first IBD treatment. Complication and noncomplication cohorts were identified based on disease-related complications and IBD-related hospitalizations or emergency department visits for 6 months before anti-TNF initiation. Generalized linear models were used to compare health care costs and utilization for the 12 months after anti-TNF initiation (follow-up). RESULTS: The study included 6329 patients with CD and 4451 patients with UC. In patients with CD with complications, >33.7% had intestinal strictures and 6% had enteroenteric fistula before anti-TNF treatment. Patients with CD with complications incurred significantly higher IBD-related and all-cause health care costs during follow-up, and patients with UC experienced the same trends. CONCLUSIONS: These results suggest that anti-TNF treatment after, rather than before, a patient develops complications leads to a higher economic burden. However, these findings could also result from patients with more severe disease having early complications that are more difficult to treat.

A Real-World Observational Study of Hospitalization and Health Care Costs Among Nonvalvular Atrial Fibrillation Patients Prescribed Oral Anticoagulants in the U.S. Medicare Population.

This article has been corrected. Please see J Manag Care Spec Pharm, 2020;26(5):682 BACKGROUND: Clinical trials have shown that direct oral anticoagulants (DOACs)-including dabigatran, rivaroxaban, apixaban, and edoxaban-are at least as effective and safe as warfarin for the risk of stroke/systemic embolism (SE) and major bleeding (MB) in patients with atrial fibrillation (AF). However, few studies have compared oral anticoagulants (OACs) among elderly patients. OBJECTIVE: To compare hospitalization risks (all-cause, stroke/SE-related, and MB-related) and associated health care costs among elderly nonvalvular AF (NVAF) patients in the Medicare population who initiated warfarin, dabigatran, rivaroxaban, or apixaban. METHODS: Patients (aged ≥ 65 years) initiating warfarin or DOACs (apixaban, rivaroxaban, and dabigatran) were selected from the Centers for Medicare & Medicaid Services database from January 1, 2013, to December 31, 2014. Patients initiating each OAC were matched 1:1 to apixaban patients using propensity score matching to balance demographic and clinical characteristics. Cox proportional hazards models were used to estimate the risk of hospitalization of each OAC versus apixaban. Generalized linear models and two-part models with bootstrapping were used to compare all-cause health care costs and stroke/SE- and MB-related medical costs between matched cohorts. RESULTS: Of the 264,479 eligible patients, 77,480 warfarin-apixaban, 41,580 dabigatran-apixaban, and 77,640 rivaroxaban-apixaban patients were matched. The OACs were associated with a significantly higher risk of all-cause hospitalization compared with apixaban (warfarin: HR = 1.27, 95% CI = 1.23-1.31, P < 0.001; dabigatran: HR = 1.13, 95% CI = 1.08-1.18, P < 0.001; and rivaroxaban: HR = 1.22, 95% CI = 1.18-1.26, P < 0.001) and were associated with a significantly higher risk of hospitalization due to stroke/SE (warfarin: HR = 2.18, 95% CI = 1.80-2.64, P < 0.001; dabigatran: HR = 1.45, 95% CI = 1.12-1.88, P = 0.006; and rivaroxaban: HR = 1.40, 95% CI = 1.14-1.71, P = 0.001). Also, the OACs were associated with significantly higher risk of hospitalization due to MB-related conditions compared with apixaban (warfarin: HR = 1.76, 95% CI = 1.59-1.95, P < 0.001; dabigatran: HR = 1.44, 95% CI = 1.23-1.68, P < 0.001; and rivaroxaban: HR = 1.89, 95% CI = 1.71-2.09, P < 0.001). Compared with apixaban, warfarin ($3,577 vs. $3,183, P < 0.001); dabigatran ($3,217 vs. $3,060, P < 0.001); and rivaroxaban ($3,878 vs. $3,180, P < 0.001) had significantly higher all-cause total health care costs per patient per month. Patients initiating the OACs had significantly higher MB-related medical costs compared with apixaban: warfarin ($472 vs. $269; P < 0.001); dabigatran ($364 vs. $245, P < 0.001); and rivaroxaban ($493 vs. $270, P < 0.001). Warfarin was also associated with higher stroke/SE-related medical costs compared with apixaban ($124 vs. $62, P < 0.001). CONCLUSIONS: This real-world study showed that among elderly NVAF patients in the Medicare population, apixaban was associated with significantly lower risks of all-cause, stroke/SE-related, and MB-related hospitalizations compared with warfarin, dabigatran, and rivaroxaban. Accordingly, apixaban showed significantly lower all-cause health care costs and MB-related medical costs. DISCLOSURES: This study was funded by Bristol Myers Squibb and Pfizer. Amin is an employee of the University of California, Irvine, and was a paid consultant to Bristol Myers Squibb in connection with this study and the development of this manuscript. He has served as a consultant and/or speaker for Bristol Myers Squibb, Pfizer, and Boehringer Ingelheim. Keshishian and Zhang are employees of STATinMED Research, a paid consultant to Pfizer and Bristol Myers Squibb in connection with this study and the development of this manuscript. Trocio, Dina, Mardekian, and Liu are employees of Pfizer, with ownership of stocks in Pfizer. Le, Rosenblatt, Nadkarni, and Vo are employees of Bristol Myers Squibb. Rosenblatt and Vo have ownership of stocks in Bristol Myers Squibb. Baser has no conflicts to disclose.

