Costs associated with adverse events during treatment episodes for adult attention-deficit/hyperactivity disorder.

OBJECTIVE: Attention-deficit/hyperactivity disorder (ADHD) medication is frequently associated with adverse events (AEs), but limited real-world data exist regarding their costs from a payer's perspective. Therefore, this study evaluated the healthcare costs associated with common AEs among adult patients treated for ADHD in the US. METHODS: Eligible adults treated for ADHD were identified from a large US claims database (1 October 2015-30 September 2021). A retrospective cohort study design was used to assess excess healthcare costs and costs directly related to AE-specific claims per-patient-per-month (PPPM) associated with 10 selected AEs during ADHD treatment. To account for all costs associated with the AE, treatment episodes with a given AE were compared to similar treatment episodes without this AE. Entropy balancing was used to create cohorts with similar characteristics. Studied AEs were selected based on their prevalence in clinical trials for common ADHD medications and were identified from ICD-10-CM diagnosis codes recorded in claims. RESULTS: Among the 461,464 patients included (mean age: 34.2 years; 45.5% males), 49.4% had ≥1 AE during their treatment episode. Treatment episodes with AEs were associated with statistically significant AE-specific medical costs (erectile dysfunction: $57; fatigue: $82; dry mouth: $90; diarrhea: $162; insomnia: $147; anxiety: $281; nausea: $299; constipation: $356; urinary hesitation: $491; feeling jittery: $723) and excess healthcare costs PPPM (erectile dysfunction: $120, fatigue: $248, insomnia: $265, anxiety: $380, diarrhea: $441, dry mouth: $485, nausea: $709, constipation: $802, urinary hesitation: $1,105, feeling jittery: $1,160; p < .05). LIMITATIONS: AEs were identified based on recorded diagnosis on medical claims and likely represent more severe AEs. Therefore, costs may not be representative of milder AEs. CONCLUSIONS: This study found that AEs occurring during ADHD treatment episodes are associated with significant healthcare costs. This highlights the potential of treatments with favorable safety profiles to alleviate the burden experienced by patients and the healthcare system.

A real-world assessment of healthcare costs associated with agitation in Alzheimer's dementia.

AIMS: To describe and compare clinical characteristics, healthcare costs, and institutionalization/mortality outcomes among patients with and without agitation associated with Alzheimer's dementia (AAD). METHODS: Data from the Reliant Medical Group database (01/01/2016-03/31/2020) were used, including claims, electronic medical records, and clinical information/physician notes abstracted from medical charts. Patients aged ≥55 years with Alzheimer's dementia (AD) were observed during a randomly selected 12-month study period after AD diagnosis. Using information recorded in medical charts, patients were classified into cohorts based on experiencing (agitation cohort) and not experiencing (no agitation cohort) agitated behaviours during the study period. Entropy balancing was used to create reweighted cohorts with similar characteristics. Study outcomes (patient demographic and clinical characteristics, treatments received, healthcare costs, institutionalization and death events) were compared between cohorts; agitation characteristics were described for the agitation cohort only. RESULTS: Among 711 patients included in the study, 240 were classified in the agitation cohort and 471 in the no agitation cohort. After reweighting, several comorbidities were more frequently observed in the agitation versus no agitation cohort, including infection, depression, and altered mental status. Use of antidepressants, anticonvulsants, antipsychotics, and antianxiety medications was more common in the agitation versus no agitation cohort. Common agitated behaviours included hitting (20.8%), pacing/aimless wandering (17.5%), and cursing/verbal aggression (15.0%). Total all-cause healthcare costs were $4287 per-patient-per-year higher in the agitation cohort versus no agitation cohort (p = 0.04), driven by higher inpatient costs. Death was more common and time to death and institutionalization were shorter in the agitation versus no agitation cohort. LIMITATIONS: Results may not be generalizable to the US population with AD. CONCLUSIONS: Among patients with AD, agitation was associated with shorter time to death/institutionalization and increased comorbidities, medication use, and healthcare costs, highlighting the additional clinical and economic burden that agitation poses to patients and the healthcare system.

Treatment Patterns Among Patients with Attention-Deficit/Hyperactivity Disorder and Comorbid Anxiety and/or Depression in the United States: A Retrospective Claims Analysis.

