Effect of Ferric Carboxymaltose Versus Low-Dose Intravenous Iron Therapy and Iron Sucrose on the Total Cost of Care in Patients with Iron Deficiency Anemia: A US Claims Database Analysis.

BACKGROUND AND OBJECTIVE: Iron deficiency is the most common cause of anemia. We compared the effect of ferric carboxymaltose (FCM), low-dose intravenous (IV) iron (LDI), and iron sucrose on total cost of care in patients with iron-deficiency anemia (IDA) from a US health plan perspective. METHODS: We conducted a retrospective claims analysis using the IQVIA PharMetrics Plus database. Patients with index (first) claims of FCM and LDI and a medical claim associated with IDA between 1 January 2017 and 31 December 2019 were included. Monthly total healthcare and inpatient and outpatient costs after receiving index IV iron for patients in the treatment cohorts were compared using a generalized linear model with gamma distribution and log-link. RESULTS: The overall study cohort included 37,655 FCM, 44,237 LDI, and 27,461 iron sucrose patients. Mean per-patient-per-month numbers of IV iron infusions for FCM, LDI, and iron sucrose were 0.20, 0.34, and 0.37, respectively. Compared with baseline, the FCM group had greater reductions in the number of hospital admissions and smaller increases in the number of outpatient visits in the 12 months post-IV iron therapy than LDI and iron sucrose, translating to significantly lower total healthcare cost (post-index adjusted cost ratio for total cost: 0.96 and 0.92, respectively; both P < 0.0001). CONCLUSIONS: Higher drug acquisition cost of FCM relative to LDI and iron sucrose was offset by significantly lower inpatient and outpatient costs in the 12 months post-IV iron therapy. These results support the economic value of FCM for patients with IDA receiving IV iron therapy.

Iron deficiency is one of the most common causes of anemia. Patients with iron deficiency anemia (IDA) may require IV iron replacement therapy. This study was a retrospective claims analysis that utilized medical and pharmacy claims from the IQVIA PharMetrics Plus database. We found that ferric carboxymaltose (FCM), a high-dose formulation of IV iron that delivers up to 1500 mg per course of treatment, was associated with lower inpatient and outpatient costs than low-dose IV iron formulations (LDI) in the 12 months following treatment, offsetting its higher drug acquisition cost relative to LDI. Analysis of subgroups with chronic conditions (cancer, chronic kidney disease, and heart failure) showed greater levels of cost reductions with use of FCM than in the overall study cohort. Findings from this real-world analysis are consistent with previous studies, indicating that FCM was a cost-effective treatment option for IDA.

Treatment Patterns and Adverse Event-Related Hospitalization Among Patients with Epidermal Growth Factor Receptor (EGFR)-Mutated Metastatic Non-small Cell Lung Cancer After Treatment with EGFR Tyrosine Kinase Inhibitor and Platinum-Based Chemotherapy Regimens.

BACKGROUND: Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR TKIs) are established first-line treatments among patients with metastatic non-small cell lung cancer harboring EGFR-sensitizing mutations. Upon EGFR TKI resistance, there are scant data supporting a standard of care in subsequent lines of therapy. OBJECTIVE: We aimed to characterize real-world treatment patterns and adverse events associated with hospitalization in later lines of therapy. METHODS: This retrospective analysis of administrative claims included adults with metastatic non-small cell lung cancer who initiated a next line of therapy (index line of therapy) following EGFR TKI and platinum-based chemotherapy discontinuation on/after 1 November, 2015. Treatment regimens and adverse event rates during the index line of therapy were described. RESULTS: Among 195 eligible patients (median age: 59 years; female: 60%), the five most common index line of therapy regimens were immune checkpoint inhibitor monotherapy (29%), EGFR TKI monotherapy (21%), platinum-based chemotherapy (19%), non-platinum-chemotherapy (13%), and EGFR TKI combinations (9%). The overall median (95% confidence interval) time to discontinuation of the index line of therapy was 2.8 (2.1-3.2) months. Common adverse events associated with hospitalizations included infection/sepsis, pneumonia/pneumonitis, and anemia (2.9, 2.8, and 2.0 per 100 person-months, respectively). CONCLUSIONS: Among EGFR TKI-resistant patients who discontinued platinum-based chemotherapy, the duration of the next line of therapy was short, treatment was highly variable, and re-treatment with EGFR TKIs and platinum-based regimens was common, suggesting a lack of standard of care in later lines. Adverse event rates associated with hospitalization were high, especially among platinum-treated patients. These results underscore the unmet need for new therapies in a later line of treatment to reduce the clinical burden among patients in this population.

Relationship Between Initial Parenteral Iron Therapy Dosing and Treatment Effectiveness: A Real-World Retrospective Analysis.