Effectiveness and safety of direct oral anticoagulants compared to warfarin in treatment naïve non-valvular atrial fibrillation patients in the US Department of defense population.

BACKGROUND: Clinical trials have demonstrated that direct oral anticoagulants (DOACs) are at least non-inferior to warfarin in reducing the risk of stroke/systemic embolism (SE) among patients with non-valvular atrial fibrillation (NVAF), but the comparative risk of major bleeding varies between DOACs and warfarin. Using US Department of Defense (DOD) data, this study compared the risk of stroke/SE and major bleeding for DOACs relative to warfarin. METHODS: Adult patients with ≥1 pharmacy claim for apixaban, dabigatran, rivaroxaban, or warfarin from 01 Jan 2013-30 Sep 2015 were selected. Patients were required to have ≥1 medical claim for atrial fibrillation during the 12-month baseline period. Patients with a warfarin or DOAC claim during the 12-month baseline period were excluded. Each DOAC cohort was matched to the warfarin cohort using propensity score matching (PSM). Cox proportional hazards models were conducted to evaluate the risk of stroke/SE and major bleeding of each DOAC vs warfarin. RESULTS: Of 41,001 identified patients, there were 3691 dabigatran-warfarin, 8226 rivaroxaban-warfarin, and 7607 apixaban-warfarin matched patient pairs. Apixaban was the only DOAC found to be associated with a significantly lower risk of stroke/SE (hazard ratio [HR]: 0.55; 95% confidence interval [CI]: 0.39, 0.77; p < 0.001) and major bleeding (HR: 0.65; 95% CI: 0.53, 0.80; p < 0.001) compared to warfarin. Dabigatran and rivaroxaban initiation were associated with similar risk of stroke/SE (dabigatran: HR: 0.68; 95% CI: 0.43, 1.07; p = 0.096; rivaroxaban: HR: 0.83; 95% CI: 0.64, 1.09; p = 0.187) and major bleeding (dabigatran: HR: 1.05; 95% CI: 0.79, 1.40; p = 0.730; rivaroxaban: HR: 1.07; 95% CI: 0.91, 1.27; p = 0.423) compared to warfarin. CONCLUSION: Among NVAF patients in the US DOD population, apixaban was associated with significantly lower risk of stroke/SE and major bleeding compared to warfarin. Dabigatran and rivaroxaban were associated with similar risk of stroke/SE and major bleeding compared to warfarin.