INTRODUCTION: Patients with attention-deficit/hyperactivity disorder (ADHD) often have psychiatric comorbidities that may confound diagnosis and affect treatment outcomes and costs. The current study described treatment patterns and healthcare costs among patients with ADHD and comorbid anxiety and/or depression in the United States (USA). METHODS: Patients with ADHD initiating pharmacological treatments were identified from IBM MarketScan Data (2014-2018). The index date was the first observed ADHD treatment. Comorbidity profiles (anxiety and/or depression) were assessed during the 6-month baseline period. Treatment changes (discontinuation, switch, add-on, drop) were examined during the 12-month study period. Adjusted odds ratios (ORs) of experiencing a treatment change were estimated. Adjusted annual healthcare costs were compared between patients with and without treatment changes. RESULTS: Among 172,010 patients with ADHD (children [aged 6-12] N = 49,756; adolescents [aged 13-17] N = 29,093; adults [aged 18 +] N = 93,161), the proportion of patients with anxiety and depression increased from childhood to adulthood (anxiety 11.0%, 17.7%, 23.0%; depression 3.4%, 15.7%, 19.0%; anxiety and/or depression 12.9%, 25.4%, 32.2%). Compared with patients without the comorbidity profile, those with the comorbidity profile experienced a significantly higher odds of a treatment change (ORs [children, adolescents, adults] 1.37, 1.19, 1.19 for those with anxiety; 1.37, 1.30, 1.29 for those with depression; and 1.39, 1.25, 1.21 for those with anxiety and/or depression). Excess costs associated with a treatment change were generally higher with more treatment changes. Among patients with three or more treatment changes, annual excess costs per child, adolescent, and adult were $2234, $6557, and $3891 for those with anxiety; $4595, $3966, and $4997 for those with depression; and $2733, $5082, and $3483 for those with anxiety and/or depression. CONCLUSIONS: Over 12 months, patients with ADHD and comorbid anxiety and/or depression were significantly more likely to experience a treatment change than those without these psychiatric comorbidities and incurred higher excess costs with additional treatment changes.

Treatment patterns among children and adolescents with attention-deficit/hyperactivity disorder in the United States - a retrospective claims analysis.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a common neurobehavioral disorder affecting approximately 10.0% of children and 6.5% of adolescents in the United States (US). A comprehensive assessment of the current treatment landscape is warranted to highlight potential unmet needs of children and adolescents with ADHD. Therefore, this study described treatment patterns and healthcare costs among commercially insured children and adolescents with ADHD in the US. METHODS: Children and adolescents with ADHD initiating pharmacological treatment indicated for ADHD were identified from IBM MarketScan Commercial Database (2014-2018). A treatment sequence algorithm was used to examine treatment patterns, including discontinuation (≥ 180 days following the last day of supply of any ADHD treatment), switch, add-on, and drop (discontinuation of an agent in combination therapy), during the 12-month study period following the index date (i.e., first observed ADHD treatment). Total adjusted annual healthcare costs were compared between patients with and without treatment changes. RESULTS: Among 49,756 children and 29,093 adolescents included, mean age was 9 and 15 years, respectively, and 31% and 38% were female. As the first treatment regimen observed, 92% of both children and adolescents initiated a stimulant and 11% initiated combination therapy. Over half of the population had a treatment change over 12 months-59% of children and 68% of adolescents. Treatment discontinuation over 12 months was common in both populations-21% of children and 36% of adolescents discontinued treatment. Healthcare costs increased with the number of treatment changes observed; children and adolescents with treatment changes (i.e., 1, 2, or ≥ 3) incurred an incremental annual cost of up to $1,443 and $2,705, respectively, compared to those without a treatment change (p < 0.001). Costs were largely driven by outpatient visits. CONCLUSIONS: Over a 12-month period, treatment changes were commonly observed and were associated with excess costs, highlighting the unmet treatment needs of children and adolescents with ADHD in the US.

The Impact of Agitation in Dementia on Caregivers: A Real-World Survey.

BACKGROUND: Dementia patients frequently depend on caregivers. Agitation is a common behavioral dementia symptom particularly burdensome to patients and caregivers. OBJECTIVE: To assess the association of agitation severity with non-professional caregiver hours, burden, health status, and productivity. Secondarily, to assess the association of agitation severity with these outcomes for patients receiving remote (not living with the patient) and proximate (living with the patient) caregiving. METHODS: A retrospective analysis of physician and non-professional caregiver-reported data from a US point-in-time survey. Patients were aged ≥50 years, with early cognitive impairment or dementia. Regression analyses compared outcomes by agitation severity; covariates included age, sex, and clinical characteristics. RESULTS: Data were included for 1,349 patients (non-agitated n = 656, agitated n = 693; no care n = 305, remote care n = 248, proximate care n = 691; unknown care n = 105). Greater agitation was significantly associated (p < 0.05) in all caregivers with increasing: Zarit Burden Interview (ZBI) Total Caregiver Burden, Personal Strain, Role Strain, and Guilt; Work Productivity and Activity Index (WPAI) presenteeism, overall work impairment, and total activity impairment. Higher ZBI Total Caregiver Burden, Personal Strain, and Role Strain were associated with greater agitation in proximate caregivers and higher ZBI Guilt associated with greater agitation in remote caregivers (p < 0.05). Higher WPAI presenteeism and total activity impairment were associated (p < 0.05) with greater agitation in proximate caregivers. Caregiving hours increased with increasing agitation for proximate caregiving (p = 0.001). CONCLUSION: Greater agitation severity was associated with higher caregiver burden and lower productivity, with higher indirect costs a likely outcome of agitation.

