Early impact of guideline publication on angiotensin-receptor neprilysin inhibitor use among patients hospitalized for heart failure.

BACKGROUND: On May 20, 2016, US professional organizations in cardiology published joint treatment guidelines recommending the use of angiotensin-receptor neprilysin inhibitor (ARNI) for eligible patients with heart failure with reduced ejection fraction (HFrEF). Using data from the Get With The Guidelines-Heart Failure registry, we evaluated the early impact of this update on temporal trends in ARNI prescription. METHODS: We analyzed patients with HFrEF who were eligible for ARNI prescription (EF ≤40%, no contraindications) and hospitalized from February 20, 2016, through August 19, 2016-allowing for 13weeks before and after guideline publication. We quantified trends in ARNI use associated with guidelines publication with an interrupted time-series design using logistic regression and accounting for correlations within hospitals using general estimating equation methods. RESULTS: Of 7,200 eligible patient hospitalizations, 51.9% were discharged in the period directly preceding publication of the guidelines, and 48.1% were discharged after. Odds ratios of ARNI prescription at discharge were significantly higher in the postguideline period compared with the preguideline period in adjusted models (adjusted odds ratio 1.29, 95% CI 1.06-1.57, P=.01). However, there was no significant interaction between observed and expected ARNI use after guideline publication (Pinteraction=.14). Results were consistent using a 6-month before and after time frame. CONCLUSIONS: The model suggested a small increase in ARNI use in HF patients being discharged from the hospital immediately after guideline release. However, the publication of national guidelines recommending ARNI use seemed to have little influence on the adoption of this evidence-based medication in the first 3 to 6months.

Incidence of skin and soft tissue infections in ambulatory and inpatient settings, 2005-2010.

BACKGROUND: The emergence of community-associated methicillin-resistant S. aureus was associated with dramatically increased skin and soft tissue infection (SSTI) incidence in the first few years of the 21(st) century in the U.S. However, subsequent trends are poorly understood. METHODS: We examined ambulatory and inpatient data of over 48 million persons years aged 0-64 years from the HealthCore Integrated Research Database (HIRD) between 2005 and 2010. Data were extracted from medical, pharmacy, and eligibility databases. We quantified SSTI incidence, type, and complications and comparative incidence trends for urinary tract infections (UTIs) and pneumonia. RESULTS: A total of 2,301,803 SSTIs were identified. Most SSTIs (95 %) were treated in the ambulatory setting and most (60 %) were categorized as abscesses or cellulitis. During the study period, SSTI incidence remained relatively stable from 47.9 (95 % CI: 47.8-48.1) cases/1,000 PY in 2005 to 48.5 cases/1,000 PY (95 % CI: 48.3-48.6) in 2010). Persons aged 45-64 years had the highest incidence of both ambulatory-treated and inpatient-treated SSTIs (51.2 (95 % CI: 51.1-51.3) and 3.87 (95 % CI: 3.84-3.90) cases/1,000 PY, respectively). SSTI complications such as myositis, gangrene, and sepsis occurred in 0.93 % (95 % CI: 0.92-0.94 %) and 16.92 % (95 % CI: 16.87-16.97 %) of ambulatory-treated and inpatient-treated patients, respectively. SSTI incidence was approximately twice that of UTIs and tenfold of that of pneumonia. CONCLUSIONS: Among our large, diverse population of persons less than 65 years, SSTI incidence 2005 through 2010 has remained relatively constant at approximately 4.8 SSTIs per 100 person years, suggesting that previously observed increases in SSTI incidence remain sustained.

Predicting medication persistence to buprenorphine transdermal system.