Treatment Patterns, Healthcare Resource Utilization and Costs Among Schizophrenia Patients Treated with Long-Acting Injectable Versus Oral Antipsychotics.

INTRODUCTION: Long-acting injectable (LAI) antipsychotic use may reduce healthcare resource utilization compared with oral antipsychotic use by improving adherence and reducing dosing frequency. Our goal was to examine treatment patterns, healthcare utilization, and costs among recently diagnosed schizophrenia patients receiving oral versus LAI antipsychotics. METHODS: The MarketScan Multi-state Medicaid database was used to identify schizophrenia patients aged ≥ 18 years who received an LAI or oral antipsychotic between January 1, 2011 and December 31, 2014. Primary outcomes included treatment patterns such as adherence (measured as proportion of days covered-PDC), persistence, discontinuation, switching, and healthcare resource utilization and costs. Propensity score matching (PSM) was used to control for differences in baseline characteristics between the cohorts. Outcomes were assessed over a 12-month post-index period and compared between treatment cohorts. RESULTS: After PSM, 2302 patients were included in each of the LAI and oral antipsychotics cohorts. There were no differences in PDC or therapy switching between the two cohorts. Compared with the oral cohort, patients receiving LAIs had lower discontinuation rates (46.1 vs. 61.6%, p < 0.001), fewer inpatient admissions (0.5 vs. 0.9, p < 0.001), hospital days (3.9 vs. 6.5, p < 0.001), and ER visits (2.4 vs. 2.9, p = 0.007), and a higher number of prescription fills (29.5 vs. 25.3, p < 0.001). Patients prescribed LAIs had lower monthly inpatient ($US4007 vs. 8769, p < 0.001) and ER visits costs ($682 vs. 891, p < 0.001) but higher monthly medication costs ($10,713 vs. $655, p < 0.001) compared with the oral cohort over the 12-month post-index period. Overall, both cohorts had similar total medical costs (LAI vs. oral: $24,988 vs. 23,887, p = 0.354) during the follow-up period. CONCLUSION: Patients receiving LAIs were more likely to remain on medication compared with the oral group, which may account for reduced inpatient admissions. Hospitalization cost reductions offset the higher costs of LAI medications, resulting in no increase in total healthcare costs relative to oral antipsychotic use. FUNDING: Alkermes Inc.

Real-World Comparative Effectiveness, Safety, and Health Care Costs of Oral Anticoagulants in Nonvalvular Atrial Fibrillation Patients in the U.S. Department of Defense Population.