The Economic Burden of Posttraumatic Stress Disorder in the United States From a Societal Perspective.

Objective: To estimate the economic burden of posttraumatic stress disorder (PTSD) in the United States civilian and military populations from a societal perspective.Methods: A prevalence-based and human capital approach was used to estimate the total excess costs of PTSD in 2018 from insurance claims data, academic literature, and governmental publications. Excess direct health care costs (pharmacy, medical), direct non-health care costs (research and training, substance use, psychotherapy, homelessness, disability), and indirect costs (unemployment, productivity loss, caregiving, premature mortality) associated with PTSD were compared between adults with PTSD and adults without PTSD, or the general population if information was not available for adults without PTSD.Results: The total excess economic burden of PTSD in the US was estimated at $232.2 billion for 2018 ($19,630 per individual with PTSD). Total excess costs were $189.5 billion (81.6%) in the civilian population and $42.7 billion (18.4%) in the military population, corresponding to $18,640 and $25,684 per individual with PTSD in the civilian and military populations, respectively. In the civilian population, the excess burden was driven by direct health care ($66.0 billion) and unemployment ($42.7 billion) costs. In the military population, the excess burden was driven by disability ($17.8 billion) and direct health care ($10.1 billion) costs.Conclusions: The economic burden of PTSD goes beyond direct health care costs and has been found to rival costs for other costly mental health conditions. Increased awareness of PTSD, development of more effective therapies, and expansion of evidence-based interventions may be warranted to reduce the large clinical and economic burden of PTSD.

Economic burden of attention-deficit/hyperactivity disorder among children and adolescents in the United States: a societal perspective.

OBJECTIVE: To provide a comprehensive evaluation of the economic burden associated with attention-deficit/hyperactivity disorder (ADHD) among children and adolescents from a US societal perspective. MATERIALS AND METHODS: Direct healthcare costs of children (5-11 years) and adolescents (12-17 years) with ADHD were obtained using claims data from the IBM MarketScan Research Databases (01/01/2017-12/31/2018). Direct non-healthcare and indirect costs were estimated based on literature and government publications. Each cost component was estimated using a prevalence-based approach, with per-patient costs extrapolated to the national level. RESULTS: The total annual societal excess costs associated with ADHD were estimated at $19.4 billion among children ($6,799 per child) and $13.8 billion among adolescents ($8,349 per adolescent). Education costs contributed to approximately half of the total excess costs in both populations ($11.6 billion [59.9%] in children; $6.7 billion [48.8%] in adolescents). Other major contributors to the overall burden were direct healthcare costs ($5.0 billion [25.9%] in children; $4.0 billion [29.0%] in adolescents) and caregiving costs ($2.7 billion [14.1%] in children; $1.6 billion [11.5%] in adolescents). LIMITATIONS: Cost estimates were calculated based on available literature and/or governmental publications due to the absence of a single data source for all costs associated with ADHD. Thus, the quality of cost estimates is limited by the accuracy of available data as well as the study populations and methodologies used by different studies. CONCLUSION: ADHD in children and adolescents is associated with a substantial economic burden that is largely driven by education costs, followed by direct healthcare costs and caregiver costs. Improved intervention strategies and policies may reduce the clinical and economic burden of ADHD in these populations.