OBJECTIVES: Persistence, the duration a patient remains on therapy, in chronic, symptomatic conditions plays an important role in therapy effectiveness. Understanding the duration and patient factors associated with prescribed medication persistence is, therefore, an important step toward better treatment and health outcomes for patients. In the following study, an analysis of such factors associated with buprenorphine transdermal system (BTDS) persistence was conducted utilizing a large US private practitioner and pharmacy claims database and is herein reported. METHODS: Patients aged ≥ 18 years initiating BTDS during January 1, 2011-November 30, 2011 were identified in the IMS Private Practitioner Medical Claims and Pharmacy Claims databases. An index date was defined as the first prescription of BTDS during the studied interval. During the preindex period, Charlson Comorbidity Index (CCI), chronic pain-related conditions, and prior medication use were assessed. Concomitant medications and various treatment patterns (eg, last dose strength and dose adjustments) were assessed in the postindex 6-month period. Persistence was measured as the duration of BTDS from initiation to the 1st >28-day refill gap in the postindex 6-month period. Descriptive statistical and survival analysis was used to assess the predictors of BTDS persistence. RESULTS: During the study period, 10,457 patients newly treated with BTDS were identified. Patients' mean (± SD) age was 54.5 (± 15.2) years; 69.9% were women, and the mean (± SD) CCI was 1 (± 1.4). Utilizing a hierarchical approach, patients were separated into different cohorts based on the initial analgesic prescription identified during postindex period with 91.7%, 34.7%, and 59.0% of the patients using opioids, NSAIDs and adjuvant analgesics, respectively. Multivariate regression analyses showed that patients with prior opioid and adjuvant analgesic use were 21% and 5% less likely to discontinue BTDS (P < 0.05), respectively, as compared to patients not using these agents. Patients with concomitant use of adjuvant analgesics were 15% less likely to discontinue therapy (P < 0.05) as compared to patients without concomitant use of these agents. Long-term BTDS persistence was also observed in patients who had a dose change or a last dose strength >5 mcg/hour. Sensitivity analyses for those with 30-day prior opioid use and patients with ≥ 2 claims of BTDS confirmed these findings. CONCLUSIONS: Prior and concomitant use of adjuvant analgesics, prior use of opioids, and dose adjustments were associated with significantly longer persistence among patients initiating BTDS. The results suggest that patients are less likely to discontinue BTDS early if practitioners account for prior treatment history and dose titration.

Real-world Use of Mogamulizumab Among Patients With Mycosis Fungoides and Sézary Syndrome Before and During COVID-19 in the United States.

PURPOSE: During the coronavirus disease 2019 (COVID-19) pandemic, professional organizations suggested extending dosing intervals for systemic cancer therapies to limit in-person visits. Mogamulizumab, indicated for adults with relapsed or refractory mycosis fungoides (MF) or Sézary syndrome (SS) after ≥1 prior systemic therapy, should be administered every 7 days of the first 28-day cycle (loading) and every 14 days of each subsequent cycle (maintenance) according to the approved prescribing information in the United States (US). This study examined the real-world use of mogamulizumab before and during the COVID-19 pandemic in the US. METHODS: Using Symphony Health's Integrated Dataverse (IDV) database, adults with ≥1 diagnosis of MF or SS and ≥1 mogamulizumab claim between October 1, 2018 and December 22-, 2022 were identified. Patients in MF and SS cohorts were divided into 3 subgroups based on the date they initiated mogamulizumab treatment: pre-COVID-19 (October 1, 2018-March 31, 2020), COVID-19 Phase 1 (April 1, 2020-July 31, 2021), and COVID- 19 Phase 2 (August 1, 2021-December 22, 2022). FINDINGS: During the study, 270 patients with MF and 337 patients with SS initiated mogamulizumab. The pre-COVID-19, COVID-19 Phase 1, and COVID-19 Phase 2 subgroups included 95, 81, and 94 patients with MF and 124, 119, and 94 patients with SS, respectively. In the MF cohort, mean loading dosing intervals were 13, 12, and 9 days for the pre-COVID-19, COVID-19 Phase 1, and COVID-19 Phase 2 subgroups, respectively, and mean maintenance dosing intervals were 16, 16, and 16 days, respectively. In the SS cohort, mean loading dosing intervals were 16, 11, and 11 days, and mean maintenance dosing intervals were 19, 18, and 16 days, respectively. For both cohorts, more patients in the COVID-19 Phase 1 and Phase 2 subgroups than in the pre-COVID-19 subgroup had gaps of ≤10 days between loading doses and ≤21 days between maintenance doses. IMPLICATIONS: In patients with MF and SS, loading dosing intervals in the pre-COVID-19 period were longer than the loading schedule per the approved prescribing information, but there was a trend towards closer concordance in the COVID-19 periods. Maintenance dosing intervals in patients with MF were consistently similar to the approved schedule across treatment periods, and in patients with SS became more closely aligned over time. Thus, dosing intervals for mogamulizumab in both loading and maintenance cycles do not appear to have been extended during the COVID-19 Phase 1 and Phase 2 periods compared with the pre-COVID-19 period, despite recommendations to extend dosing intervals for systemic cancer therapies during COVID-19.