Purpose: Replacement iron is the main treatment for iron deficiency, but the relationship between initial intravenous (IV) dose and need for additional treatment is unclear. This study explored patterns of IV iron dosing in US clinical practice. Methods: Patient records were obtained for adults who received IV iron for anemia between 2015 and 2017. Patients were classified into four groups: those who received <1500 mg and ≥1500 mg IV iron and those received ≤1000 mg and >1000 mg within 3 weeks of their first dose. The proportion of patients requiring additional IV iron after 30 days of the initial dose was evaluated. Results: Data were obtained for 2959 patients receiving iron sucrose (44.2%), ferric carboxymaltose injection (FCM) (25.8%), and ferumoxytol (FM) (14.3%). Overall, 567 patients (19%) received ≥1500 mg of IV iron and 942 (32%) received >1000 mg of IV iron within the first 21 days. Mean (SD) baseline iron deficit was 1001 mg (312). Patients who received ≥1500 mg had a 32% lower probability of receiving additional IV iron than those who received <1500 mg (adjusted hazard ratio [HR]: 0.68 [95% confidence interval (CI); 0.58, 0.81]) and incurred significantly fewer outpatient visits for all causes (p < 0.001) and IV iron treatment (p < 0.001). Patients who received an initial dose of >1000 mg had a 41% lower probability of receiving additional IV iron than those who received ≤1000 mg (adjusted HR: 0.59 [95% CI; 0.52, 0.67]) and had significantly fewer outpatient visits for all causes (p < 0.001) and IV iron treatment (p < 0.001). Patients receiving FCM required fewer outpatient visits than those receiving FM and other treatments, including a subgroup of patients who initially received >1000 mg IV iron. Conclusion: Higher doses of IV iron within 3 weeks of first dose may reduce further IV iron treatment needs and outpatient visits.

Factors associated with time to EGFR TKI treatment in patients with non-squamous metastatic non-small-cell lung cancer.

Aim: Assess factors associated with EGFR TKI initiation among patients with metastatic non-small-cell lung cancer (mNSCLC). Patients & methods: Medicare Part D patients diagnosed with non-squamous mNSCLC and starting an EGFR TKI within 1 year of diagnosis were selected from the Surveillance, Epidemiology and End Results (SEER)-Medicare database. Associations between patient characteristics and time from diagnosis to treatment initiation (time-to-treatment [TTT]) were analyzed. Results: Among the sample (n = 890), the patients who were younger, African-American or from rural communities had significantly longer TTT. Patients who did not receive surgery, who were Asian and those with brain metastases had significantly shorter TTT. Conclusion: Patient demographics and clinical characteristics may affect timeliness of EGFR TKI treatment for mNSCLC. Future research should examine potential barriers to treatment.

This study aimed to identify factors that may affect the time to initiate treatment with a product in the EGFR TKI class of drugs for patients with metastatic non-small-cell lung cancer (mNSCLC). We used an anonymized database that combines health information on cancer patients (SEER) with insurance claims information for Medicare Part D patients. Our study included 890 patients. We found that patients who were younger, African­American or from rural communities had longer times to starting treatment. Patients who did not receive surgery, who were Asian and those with cancer that had spread to the brain had notably shorter times to starting treatment. Further research should examine potential barriers that may contribute to treatment initiation delay.

Safe Opioid Storage and Disposal: A Survey of Patient Beliefs and Practices.

OBJECTIVE: To evaluate knowledge, practices, and beliefs of US patients receiving prescription opioids regarding opioid storage, disposal, and diversion. DESIGN: Internet-based, cross-sectional survey conducted between September and October 2018. Fisher's exact tests and Kendall's Tau-c were used to assess associations with storage and disposal outcomes. PARTICIPANTS: Patients aged ≥18 years with acute (n=250) or chronic noncancer (n=250) pain were prescribed an oral opioid within 90 days of the survey. RESULTS: Mean (SD) patient age was 48 (14.7) years, 57.2% were female, 82.6% lived with ≥1 person in the home, and 28.0% had remaining/unused pills. One-third of all patients received safe opioid storage (35.2%) and/or disposal (31.4%) counseling from a healthcare provider, while 50.0% received neither storage nor disposal information. Only 27.4% of all patients stored their opioids in a locked location, and 17.9% of those with remaining/unused pills disposed of their medication. Patients who received any opioid counseling were more likely to keep their medication in a locked location compared with those who did not (42.4% vs 12.4%, respectively; P<0.0001), as were those who perceived any risk of opioid diversion in the home compared with those who perceived no risk or were unsure (53.7% vs 24.2%, respectively; P<0.0001). Disposal rates did not differ based on counseling received (20.8% counseled vs 16.1% not counseled; P=0.5011) or perceived diversion risk (27.8% perceived any risk vs 16.4% perceived no risk or unsure; P=0.3166). CONCLUSION: The proportion of patients receiving prescription opioids who receive safe storage/disposal counseling from a healthcare provider appears suboptimal. Further research is warranted to develop effective ways to improve patient opioid storage/disposal education and practices.

Assessment of Work Loss Associated With Prescription-Related Opioid Use Disorder: A Retrospective Analysis of Claims Data.