Economic burden of attention-deficit/hyperactivity disorder among adults in the United States: a societal perspective.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is associated with substantial clinical burden as individuals transition to adulthood, including higher rates of comorbidities, mortality, incarceration, and psychiatric hospitalizations than in individuals without ADHD. These higher rates likely contribute to substantial economic burden as well. OBJECTIVE: To provide a comprehensive evaluation of the economic burden associated with ADHD in the US adult population. METHODS: Direct health care costs were obtained by using claims data from the IBM MarketScan Research Databases (January 1, 2017, through December 31, 2018). Direct non-health care costs and indirect costs were estimated on the basis of the literature and government publications. Excess costs incurred by adults with ADHD during 2018 were evaluated from a societal perspective; per-patient costs were extrapolated to the national level. RESULTS: An estimated 8.7 million adults live with ADHD in the United States, resulting in a total societal excess cost attributable to ADHD of $122.8 billion ($14,092 per adult). Excess costs of unemployment ($66.8 billion; 54.4%) comprised the largest proportion of the total, followed by productivity loss ($28.8 billion; 23.4%) and health care services ($14.3 billion; 11.6%). CONCLUSIONS: ADHD in adults is associated with substantial economic burden. DISCLOSURES: This study was funded by Otsuka Pharmaceutical Development & Commercialization, Inc. (Otsuka). The study sponsor contributed to and approved the study design, participated in the interpretation of data, and reviewed and approved the manuscript. Schein is an employee of Otsuka. Gagnon-Sanschagrin, Davidson, Kinkead, Cloutier, Guérin, and Lefebvre are employees of Analysis Group, Inc., a consulting company that provided paid consulting services to Otsuka to develop and conduct this study and write the manuscript. Adler has received research support from Shire/Takeda, Sunovion, and Otsuka; consulting fees from Bracket, Shire/Takeda, Sunovion, Otsuka, the State University of New York (SUNY), the National Football League (NFL), and Major League Baseball (MLB); and royalty payments (as inventor) from New York University (NYU) for license of adult ADHD scales and training materials. Childress has received research support from Allergan, Takeda/Shire, Emalex, Akili, Ironshore, Arbor, Aevi Genomic Medicine, Neos Therapeutics, Otsuka, Pfizer, Purdue, Rhodes, Sunovion, Tris, KemPharm, Supernus, and the US Food and Drug Administration; was on the advisory board of Takeda/Shire, Akili, Arbor, Cingulate, Ironshore, Neos Therapeutics, Otsuka, Pfizer, Purdue, Adlon, Rhodes, Sunovion, Tris, Supernus, and Corium; received consulting fees from Arbor, Ironshore, Neos Therapeutics, Purdue, Rhodes, Sunovion, Tris, KemPharm, Supernus, Corium, Jazz, and Tulex Pharma; received speaker fees from Takeda/Shire, Arbor, Ironshore, Neos Therapeutics, Pfizer, Tris, and Supernus; and received writing support from Takeda/Shire, Arbor, Ironshore, Neos Therapeutics, Pfizer, Purdue, Rhodes, Sunovion, and Tris. Part of the material in this study was presented as a poster at the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) 2021 Virtual Meeting; May 17-20, 2021.

Treatment patterns among adults with attention-deficit/hyperactivity disorder in the United States: a retrospective claims study.

OBJECTIVE: To assess treatment patterns in adults with attention-deficit/hyperactivity disorder (ADHD) and associated healthcare costs in a real-world US setting. METHODS: Claims data from the IBM MarketScan Commercial Subset (Q1/2014-Q4/2018) was used to identify adults diagnosed with ADHD who newly initiated on ADHD treatment (index date). Treatment sequences were defined using an algorithm; for each sequence, the regimen comprised all ADHD-related agents observed within 30 d of the first agent during the 12-month study period. Treatment changes included discontinuation, switch, add-on, and drop. Treatment characteristics were described for the first treatment regimen observed. Total adjusted annual healthcare costs were compared between patients with no treatment change and patients with 1, 2, and ≥3 treatment changes. RESULTS: Among 122,881 adults with ADHD, the majority initiated a stimulant (95.1%) as their first treatment regimen observed; 9.3% of patients initiated combination therapy of ≥2 ADHD-related agents, and 34.9% of patients had psychotherapy. After an average first treatment regimen duration of 7.1 months, 50.2% of patients experienced a treatment change (22.5% discontinued, 17.5% switched, 5.3% had an add-on, and 4.6% had a treatment drop). Among those who discontinued, 44.8% did so within the first month of initiation. Mean annual healthcare costs were higher among patients with at least 1 treatment change compared to those with no treatment changes; excess costs increased with each additional treatment change. CONCLUSIONS: Treatment changes were commonly observed and were associated with excess healthcare cost, emphasizing the unmet treatment needs of adults with ADHD in the US.

Direct Costs of Opioid Abuse in an Insured Population in the United States.