BACKGROUND: The ARISTOTLE trial demonstrated that apixaban had significantly lower rates of stroke/systemic embolism (SE) and major bleeding than warfarin; however, no direct clinical trials between apixaban and other direct oral anticoagulants (DOACs) are available. Few real-world studies comparing the effectiveness and safety between DOACs have been conducted. OBJECTIVE: To compare effectiveness, safety, and health care costs among oral anticoagulants (OACs) for nonvalvular atrial fibrillation (NVAF) patients in the U.S. Department of Defense (DoD) population. METHODS: Adult NVAF patients initiating warfarin or DOACs (apixaban, rivaroxaban, and dabigatran) were selected from U.S. DoD data from January 1, 2013, to September 30, 2015. The first OAC claim date was designated as the index date. Patients initiating another OAC were matched 1:1 to apixaban patients using propensity score matching to balance demographics and clinical characteristics. Cox proportional hazards models were used to estimate the risk of stroke/SE and major bleeding for each OAC versus apixaban. Generalized linear and two-part models with bootstrapping were used to compare all-cause health care costs and stroke/SE-related and major bleeding-related medical costs. RESULTS: Of the 41,001 eligible patients, 7,607 warfarin-apixaban, 4,129 dabigatran-apixaban, and 11,284 rivaroxaban-apixaban pairs were matched. Warfarin (HR = 1.84; 95% CI = 1.30-2.59; P < 0.001) and rivar-oxaban (HR = 1.46; 95% CI = 1.08-1.98; P = 0.015) were associated with a significantly higher risk of stroke/SE compared with apixaban. Dabigatran (HR = 1.17; 95% CI = 0.68-2.03; P = 0.573) was associated with a numerically higher risk of stroke/SE compared with apixaban. Warfarin (HR = 1.53; 95% CI = 1.24-1.89; P < 0.001), dabigatran (HR = 1.76; 95% CI = 1.27-2.43; P < 0.001), and rivaroxaban (HR = 1.59; 95% CI = 1.34-1.89; P < 0.001) were associated with higher risks of major bleeding compared with apixaban. Compared with apixaban, patients prescribed warfarin incurred numerically higher all-cause total health care costs per patient per month (PPPM) ($2,498 vs. $2,277; P = 0.148) and significantly higher stroke/SE-related ($118 vs. $46; P = 0.012) and major bleeding-related ($166 vs. $76; P = 0.003) medical costs. Dabigatran patients incurred numerically higher all-cause total health care PPPM costs ($2,372 vs. $2,143; P = 0.150) and stroke/SE-related medical costs ($61 vs. $32; P = 0.240) but significantly higher major bleeding-related costs ($114 vs. $58; P = 0.025). Rivaroxaban patients incurred significantly higher all-cause total health care costs ($2,546 vs. $2,200; P < 0.001) and major bleeding-related medical costs PPPM ($137 vs. $69; P < 0.001) but numerically higher stroke/SE-related medical costs PPPM ($58 vs. $38; P = 0.057). CONCLUSIONS: Among NVAF patients in the U.S. DoD population, warfarin and rivaroxaban were associated with a significantly higher risk of stroke/SE and major bleeding compared with apixaban. Dabigatran use was associated with a numerically higher risk of stroke/SE and a significantly higher risk of major bleeding compared with apixaban. Warfarin and dabigatran incurred numerically higher all-cause total health care costs compared with apixaban. Rivaroxaban was associated with significantly higher all-cause total health care costs compared with apixaban. DISCLOSURES This study was funded by Bristol-Myers Squibb and Pfizer, which were involved in the study design, as well as in the writing and revision of the manuscript. Keshishian and Zhang are paid employees of STATinMED Research, which was paid by Bristol-Myers Squibb and Pfizer to conduct this study and develop the manuscript. Gupta, Rosenblatt, Hede, and Nadkarni are paid employees of Bristol-Myers Squibb. Trocio, Dina, Mardekian, Liu, and Shank are paid employees of Pfizer.

A Real-World Observational Study of Hospitalization and Health Care Costs Among Nonvalvular Atrial Fibrillation Patients Prescribed Oral Anticoagulants in the U.S. Medicare Population.