OBJECTIVE: Quantify work loss and costs associated with prescription opioid use disorder (OUD) from the employer perspective. METHODS: Retrospective claims analysis to compare missed work days and associated costs between employees with and without an OUD diagnosis in a 12-month period. RESULTS: Two thousand three hundred eleven matched-pairs of employees were compared. The mean (SD) number of days missed while waiting for disability benefits (0.24 [1.4] vs 0.17 [1.0]; P = 0.035), absenteeism due to disability claims (9.5 [40.9] vs 5.6 [30.0]; P < 0.001), and medical visits (17.8 [18.5] vs 10.0 [12.4]; P < 0.001) was higher for employees with OUD compared with those without, resulting in higher mean (SD) indirect cost estimates of $8193 ($14,694) per employee (OUD) versus $5438 ($13,683) per employee (no OUD) (P < 0.001). CONCLUSIONS: Prescription OUD is associated with significant work loss and may pose considerable economic burden on employers.

Association Between Formulary Coverage and Use of Abuse-Deterrent Prescription Opioids, Risk for Abuse or Overdose, and Associated Healthcare Resource Utilization.

BACKGROUND: Significant public health concerns exist regarding the misuse and abuse of prescription opioids. Abuse-deterrent formulation (ADF) opioids may be leveraged as an important tool for combating the current opioid crisis. OBJECTIVES: To evaluate the relationships between ADF opioid formulary coverage and the ADF utilization rate, the risk for opioid abuse or overdose, opioid abuse or overdose-related healthcare resource utilization, and medical costs within a calendar year. METHODS: This cross-sectional multiyear panel study included adults prescribed an opioid medication in 2015 or 2016. We analyzed the medical and pharmacy claims linked to health plan benefit design data. An ADF opioid-including reformulated oxycodone hydrochloride (HCl) controlled-release (CR; reformulated OxyContin), morphine sulfate and naltrexone HCl extended-release (ER; Embeda), and hydrocodone bitartrate ER (Hysingla ER)-was considered covered if it was listed on the health plan's formulary. Generalized linear models were used to assess the association between ADF opioid formulary coverage and the study outcomes. RESULTS: Of 1,350,607 eligible patients, those enrolled in health plans with coverage of ADF opioids were more likely to fill a prescription for an ADF opioid than those enrolled in plans that did not cover ADF opioids. The risk for opioid abuse or overdose was significantly lower among patients enrolled in plans with broader ADF coverage (adjusted odds ratio [OR], 0.91; 95% confidence interval [CI], 0.86-0.95 for oxycodone HCl CR only vs no ADF coverage; adjusted OR, 0.70; 95% CI, 0.67-0.73 for oxycodone HCl CR plus ≥1 ADF opiods vs no ADF; adjusted OR, 0.77; 95% CI, 0.73-0.81 for oxycodone HCl CR plus ≥1 ADF opiods vs oxycodone HCl CR only; all P <.0001). Approximately 15% and 25% reductions in the opioid abuse or overdose-related hospitalization rate and medical costs were observed for those in the oxycodone HCl CR plus ≥1 ADF opioids coverage group versus those without ADF opioid coverage. CONCLUSIONS: Broad formulary coverage of ADF opioids is associated with reduced rates of opioid abuse or overdose in real-world managed care populations. Health plan administrators and policymakers may consider improving the formulary coverage of ADF opioids as a strategy to ensure appropriate patient access to necessary pain medications while mitigating risk for opioid abuse or overdose.

Healthcare Resource Use and Cost: The Impact of Adopting an Abuse-Deterrent Formulation of Extended Release Morphine.

BACKGROUND: Development of abuse-deterrent formulations (ADFs) of prescription opioids (RxO) is an important step toward reducing misuse and abuse. Morphine-ARER (MorphaBond™ ER) is an extended-release (ER) morphine sulfate tablet formulated to deter misuse/abuse via intravenous (IV) and intranasal (IN) routes of administration. OBJECTIVE: A model was developed to estimate the budget impact to a hypothetical commercial health plan of 10 million members 2 years after adding morphine-ARER to drug formulary. METHODS: We analyzed incremental health care resource use (HCRU) associated with RxO misuse/abuse based on a health plan's RxO formulary coverage and patterns of misuse/abuse. Misuse/abuse rates, incremental HCRU and associated costs were based on the 2015 National Survey on Drug Use and Health, an analysis of claims from OptumHealth Care Solutions, Inc. (2013-2015) and published literature. RxO formulary shares were based on 2016-2017 Symphony Retail Prescription data. Morphine-ARER was assumed to capture 20 and 30 percent from branded and 0.3 and 0.6 percent from generic non-ADF ER morphine, in the first and second years, respectively. Proportions of misuse/abuse deterred by physical/chemical properties of morphine-ARER were assumed to be 90 percent via IV and 60 percent via IN administration, with further IN deterrence based on results from morphine-ARER's human abuse liability study. RESULTS: Adding morphine-ARER to formulary resulted in a potential decrease in abuse-related healthcare costs by $557,321 (-$0.00232 per-member per-month [PMPM]), offsetting a pharmacy cost increase of $217,045 (+$0.00090 PMPM), resulting in net cost-savings of $0.00142 PMPM over 2 years, based on certain model assumptions. CONCLUSION: Placing morphine-ARER on a health plan's drug formulary may result in reduced misuse/abuse and overall cost savings.