OBJECTIVE: To (a) describe the demographics of opioid abusers; (b) compare the prevalence rates of selected comorbidities and the medical and drug utilization patterns of opioid abusers with patients from a control group, for the period from 1998 to 2002; and (c) calculate the mean annual per-patient total health care costs (e.g., inpatient, outpatient, emergency room, drug, other) from the perspective of a private payer. METHODS: An administrative database of medical and pharmacy claims from 1998 to 2002 of 16 self-insured employer health plans with approximately 2 million lives was used to identify "opioid abusers"-patients with claims associated with ICD-9-CM (International Classification of Diseases, 9th Revision, Clinical Modification) codes for opioid abuse (304.0, 304.7, 305.5, and 965.0 [excluding 965.01]). A control group of nonabusers was selected using a matched sample (by age, gender, employment status, and census region) in a 3:1 ratio. Per-patient annual health care costs (mean total medical and drug costs) were measured in 2003 U.S. dollars. Multivariate regression techniques were also used to control for comorbidities and to compare costs with a benchmark of depressed patients. RESULTS: 740 patients were identified as opioid abusers, a prevalence of 8 in 10,000 persons aged 12 to 64 years continuously enrolled in health care plans for whom 12 months of data were available for calculating costs. Opioid abusers, compared with nonabusers, had significantly higher prevalence rates for a number of specific comorbidities, including nonopioid poisoning, hepatitis (A, B, or C), psychiatric illnesses, and pancreatitis, which were approximately 78, 36, 9, and 21 (P<0.01) times higher, respectively, compared with nonabusers. Opioid abusers also had higher levels of medical and prescription drug utilization. Almost 60% of opioid abusers had prescription drug claims for opioids compared with approximately 20% for nonabusers. Prevalence rates for hospital inpatient visits for opioid abusers were more than 12 times higher compared with nonabusers (P<0.01). Mean annual direct health care costs for opioid abusers were more than 8 times higher than for nonabusers ($15,884 versus $1,830, respectively, P < 0.01). Hospital inpatient and physician-outpatient costs accounted for 46% ($7,239) and 31% ($5,000) of opioid abusers' health care costs, compared with 17% ($310) and 50% ($906), respectively, for nonabusers. Mean drug costs for opioid abusers were more than 5 times higher than costs for nonabusers ($2,034 vs. $386, respectively, P<0.01), driven by higher drug utilization (including opioids) for opioid abusers. Even when controlling for comorbidities using a multivariate regression model of a matched control of depressed patients, the average health care costs of opioid abusers were 1.8 times higher than the average health care costs of depressed patients. CONCLUSION: The high costs of opioid abuse were driven primarily by high prevalence rates of costly comorbidites and high utilization rates of medical services and prescription drugs. DISCLOSURES: Funding for this research was provided by an unrestricted grant from Janssen Medical Affairs, L.L.C. and was obtained by authors Susan Vallow and Jeff Schein, who are employed by Janssen Medical Affairs, L.L.C. Nathaniel Katz is a consultant to Janssen and numerous other pharmaceutical companies that manufacture branded opioid products and nonopioid analgesics; authors Alan G. White, Howard G. Birnbaum, Milena N. Mareva, and Maham Daher disclose no potential bias or conflict of interest relating to this article. White served as principal author of the study. Study concept and design were contributed primarily by White, Vallow, Schein, and Katz. Analysis and interpretation of data were contributed by all authors. Drafting of the manuscript was primarily the work of White, and its critical revision was the work of White and Vallow. Statistical expertise was contributed by White, Birnbaum, and Daher, and administrative, technical, and/or material support was provided by Analysis Group, Inc., Boston, MA.

Healthcare resource utilization and costs associated with venous thromboembolism in cancer patients treated with anticoagulants.

Objective: The standard of care for cancer-related venous thromboembolism (VTE) has been low molecular weight heparin (LMWH), but oral anticoagulants are also widely prescribed. This study compared VTE-related healthcare resource utilization and costs of cancer patients treated with anticoagulants. Methods: Claims data from Humana Database (January 1, 2013-May 31, 2015) were analyzed. Based on the first anticoagulant received, patients were classified into LMWH, warfarin, or rivaroxaban cohorts. Characteristics were evaluated during the 6 months pre-index date (i.e. the first VTE); VTE-related resource utilization and costs were evaluated during follow-up. Cohorts were compared using rate ratios, and p-values and 95% confidence intervals were calculated. Healthcare costs were evaluated per-patient-per-year (PPPY) and compared using mean cost differences. Results: A total of 2,428 patients (LMWH: n = 660; warfarin: n = 1,061; rivaroxaban: n = 707) were included. Compared to patients treated with LMWH, patients treated with rivaroxaban had significantly fewer VTE-related hospitalizations, hospitalization days, and emergency room and outpatient visits, resulting in an increase of $12,000 VTE-related healthcare costs PPPY with LMWH vs rivaroxaban. Patients treated with rivaroxaban had significantly lower VTE-related resource utilization compared to patients treated with warfarin; however, VTE-related costs were similar between cohorts. The higher drug costs ($1,519) were offset by significantly lower outpatient (-$1,039) and hospitalization costs (-$522) in rivaroxaban relative to the warfarin cohort. Conclusions: Healthcare resource use and costs associated with VTE treatment in cancer patients are highest with LMWH relative to warfarin and rivaroxaban.

Healthcare costs of stroke and major bleeding in patients with atrial fibrillation treated with non-vitamin K antagonist oral anticoagulants.