BACKGROUND: Clinical trials have shown that direct oral anticoagulants (DOACs)-including dabigatran, rivaroxaban, apixaban, and edoxaban-are at least as effective and safe as warfarin for the risk of stroke/systemic embolism (SE) and major bleeding (MB) in patients with atrial fibrillation (AF). However, few studies have compared oral anticoagulants (OACs) among elderly patients. OBJECTIVE: To compare hospitalization risks (all-cause, stroke/SE-related, and MB-related) and associated health care costs among elderly nonvalvular AF (NVAF) patients in the Medicare population who initiated warfarin, dabigatran, rivaroxaban, or apixaban. METHODS: Patients (aged ≥ 65 years) initiating warfarin or DOACs (apixaban, rivaroxaban, and dabigatran) were selected from the Centers for Medicare & Medicaid Services database from January 1, 2013, to December 31, 2014. Patients initiating each OAC were matched 1:1 to apixaban patients using propensity score matching to balance demographic and clinical characteristics. Cox proportional hazards models were used to estimate the risk of hospitalization of each OAC versus apixaban. Generalized linear models and two-part models with bootstrapping were used to compare all-cause health care costs and stroke/SE- and MB-related medical costs between matched cohorts. RESULTS: Of the 186,132 eligible patients, 41,606 warfarin-apixaban, 30,836 dabigatran-apixaban, and 41,608 rivaroxaban-apixaban pairs were matched. The OACs were associated with a significantly higher risk of all-cause hospitalization compared with apixaban (warfarin: HR = 1.33, 95% CI = 1.27-1.38, P < 0.001; dabigatran: HR = 1.17, 95% CI = 1.11-1.23, P < 0.001; and rivaroxaban: HR = 1.27, 95% CI = 1.22-1.32, P < 0.001) and were associated with a significantly higher risk of hospitalization due to stroke/SE (warfarin: HR = 2.51, 95% CI = 1.92-3.29, P < 0.001; dabigatran: HR = 2.24, 95% CI = 1.60-3.13, P < 0.001; and rivaroxaban: HR = 1.74, 95% CI = 1.31-2.30, P < 0.001). Also, the OACs were associated with significantly higher risk of hospitalization due to MB-related conditions compared with apixaban (warfarin: HR = 1.96, 95% CI = 1.71-2.23, P < 0.001; dabigatran: HR = 1.48; 95% CI = 1.25-1.76, P < 0.001; and rivaroxaban: HR = 2.17, 95% CI = 1.91-2.48, P < 0.001). Compared with apixaban, warfarin ($3,747 vs. $3,061, P < 0.001); dabigatran ($3,230 vs. $2,951, P < 0.001); and rivaroxaban ($3,950 vs. $3,060, P < 0.001) had significantly higher all-cause total health care costs per patient per month. Patients initiating the OACs also had significantly higher stroke/SE- and MB-related medical costs compared with apixaban: warfarin (stroke/SE = $135 vs. $60, P = 0.001; MB = $537 vs. $286, P < 0.001); dabigatran (stroke/SE = $94 vs. $62, P = 0.045; MB = $373 vs. $277, P = 0.010); and rivaroxaban (stroke/SE = $91 vs. $60, P = 0.008; MB = $524 vs. $287, P < 0.001). CONCLUSIONS: This real-world study showed that among elderly NVAF patients in the Medicare population, apixaban was associated with significantly lower risks of all-cause, stroke/SE-related, and MB-related hospitalizations compared with warfarin, dabigatran, and rivaroxaban. Accordingly, apixaban showed significantly lower all-cause health care costs and stroke/SE- and MB-related medical costs. DISCLOSURES: This study was funded by Bristol-Myers Squibb and Pfizer. Amin is an employee of the University of California, Irvine, and was a paid consultant to Bristol-Myers Squibb in connection with this study and the development of this manuscript. Keshishian and Zhang are employees of STATinMED Research, a paid consultant to Pfizer and Bristol-Myers Squibb in connection with this study and the development of this manuscript. Trocio, Dina, Mardekian, and Liu are employees of Pfizer, with ownership of stocks in Pfizer. Le, Rosenblatt, Nadkarni, and Vo are employees of Bristol-Myers Squibb. Rosenblatt and Vo have ownership of stocks in Bristol-Myers Squibb. Baser has no conflicts to disclose.

Real-world comparison of all-cause hospitalizations, hospitalizations due to stroke and major bleeding, and costs for non-valvular atrial fibrillation patients prescribed oral anticoagulants in a US health plan.