Importance of Initial Complete Parenteral Iron Repletion on Hemoglobin Level Normalization and Health Care Resource Utilization: A Retrospective Analysis.

STUDY OBJECTIVE: Iron deficiency anemia is the most common form of anemia, and parenteral iron therapy is necessary in select patients. The objective of this analysis was to assess the impact of initial complete parenteral iron repletion on serum hemoglobin (Hgb) level normalization and on health care resource utilization in real-world practice. DESIGN: Retrospective observational study. DATA SOURCE: Decision Resources Group Real-World Data Repository (United States databases). PATIENTS: A total of 2966 patients who had a baseline Hgb level below normal (< 12 g/dl for females and < 13.5 g/dl for males) and were treated with parenteral iron between March 2015 and February 2017. MEASUREMENTS AND MAIN RESULTS: The effect of receiving the required parenteral iron dose to replete the deficit, calculated by a modified Ganzoni formula, within 3 weeks of the first parenteral iron therapy claim (index date) on the likelihood of Hgb level normalization, was estimated by using logistic regression. All analyses were adjusted for sex, age, comorbidities, and use of prescription oral iron therapy. The adjusted mean numbers of all-cause inpatient admissions, outpatient visits, and emergency department (ED) visits within 6 months and 1 year after the index date were compared between patients with and without normalized Hgb levels by using negative binomial regression. Of the 2966 included patients, 33.9% received the required iron dose within 3 weeks of the index date, and 19.6%, 48.2%, and 53.9% had a normalized Hgb level within 8 weeks of the index date, within 1 year of the index date, and until the end of data availability, respectively. Patients who received the required iron dose within 3 weeks of the index date were significantly more likely to have a normalized Hgb level within 8 weeks of the index date and at any time during the study period than those who did not: adjusted odds ratio (OR) (95% confidence interval [CI]) 2.67 (2.20, 3.24) and 2.33 (1.96, 2.77), respectively. Hgb level normalization within 1 year of the index date was associated with fewer inpatient admissions and outpatient visits and a similar number of ED visits compared with no Hgb level normalization 1 year after the index date. CONCLUSION: The results of these analyses underscore the importance of initial complete parenteral iron repletion for rapidly improving clinical outcomes. Prompt achievement of a normalized Hgb level may also provide an opportunity to reduce health care resource utilization in patients with iron deficiency anemia receiving parenteral iron therapy.

Analysis of Real-World Dosing Patterns for the 3 FDA-Approved Medications in the Treatment of Fibromyalgia.

BACKGROUND: Fibromyalgia is a chronic condition characterized by widespread pain, fatigue, and sleep disturbances that affects approximately 2% to 4% of the adult population in the United States, with minimal real-world data related to the use of medications and associated dosages for this condition. OBJECTIVE: To analyze the real-world dosing patterns of the 3 medications approved by the US Food and Drug Administration for fibromyalgia-pregabalin, duloxetine, and milnacipran. METHODS: Using QuintilesIMS' (now IQVIA) electronic medical record data linked to administrative claims, we identified adults with fibromyalgia who were newly prescribed pregabalin, duloxetine, or milnacipran between January 1, 2006, and December 31, 2014. We summarized and compared the starting and maximum doses with United States prescribing information (USPI) dosing recommendations. RESULTS: In all, 1043 patients who were receiving pregabalin, 1281 receiving duloxetine, and 326 patients receiving milnacipran with similar age and comorbidity profiles were included in the study. The mean starting dose was 176 mg daily, 56 mg daily, and 95 mg daily for pregabalin, duloxetine, and milnacipran, respectively. More patients receiving pregabalin (35%) had a starting dose lower than recommended compared with patients receiving duloxetine (7%) or milnacipran (17%; P <.0001). Of the patients who received pregabalin, 27% had USPI-recommended maintenance dosing versus 91% of patients who received duloxetine and 80% who received milnacipran (P <.0001). The mean duration of treatment was longer for duloxetine (205 days; P <.0001) than for pregabalin (167 days) and milnacipran (167 days). The duration of using the maximum dose of each medication as a percentage of the total time of medication use was 77% for pregabalin, 84% for duloxetine, and 90% for milnacipran (P <.0001). CONCLUSIONS: Patients using pregabalin were the most likely of the 3 cohorts to receive lower than label-recommended starting doses and the least likely to receive the recommended maintenance doses during follow-up compared with those receiving duloxetine or milnacipran. Real-world prescribing patterns indicate that factors other than label recommendations may be influencing prescribed dosing.

Comparison of claims vs patient-reported adherence measures and associated outcomes among patients with nonvalvular atrial fibrillation using oral anticoagulant therapy.