Objective: To assess long-term healthcare costs related to ischemic stroke and systemic embolism (stroke/SE) and major bleeding (MB) events in patients with non-valvular atrial fibrillation (NVAF) treated with non-vitamin K antagonist oral anticoagulants (NOACs). Materials and methods: Optum's Clinformatics Data Mart database from 1/2009-12/2016 was analyzed. Adult patients with ≥1 stroke/SE hospitalization (index date) were matched 1:1 to patients without stroke/SE (random index date), based on propensity scores. Patients with an MB event were matched to patients without MB. All patients had an NOAC dispensing overlapping index date, ≥12 months of eligibility pre-index date, and ≥1 NVAF diagnosis. The observation period spanned from the index date until the earliest date of death, switch to warfarin, end of insurance coverage, or end of data availability. Mean costs were evaluated: (1) per-patient-per-year (PPPY) and (2) at 1, 2, 3, and 4 years using Lin's method. Results: The cost differences were, respectively, $48,807 and $28,298 PPPY for NOAC users with stroke/SE (n = 1,340) and those with MB (n = 3,774) events compared to controls. Cost differences of patients with vs without stroke/SE were $49,876, $51,627, $57,822, and $60,691 at 1, 2, 3, and 4 years post-index, respectively (p < 0.001). These cost differences were $31,292, $35,658, $44,069, and $47,022 for patients with vs without MB after 1, 2, 3, and 4 years post-index, respectively (p < 0.001). Limitations: Limitations include unobserved confounders, coding and/or billing inaccuracies, limited sample sizes over longer follow-up, and the under-reporting of mortality for deaths occurring after 2011. Conclusions: The incremental healthcare costs incurred by patients with vs without stroke/SE was nearly twice as high as those of patients with vs without MB. Moreover, each additional year up to 4 years after the first event was associated with an incremental cost for patients with a stroke/SE or MB event compared to those without an event.

The value of sPESI for risk stratification in patients with pulmonary embolism.

INTRODUCTION: Various risk stratification methods exist for patients with pulmonary embolism (PE). We used the simplified Pulmonary Embolism Severity Index (sPESI) as a risk-stratification method to understand the Veterans Health Administration (VHA) PE population. MATERIALS AND METHODS: Adult patients with ≥ 1 inpatient PE diagnosis (index date = discharge date) from October 2011-June 2015 as well as continuous enrollment for ≥ 12 months pre- and 3 months post-index date were included. We defined a sPESI score of 0 as low-risk (LRPE) and all others as high-risk (HRPE). Hospital-acquired complications (HACs) during the index hospitalization, 90-day follow-up PE-related outcomes, and health care utilization and costs were compared between HRPE and LRPE patients. RESULTS: Of 6746 PE patients, 95.4% were men, 67.7% were white, and 22.0% were African American; LRPE occurred in 28.4% and HRPE in 71.6%. Relative to HRPE patients, LRPE patients had lower Charlson Comorbidity Index scores (1.0 vs. 3.4, p < 0.0001) and other baseline comorbidities, fewer HACs (11.4% vs. 20.0%, p < 0.0001), less bacterial pneumonia (10.6% vs. 22.3%, p < 0.0001), and shorter average inpatient lengths of stay (8.8 vs. 11.2 days, p < 0.0001) during the index hospitalization. During follow-up, LRPE patients had fewer PE-related outcomes of recurrent venous thromboembolism (4.4% vs. 6.0%, p = 0.0077), major bleeding (1.2% vs. 1.9%, p = 0.0382), and death (3.7% vs. 16.2%, p < 0.0001). LRPE patients had fewer inpatient but higher outpatient visits per patient, and lower total health care costs ($12,021 vs. $16,911, p < 0.0001) than HRPE patients. CONCLUSIONS: Using the sPESI score identifies a PE cohort with a lower clinical and economic burden.

Cardiovascular outcomes among elderly patients with heart failure and coronary artery disease and without atrial fibrillation: a retrospective cohort study.