AIMS: To compare the risk of all-cause hospitalization and hospitalizations due to stroke/systemic embolism (SE) and major bleeding, as well as associated healthcare costs for non-valvular atrial fibrillation (NVAF) patients initiating apixaban, dabigatran, rivaroxaban, or warfarin. MATERIALS AND METHODS: NVAF patients initiating apixaban, dabigatran, rivaroxaban, or warfarin were selected from the OptumInsight Research Database from January 1, 2013-September 30, 2015. Propensity score matching (PSM) was performed between apixaban and each oral anticoagulant. Cox models were used to estimate the risk of stroke/SE and major bleeding. Generalized linear and 2-part models were used to compare healthcare costs. RESULTS: Of the 47,634 eligible patients, 8,328 warfarin-apixaban pairs, 3,557 dabigatran-apixaban pairs, and 8,440 rivaroxaban-apixaban pairs were matched. Compared to apixaban, warfarin patients were associated with a significantly higher risk of all-cause (hazard ratio [HR] = 1.30; 95% confidence interval [CI] = 1.21-1.40) as well as stroke/SE-related (HR = 1.60; 95% CI = 1.23-2.07) and major bleeding-related (HR = 1.95; 95% CI = 1.60-2.39) hospitalization; rivaroxaban patients were associated with a higher risk of all-cause (HR = 1.15; 95% CI = 1.07-1.24) and major bleeding-related hospitalization (HR = 1.71; 95% CI = 1.39-2.10); and dabigatran patients were associated with a higher risk of major bleeding hospitalization (HR = 1.46, 95% CI = 1.02-2.10). Warfarin patients had significantly higher major bleeding-related and total all-cause healthcare costs compared to apixaban patients. Rivaroxaban patients had significantly higher major bleeding-related costs compared to apixaban patients. No significant results were found for the remaining comparisons. LIMITATIONS: No causal relationships can be concluded, and unobserved confounders may exist in this retrospective database analysis. CONCLUSIONS: This study demonstrated a significantly higher risk of hospitalization (all-cause, stroke/SE, and major bleeding) associated with warfarin, a significantly higher risk of major bleeding hospitalization associated with dabigatran or rivaroxaban, and a significantly higher risk of all-cause hospitalization associated with rivaroxaban compared to apixaban. Lower major bleeding-related costs were observed for apixaban patients compared to warfarin and rivaroxaban patients.

Risk of stroke/systemic embolism, major bleeding and associated costs in non-valvular atrial fibrillation patients who initiated apixaban, dabigatran or rivaroxaban compared with warfarin in the United States Medicare population.

OBJECTIVE: To compare the risk and cost of stroke/systemic embolism (SE) and major bleeding between each direct oral anticoagulant (DOAC) and warfarin among non-valvular atrial fibrillation (NVAF) patients. METHODS: Patients (≥65 years) initiating warfarin or DOACs (apixaban, rivaroxaban, and dabigatran) were selected from the Medicare database from 1 January 2013 to 31 December 2014. Patients initiating each DOAC were matched 1:1 to warfarin patients using propensity score matching to balance demographics and clinical characteristics. Cox proportional hazards models were used to estimate the risks of stroke/SE and major bleeding of each DOAC vs. warfarin. Two-part models were used to compare the stroke/SE- and major-bleeding-related medical costs between matched cohorts. RESULTS: Of the 186,132 eligible patients, 20,803 apixaban-warfarin pairs, 52,476 rivaroxaban-warfarin pairs, and 16,731 dabigatran-warfarin pairs were matched. Apixaban (hazard ratio [HR] = 0.40; 95% confidence interval [CI] 0.31, 0.53) and rivaroxaban (HR = 0.72; 95% CI 0.63, 0.83) were significantly associated with lower risk of stroke/SE compared to warfarin. Apixaban (HR = 0.51; 95% CI 0.44, 0.58) and dabigatran (HR = 0.79; 95% CI 0.69, 0.91) were significantly associated with lower risk of major bleeding; rivaroxaban (HR = 1.17; 95% CI 1.10, 1.26) was significantly associated with higher risk of major bleeding compared to warfarin. Compared to warfarin, apixaban ($63 vs. $131) and rivaroxaban ($93 vs. $139) had significantly lower stroke/SE-related medical costs; apixaban ($292 vs. $529) and dabigatran ($369 vs. $450) had significantly lower major bleeding-related medical costs. CONCLUSIONS: Among the DOACs in the study, only apixaban is associated with a significantly lower risk of stroke/SE and major bleeding and lower related medical costs compared to warfarin.