OBJECTIVE: To compare oral anticoagulant (OAC) adherence among patients with nonvalvular atrial fibrillation (NVAF) using patient-reported and claims-based measures, and to evaluate the effect of OAC adherence on health care costs and patient satisfaction with OAC therapy. METHODS: This was a hybrid US observational study consisting of a longitudinal cohort survey followed by linkage and analysis of respondents' administrative claims data. Patients with NVAF receiving warfarin, dabigatran, rivaroxaban, or apixaban completed an initial survey and follow-up surveys at 4, 8, and 12 months. Patient-reported adherence was measured at each survey by Morisky Medication Adherence Scale (MMAS-8) and pharmacy claims-determined adherence by the proportion of days covered (PDC) for the 12-month period following the initial survey date; adherence was defined as MMAS-8 score =8 and PDC ≥80%. Patient satisfaction with OAC therapy was assessed by the Duke Anticoagulation Satisfaction Scale (DASS). RESULTS: Overall, 675 patients completed at least the initial survey (warfarin, n=271; dabigatran, n=266; rivaroxaban, n=128; apixaban, n=10). Fewer than half (47.9%) were PDC adherent, 37.2% were MMAS-8 adherent, and 19.4% were adherent by both measures. Total medical costs of PDC-adherent patients were significantly lower vs PDC-nonadherent patients (US$640 vs $993 per-patient per-month, respectively, p<0.05). MMAS-8-adherent patients reported higher treatment satisfaction; total DASS score was significantly lower among MMAS-8-adherent than MMAS-8-nonadherent patients (37.3 vs 42.9, respectively, p<0.001). CONCLUSION: Using claims-based or patient-reported methods to measure OAC adherence may lead to different results when assessing impact on health care costs and satisfaction with anticoagulation medication. These results underscore the importance of considering both claims-based and patient-reported measures when evaluating treatment adherence in real-world settings.

Effect of Renal Function on Dosing of Non-Vitamin K Antagonist Direct Oral Anticoagulants Among Patients With Nonvalvular Atrial Fibrillation.

BACKGROUND: Non-vitamin K antagonist direct oral anticoagulants (DOACs) are fixed-dose regimens indicated for stroke prevention in nonvalvular atrial fibrillation (NVAF) patients. Dose adjustment is necessary among patients with renal insufficiency to optimize efficacy and safety. OBJECTIVE: To assess DOAC dosing appropriateness and its effect on clinical outcomes in NVAF patients. METHODS: Adult NVAF patients with ≥1 DOAC pharmacy claim (January 1, 2013, to December 31, 2014), continuous enrollment for ≥12 months post-index DOAC claim, and documented creatinine clearance within 3 months preindex date in the Optum/Humedica SmartFile database were eligible. DOAC dosage was classified as inappropriate or appropriate by level of renal function, age, and body weight per US prescription information. Cox proportional models were used to assess the risks of bleeding and stroke associated with inappropriate DOAC dosage. RESULTS: Of the 388 eligible patients, 69 (17.8%) were inappropriately dosed, and rivaroxaban had the highest inappropriate dosing rate. Most inappropriately dosed patients were underdosed. Inappropriately dosed patients were more likely to be older, female, and have a body weight of ≤60 kg; they also had higher mean CHA2DS2-VASc and Charlson comorbidity index scores (all P < 0.05). Overtreated patients had a higher risk of bleeding (hazard ratio [HR] = 5.4; P = 0.006) than undertreated patients (HR = 3.1; P = 0.025) relative to appropriately dosed patients. However, no significant difference in stroke risk was observed, most likely because very few stroke events were observed in the study. CONCLUSIONS: Inappropriate dosing occurred among patients with normal and insufficient renal function. The consideration of clinical factors beyond renal function is necessary to reduce bleeding risk associated with DOAC therapy.

Illness perceptions and burden of disease in fibromyalgia.

INTRODUCTION: Fibromyalgia (FM) is a chronic syndrome that usually develops midlife. It is associated with a high burden of illness that causes significant disability. Areas covered: Diagnosis can be challenging, given the diverse clinical presentation among those with FM. Therefore, the typical health care journey for a patient with FM is lengthy and complex. There is no acknowledged treatment algorithm for FM, prescribing patterns vary markedly, and patients are likely to receive suboptimal or inappropriate pharmacotherapy. Expert commentary: Major improvements in FM recognition and management are urgently needed. Long-term prospective studies should be conducted to improve the understanding of the course of illness and to determine whether early diagnosis and intervention can reduce the severity and duration of symptoms.

Health Care Utilization and Costs Associated with Nausea and Vomiting in Patients Receiving Oral Immediate-Release Opioids for Outpatient Acute Pain Management.