BACKGROUND: Coronary artery disease accelerates heart failure progression, leading to poor prognosis and a substantial increase in morbidity and mortality. This study was aimed to assess the impact of coronary artery disease on all-cause mortality, myocardial infarction (MI), and ischemic stroke (IS) among hospitalized newly-diagnosed heart failure (HF) patients with left ventricular systolic dysfunction (LVSD). METHODS: This retrospective cohort study included Medicare patients (aged ≥65 years) with ≥1 inpatient heart failure claim (index date = discharge date) during 01JAN2007-31DEC2013. Patients were required to have continuous enrollment for ≥1-year pre-index date (baseline: 1-year pre-index period) without a prior heart failure claim (in the 1 year pre-index prior to the index hospital admission); follow-up ran from the index date to death, disenrollment from the health plan, or the end of the study period, whichever occurred first. HF with LVSD patients, identified with diagnosis codes of systolic dysfunction (excluding baseline atrial fibrillation), were stratified based on prevalent coronary artery disease at baseline into coronary artery disease and non-coronary artery disease cohorts. Main outcomes were occurrence of major adverse cardiovascular events including all-cause mortality, myocardial infarction, and ischemic stroke. Propensity score matching (PSM) was used to balance patient characteristics. Kaplan-Meier curves of ACM and cumulative incidence distribution of MI/IS were presented. RESULTS: Of 22,230 HF with LVSD patients, 15,827 (71.2%) had coronary artery disease and were overall more likely to be younger (79.8 vs 80.9 years), male (49.6% vs. 35.6%), white (86.2% vs 81.4%), with more prevalent comorbidities including hypertension (80.7% vs 74.3%), hyperlipidemia (67.7% vs 46.7%), and diabetes (46.3% vs 35.8%) (all p < 0.0001). After propensity score matching, cohorts included 5792 patients each. The coronary artery disease cohort had significantly higher cumulative incidence of myocardial infarction and ischemic stroke at the end of 7-year follow-up vs non-coronary artery disease (myocardial infarction = 50.0% vs 18.0%; ischemic stroke = 23.3% vs 18.7%; all p < 0.0001). Follow-up all-cause mortality rates were similar between the two cohorts. CONCLUSIONS: HF with LVSD patients with coronary artery disease had significantly higher incidence of ischemic stroke and myocardial infarction, but similar all-cause mortality compared to those without coronary artery disease.

Comparison of real-world outcomes in patients with nonvalvular atrial fibrillation treated with direct oral anticoagulant agents or warfarin.

PURPOSE: To compare patients with atrial fibrillation (AF) initiating direct oral anticoagulants (DOACs) versus warfarin on clinical outcomes including stroke, systemic embolism (SE), bleeding events, and cost of care. METHODS: This retrospective observational study used Medicare Advantage Prescription Drug and fully insured commercial claims from the Humana Research Database. Patients with AF who initiated a DOAC or warfarin from January 1, 2012, through September 30, 2015, were included. Date of the first prescription of DOAC or warfarin was the index date. Patients in the DOAC and warfarin groups were matched on propensity scores. Patients were censored at end of enrollment or study period, discontinuation, or switch of index medication. Clinical outcomes were compared in the matched groups using Cox proportional hazards models. Annualized costs and costs adjusted for censoring using Lin's interval method were also compared between the two cohorts. RESULTS: Patients on DOACs had a significantly lower risk of ischemic stroke (hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.79-0.98), hemorrhagic stroke (HR, 0.65; CI, 0.46-0.92), SE (HR, 0.53; 95% CI, 0.43-0.65), and composite outcome of stroke or SE (HR, 0.78; 95% CI, 0.71-0.86) compared with patients on warfarin. Bleeding risk was not statistically significant (HR, 0.85; 95% CI, 0.71-1.01). While annualized pharmacy costs were higher, annualized medical and total costs were lower in the DOAC group compared with the warfarin group. CONCLUSION: The results of the study indicated that patients on DOACs had lower rates of ischemic stroke, hemorrhagic stroke, SE, and composite outcome of stroke or SE compared with patients on warfarin. No significant differences in bleeding rates between the DOAC and warfarin groups were observed, while total cost of care was lower in the DOAC group.

Clinical and Economic Outcomes in Low-risk Pulmonary Embolism Patients Treated with Rivaroxaban versus Standard of Care.

BACKGROUND: Rivaroxaban, a fixed-dose oral direct factor Xa inhibitor, does not require continuous monitoring and thus reduces the hospital stay and economic burden in low-risk pulmonary embolism (LRPE) patients. Study Question: What is the effectiveness of rivaroxaban versus the standard of care (SOC; low-molecular-weight heparin, unfractionated heparin, warfarin) among LRPE patients in the Veterans Health Administration? STUDY DESIGN: Adult patients with continuous health plan enrollment for ≥12 months pre- and 3 months post-inpatient PE diagnosis (index date=discharge date) between October 1, 2011-June 30, 2015 and an anticoagulant claim during the index hospitalization were included. MEASURES AND OUTCOMES: Patients scoring 0 points on the simplified Pulmonary Embolism Stratification Index were considered low-risk and were stratified into SOC and rivaroxaban cohorts. Propensity score matching (PSM) was used to compare hospital-acquired complications (HACs), PE-related outcomes (recurrent venous thromboembolism, major bleeding, and death), and healthcare utilization and costs between the rivaroxaban and SOC cohorts. RESULTS: Among 6746 PE patients, 1918 were low-risk; of these, 73 were prescribed rivaroxaban, 1546 were prescribed SOC, and 299 were prescribed other anticoagulants during the index hospitalization. After 1:3 PSM, 64 rivaroxaban and 192 SOC patients were included. During the index hospitalization, rivaroxaban users (versus SOC) had similar inpatient length of stay (LOS; 7.0 vs 6.7 days, standardized difference [STD]=1.8) but fewer HACs (4.7% vs 10.4%; STD: 21.7). In the 90-day post-discharge period, PE-related outcome rates were similar between the cohorts (all p>0.05). However, rivaroxaban users had fewer outpatient (15.9 vs 20.4; p=0.0002) visits per patient as well as lower inpatient ($765 vs $2,655; p<0.0001), pharmacy ($711 vs $1,086; p=0.0033), and total costs ($6,270 vs $9,671; p=0.0027). CONCLUSIONS: LRPE patients prescribed rivaroxaban had similar index LOS and PE-related outcomes, but fewer HACs, and lower total costs than those prescribed SOC.