INTRODUCTION: Nausea and vomiting (NV) are common side effects of opioid use and limiting factors in pain management. This study sought to quantify the frequency of antiemetic prescribing and the impact of NV on health care resource utilization and costs in outpatients prescribed opioids for acute pain. The perspective was that of a commercial health plan. METHODS: Medical and pharmacy claims from IMS PharMetrics Plus were used to identify patients initiating opioid therapy with a prescription for an oxycodone-, hydrocodone- or codeine-containing immediate-release product for acute use (≤15-day supply) between October 1, 2013 and September 30, 2014. Patients with a medical claim for NV (International Classification of Diseases, Ninth Revision, Clinical Modification codes 787.0x), with or without an antiemetic prescription fill, were compared with patients with no NV claim or antiemetic prescription fill to assess differences in all-cause health care utilization and costs over 1 month. Propensity score matching (PSM) was used to adjust for between-group differences in baseline patient characteristics. RESULTS: The co-prescribing of opioids with antiemetic agents was 10.2%. After PSM (n = 45,790 per group), patients with NV claims had significantly more hospitalizations (11.5% vs 4.2%), emergency department visits (65.0% vs 12.1%), and physician office visits (85.2% vs 64.5%) compared with patients with no NV claims (all P < 0.0001). Mean total health care costs were higher among patients with a NV claim versus those without evidence of the side effect ($6290 vs $2309; P < 0.0001). Among patients with a recent hospitalization, patients with NV claims had higher rates of 30-day rehospitalization than those with no NV claims (24.4% vs 3.0%; P < 0.0001). CONCLUSIONS: Among outpatients prescribed opioids for management of acute pain, co-prescribing with antiemetics was low, and the economic burden associated with NV was high. Efforts to prevent NV in patients receiving opioid therapy may improve patient outcomes and provide cost savings to the health care system. FUNDING: Daiichi Sankyo, Inc.

Review of the cost of venous thromboembolism.

BACKGROUND: Venous thromboembolism (VTE) is the second most common medical complication and a cause of excess length of hospital stay. Its incidence and economic burden are expected to increase as the population ages. We reviewed the recent literature to provide updated cost estimates on VTE management. METHODS: Literature search strategies were performed in PubMed, Embase, Cochrane Collaboration, Health Economic Evaluations Database, EconLit, and International Pharmaceutical Abstracts from 2003-2014. Additional studies were identified through searching bibliographies of related publications. RESULTS: Eighteen studies were identified and are summarized in this review; of these, 13 reported data from the USA, four from Europe, and one from Canada. Three main cost estimations were identified: cost per VTE hospitalization or per VTE readmission; cost for VTE management, usually reported annually or during a specific period; and annual all-cause costs in patients with VTE, which included the treatment of complications and comorbidities. Cost estimates per VTE hospitalization were generally similar across the US studies, with a trend toward an increase over time. Cost per pulmonary embolism hospitalization increased from $5,198-$6,928 in 2000 to $8,764 in 2010. Readmission for recurrent VTE was generally more costly than the initial index event admission. Annual health plan payments for services related to VTE also increased from $10,804-$16,644 during the 1998-2004 period to an estimated average of $15,123 for a VTE event from 2008 to 2011. Lower costs for VTE hospitalizations and annualized all-cause costs were estimated in European countries and Canada. CONCLUSION: Costs for VTE treatment are considerable and increasing faster than general inflation for medical care services, with hospitalization costs being the primary cost driver. Readmissions for VTE are generally more costly than the initial VTE admission. Further studies evaluating the economic impact of new treatment options such as the non-vitamin K antagonist oral anticoagulants on VTE treatment are warranted.

Systematic review and network meta-analysis of the relative efficacy and safety of edoxaban versus other nonvitamin K antagonist oral anticoagulants among patients with nonvalvular atrial fibrillation and CHADS2 score ⩾ 2.

BACKGROUND: The nonvitamin K antagonist oral anticoagulants pivotal clinical trials for stroke prevention in atrial fibrillation have important differences in trial designs and baseline patient characteristics. OBJECTIVE: We sought to evaluate the relative efficacy and safety of edoxaban versus other nonvitamin K antagonist oral anticoagulants in the management of stroke prevention in atrial fibrillation by adjusting for differences in baseline stroke risk and the length of follow-up among the four phase 3 randomized controlled trials. METHODS: We conducted a systematic literature review of randomized controlled trials evaluating the nonvitamin K antagonist oral anticoagulants for stroke prevention in atrial fibrillation and performed a network meta-analysis using data from ENGAGE AF-TIMI 48, RE-LY, ROCKET-AF, and ARISTOTLE, with warfarin as a common comparator. To adjust for between-trial differences in CHADS2 score and length of follow-up, annualized event rates among patients with CHADS2 score ⩾ 2 were analyzed using a mixed Poisson's regression model. RESULTS: Once-daily high-dose edoxaban was associated with significant lower major bleeding episodes compared with once-daily rivaroxaban (risk ratio, 0.76; 95% confidence interval, 0.66-0.89), twice-daily dabigatran 150 mg (risk ratio, 0.78; 95% confidence interval, 0.61-0.84), and twice-daily dabigatran 110 mg (risk ratio, 0.83; 95% confidence interval, 0.71-0.98) and similar bleeding risk compared with twice-daily apixaban (risk ratio, 1.08; 95% confidence interval, 0.91-1.28). Risk of stroke and systemic embolism was similar for the high-dose edoxaban and other nonvitamin K antagonist oral anticoagulant regimens. The low-dose edoxaban regimen was associated with a significant lower risk of major bleeding than other nonvitamin K antagonist oral anticoagulants and a significant higher risk of stroke and systemic embolism compared with apixaban and dabigatran 150 mg. CONCLUSION: Among patients with atrial fibrillation and CHADS2 score ⩾ 2, the high-dose edoxaban regimen may offer similar efficacy to the other nonvitamin K antagonist oral anticoagulants but with a significant major bleeding benefit over rivaroxaban and dabigatran.

The economic burden of ischemic stroke and major hemorrhage in medicare beneficiaries with nonvalvular atrial fibrillation: a retrospective claims analysis.

BACKGROUND: Understanding the economic implications of oral anticoagulation therapy requires careful consideration of the risks and costs of stroke and major hemorrhage. The majority of patients with atrial fibrillation (AF) are aged ≥65 years, so focusing on the Medicare population is reasonable when discussing the risk for stroke. OBJECTIVE: To examine the relative economic burden associated with stroke and major hemorrhage among Medicare beneficiaries who are newly diagnosed with nonvalvular atrial fibrillation (NVAF). METHODS: This study was a retrospective analysis of a 5% sample of Medicare claims data for patients with NVAF from 2006 to 2008. Patients with NVAF without any claims of AF during the 12 months before the first (index) claim for AF in 2007 (baseline period) were identified and were classified into 4 cohorts during a 12-month follow-up period after the index date. These cohorts included (1) no claims for ischemic stroke or major hemorrhage (without stroke or hemorrhage); (2) no claims for ischemic stroke and ≥1 claims for major hemorrhage (hemorrhage only); (3) ≥1 claims for ischemic stroke and no major hemorrhage claims (stroke only); and (4) ≥1 claims each for ischemic stroke and for major hemorrhage (stroke and hemorrhage). The 1-year mean postindex total all-cause healthcare costs adjusted by the Centers for Medicare & Medicaid Services Hierarchical Condition Categories (HCC) score were compared among the study cohorts. RESULTS: Of the 9455 eligible patients included in this study, 3% (N = 261) of the patients had ischemic stroke claims only, 3% (N = 276) had hemorrhage claims only, and <1% (N = 13) had both during the follow-up period. The unadjusted follow-up healthcare costs were $63,781 and $64,596 per patient for the ischemic stroke only and the hemorrhage only cohorts, respectively, compared with $35,474 per patient for those without hemorrhage or stroke claims. After adjustment for HCC risk score, the mean incremental costs for patients with stroke claims only and hemorrhage claims only, relative to those without stroke or hemorrhage claims, were $26,776 (95% confidence interval [CI], $20,785-$32,767; P <.001) and $26,168 (95% CI, $20,375-$31,961; P <.001), respectively. CONCLUSION: The economic burden of managing patients with NVAF who experience ischemic stroke and hemorrhage were similarly significant during the first year after a diagnosis of NVAF. The burden of major bleeding complications on patients, clinicians, and payers should not be overlooked, and these complications should be considered in conjunction with the cost-savings associated with ischemic stroke risk reduction in future cost-benefit evaluations of oral anticoagulation therapy.

Characteristics affecting oral anticoagulant therapy choice among patients with non-valvular atrial fibrillation: a retrospective claims analysis.

BACKGROUND: Dabigatran is one of the three newer oral anticoagulants (OACs) recently approved in the United States for stroke prevention in non-valvular atrial fibrillation (NVAF) patients. The objective of this study was to identify patient, healthcare provider, and health plan factors associated with dabigatran versus warfarin use among NVAF patients. METHODS: Administrative claims data from patients with ≥ 2 NVAF medical claims in the HealthCore Integrated Research Database between 10/1/2009 and 10/31/2011 were analyzed. During the study intake period (10/1/2010 - 10/31/2011), dabigatran patients had ≥ 2 dabigatran prescriptions, warfarin patients had ≥ 2 warfarin and no dabigatran prescriptions, and the first oral anticoagulant (OAC) prescription date was the index date. Continuous enrollment for 12 months preceding ("pre-index") and ≥ 6 months following the index date was required. Patients without pre-index warfarin use were assigned to the 'OAC-naïve' subgroup. Separate analyses were performed for 'all-patient' and 'OAC-naïve' cohorts. Multivariable logistic regression (LR) identified factors associated with dabigatran versus warfarin use. RESULTS: Of 20,320 patients (3,019 dabigatran and 17,301 warfarin) who met study criteria, 27% of dabigatran and 13% of warfarin patients were OAC-naïve. Among all-patients, dabigatran patients were younger (mean 67 versus 73 years, p < 0.001), predominantly male (71% versus 61%, p < 0.001), and more frequently had a cardiologist prescriber (51% versus 30%, p < 0.001) than warfarin patients. Warfarin patients had higher pre-index Elixhauser Comorbidity Index (mean: 4.3 versus 4.0, p < 0.001) and higher ATRIA bleeding risk score (mean: 3.0 versus 2.3, p < 0.001). LR results were generally consistent between all- and OAC-naïve patients. Among OAC-naïve patients, strongest factors associated with dabigatran use were prescriber specialty (OR = 3.59, 95% CI 2.68-4.81 for cardiologist; OR = 2.22, 95% CI 1.65-2.97 for other specialist), health plan type (OR = 1.47 95% CI 1.10-1.96 for preferred provider organization), and prior ischemic stroke (OR = 1.42, 95% CI 1.06-1.90). Older age decreased the probability of dabigatran use. CONCLUSIONS: Beside patient characteristics, cardiology specialty of the prescribing physician and health plan type were the strongest factors associated with dabigatran use.