Health-care Cost Impact of Continued Anticoagulation With Rivaroxaban vs Aspirin for Prevention of Recurrent Symptomatic VTE in the EINSTEIN-CHOICE Trial Population.

BACKGROUND: Using data from the Reduced-Dose Rivaroxaban in the Long-Term Prevention of Recurrent Symptomatic Venous Thromboembolism (EINSTEIN-CHOICE) trial, this study assessed cost impact of continued anticoagulation therapy with rivaroxaban vs aspirin. METHODS: Total health-care costs (2016 USD) associated with rivaroxaban and aspirin were calculated as the sum of clinical event costs and drug costs from a US managed care perspective. Clinical event costs were calculated by multiplying event rate by cost of care. One-year Kaplan-Meier clinical event rates for recurrent pulmonary embolism, recurrent DVT, all-cause mortality, and bleeding were obtained from EINSTEIN-CHOICE. Cost of care was determined by literature review. Drug costs were the product of drug price (wholesale acquisition cost) and treatment duration. A one-way sensitivity analysis was conducted. RESULTS: Rivaroxaban users had lower per patient per month (PPPM) clinical event costs compared with aspirin users ($123, $243, and $381 for rivaroxaban 10 mg, rivaroxaban 20 mg, and aspirin, respectively). However, vs aspirin, PPPM total health-care costs were $24 higher for patients treated with rivaroxaban 10 mg ($143 higher for rivaroxaban 20 mg) due to higher cost of rivaroxaban. With a 15% discount for rivaroxaban 10 mg, the lower cost of clinical events for the rivaroxaban-treated patients more than fully offset the higher drug costs, and yielded a $19 lower total health-care cost. CONCLUSIONS: Continued therapy with rivaroxaban 10 and 20 mg vs aspirin was associated with lower clinical event costs but higher total health-care costs; with a 15% drug discount rivaroxaban 10 mg had lower total health-care costs than aspirin.

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.

Cost comparison of continued anticoagulation with rivaroxaban versus placebo based on the 1-year EINSTEIN-Extension trial efficacy and safety results.

AIMS: The EINSTEIN-Extension trial (EINSTEIN-EXT) found that continued treatment with rivaroxaban for an additional 6 or 12 months (vs placebo) after 6-12 months of initial anticoagulation significantly reduced the risk of recurrent venous thromboembolism (VTE) with a small non-significant increased risk of major bleeding (none fatal or in critical site). This study aimed to compare total healthcare cost between rivaroxaban and placebo, based on the EINSTEIN-EXT event rates. METHODS: Total healthcare cost was calculated as the sum of treatment and clinical event costs from a US managed care perspective. Treatment duration and event rates were obtained from the EINSTEIN-EXT study. Adjustment on treatment duration was made by assuming a 10% non-adherence rate. Drug costs were based on wholesale acquisition costs. Cost estimates for clinical events (i.e. recurrent deep vein thrombosis [DVT], recurrent pulmonary embolism, major bleeding, clinically relevant non-major bleeding) were determined from the literature. Results were examined over a ±20% range of each cost component and over 95% confidence intervals (CIs) of event rate differences in deterministic (one-way) and probabilistic sensitivity analyses (PSA). RESULTS: Total healthcare cost was $1,454 lower for rivaroxaban-treated (vs placebo-treated) patients in the base-case, with a lower clinical event cost fully offsetting drug cost. The cost savings of recurrent DVT alone (-$3,102) was greater than drug cost ($2,723). Total healthcare cost remained lower for rivaroxaban in the majority (73%) of PSA (cost difference [95% CI] = -$1,454 [-$2,396, $1,231]). LIMITATIONS: This study was conducted over the 1-year observation period of the EINSTEIN-EXT trial, which limited "real-world" applicability and examination of long-term economic impact. Assumptions on drug and clinical event costs were US-based and, thus, not applicable to other healthcare systems. CONCLUSIONS: Total healthcare costs were estimated to be lower for patients continuing rivaroxaban therapy compared to those receiving placebo in VTE patients who had completed 6-12 months of VTE treatment.