Utilization of parenteral anticoagulants and warfarin: impact on the risk of venous thromboembolism recurrence in the outpatient setting.

BACKGROUND: Clinical guidelines recommend parenteral anticoagulation therapy with an early initiation of warfarin therapy for the treatment of patients with acute venous thromboembolism (VTE) and the prevention of recurrence. OBJECTIVES: To evaluate the outpatient utilization of parenteral anticoagulant therapy and warfarin among patients with VTE, and to examine the effects of parenteral anticoagulant use and the time to warfarin initiation from VTE diagnosis on the risk for VTE recurrence. METHODS: The Truven Health MarketScan Commercial Claims Database was used to identify patients aged 18 to 64 years who had an outpatient claim for deep-vein thrombosis or pulmonary embolism between January 2010 and December 2011 (ie, index date) and had no VTE diagnosis or treatment during the 12 months before the index date, had no hospital or emergency department VTE claim within 7 days after the index outpatient VTE claim, and had received warfarin <30 days after the index date. A recurrent VTE event was defined as a VTE-related emergency department visit or hospitalization within 8 to 365 days after the index date. A Cox proportional hazards model was used to estimate the adjusted hazard ratio (HR) associated with VTE recurrence risk related to parenteral anticoagulant use and warfarin initiation timing. RESULTS: A total of 5820 patients were included in the study (mean age, 50.5 years); of these, 45% were female. A total of 75.7% (4403) of the patients receiving warfarin also received a parenteral anticoagulant, and the median time from VTE diagnosis to warfarin initiation was 5 days for parenteral anticoagulant users compared with 11 days for nonusers. Parenteral anticoagulant use was associated with a 49% recurrent VTE risk reduction (HR, 0.51; 95% confidence interval [CI], 0.43-0.60; P <.001). Each day of delayed warfarin initiation from the diagnosis of acute VTE was associated with a 1% increase in the risk for VTE recurrence (HR, 1.01; 95% CI, 1.01-1.02; P = .003). CONCLUSIONS: Overall, 1 in 4 patients with VTE who had received warfarin in the outpatient setting did not receive parenteral anticoagulation therapy. Among those who received warfarin, its initiation was not always timely, despite its positive effects on reducing VTE recurrence. These findings highlight the potential quality-of-care concerns associated with the failure to use or the delayed implementation of guideline-recommended VTE treatment, and the need to improve compliance with clinical guidelines in the treatment of patients with VTE.

The costs of warfarin underuse and nonadherence in patients with atrial fibrillation: a commercial insurer perspective.

BACKGROUND: Atrial fibrillation (AF) imposes a substantial clinical and economic burden on the U.S. health care system. Despite national guidelines that recommend oral anticoagulation for stroke prevention, the literature consistently reports its underuse in AF patients with moderate to high stroke risk. OBJECTIVE: To assess the economic burden of underuse and nonadherence of warfarin therapy among patients with nonvalvular AF in a commercially insured population. METHODS: Claims data between January 2003 and December 2007 from the Thomson Reuters MarketScan Research Database were used. Patients diagnosed with nonvalvular AF who were continuously enrolled for at least 12 months prior to and 2 months following their diagnosis, who had a CHADS2 score ≥ 2, and were not at high risk of bleeding (ATRIA score less than 5, HEMORR2HAGE score less than 4, and HAS-BLED score less than 3) at baseline were included. Patients were followed for up to 18 months after the AF diagnosis date to assess the level of warfarin utilization. Health care resource utilization and cost during follow-up among patients with the proportion of days covered (PDC) by warfarin greater than 0.8 (high) and ≤ 0.8 (low) versus patients with no warfarin exposure were assessed. Multivariate negative binomial regressions and generalized linear models were used to estimate differences in resource utilization and cost, respectively. RESULTS: Of the 13,289 subjects included in this analysis, 47% had no warfarin exposure; 31.5% had low PDC; and 21.5% had high PDC. The rates of ischemic stroke and transient ischemic attack (per 100 patient-years) were significantly lower for the groups that had high and low PDCs as compared with the group with no warfarin exposure (P less than 0.001). Multivariate analysis showed that patients with high PDC were 27% less likely (P less than 0.001) to incur hospitalizations, and 16% were less likely (P = 0.019) to incur emergency room visits than patients who did not receive warfarin, but the differences between low PDC patients and no warfarin exposure were not significant. Although both low and high PDC were associated with lower all-cause inpatient cost (P less than 0.001), only high PDC was associated with a lower post-index all-cause total cost (P less than 0.001) compared with no warfarin exposure. CONCLUSION: Our results confirm that underutilization and nonadherence of warfarin among nonvalvular AF patients is both prevalent and costly. Warfarin use among patients with moderate to high stroke risk and low to moderate bleed risk demonstrated a stroke benefit without a significant increase in intracranial hemorrhage. Adherence to oral anticoagulant therapy was associated with a significant reduction in inpatient service use and total health care cost. Improving adherence to oral anticoagulation is important to attaining the clinical and economic benefits of therapy.