A Retrospective Cohort Study to Determine Real-World Treatment Patterns in Patients with Sézary Syndrome in the United States.

INTRODUCTION: Sézary syndrome (SS) is a rare leukemic cutaneous T cell lymphoma. This study was conducted to examine the real-world treatment patterns among patients with SS in the USA from 2018 to 2020. METHODS:  This was a retrospective cohort study using the Symphony Health Solutions claims database. Adult patients with ≥ 1 diagnosis code for SS were classified into three non-mutually exclusive cohorts: 2018, 2019, and 2020. Patient characteristics and treatment patterns were examined across the 3 years of study and reported descriptively for each year. Annual treatment patterns were also described for the five states with the highest proportions of SS patients in 2020. RESULTS: Overall, 869, 882, and 853 SS patients were identified in 2018, 2019, and 2020, respectively (median age: 70 years for each year; male: 54.4%, 54.8%, and 55.6%, respectively). The use of any systemic and parenteral systemic treatments increased over time. While utilization rates for many specific systemic therapies decreased over the study period, mogamulizumab use increased, making it the most commonly used systemic treatment in 2020 (29.2%) among patients with any systemic treatment. The five states with the highest proportions of SS patients in 2020 were Florida, New York, California, Texas, and Pennsylvania. Systemic treatment patterns varied considerably by state. CONCLUSION: Some systemic therapies showed decreased usage over time while a few showed increased utilization, with mogamulizumab showing the largest increase. Treatment patterns for SS varied by region. Further research is needed to examine the factors that drive treatment selection for patients with SS.

Healthcare use and costs before and after parathyroidectomy in patients on dialysis.

BACKGROUND: Parathyroidectomy (PTX) is often performed in dialysis patients when medical treatment fails to control secondary hyperparathyroidism (SHPT). PTX is viewed by many as a cost-containing measure for patients who have been treated with vitamin D analogs and calcimimetics. Yet, information about health resource utilization and costs before and after PTX is limited. METHODS: This retrospective cohort study used professional service and pharmacy claims to identify subjects on dialysis undergoing PTX from 1/1/2008-12/31/2010. Only subjects with at least six months of information before and after PTX were considered. Subjects with primary hyperparathyroidism or kidney transplant were excluded. Prescription use, physician encounters, and surgical complications were compared during the six months immediately before and after PTX. RESULTS: The mean (SD) age of the 181 study subjects was 51 (15) years; 59% female; and 80% insured by Medicare. Overall, the percentage of patients receiving medications to manage altered mineral metabolism increased from 67% before to 79% after PTX. Specifically, oral vitamin D use increased, while the utilization of cinacalcet decreased resulting in mean (SD) monthly medication charges decreasing from $486 (507) to $226 (288) (p < 0.01). The mean (SD) number of physician encounters rose from 15 (14) before to 21 (22) per 6 months after PTX (p < 0.01) resulting in the corresponding increase in mean (SD) monthly charges from $1531 (2150) to $1965 (3317) (p = 0.08). Hypocalcemia was the predominant diagnosis recorded for post-surgical physician encounters occurring in 31% of all subjects; 84% of hypocalcemic episodes were managed in acute care facilities. CONCLUSIONS: The cost of medications to manage SHPT decreased after PTX largely due to reduction in cinacalcet use, whereas vitamin D use increased likely to manage hypocalcemia. The frequency and cost of physician encounters, especially in acute care settings, were higher in the 6 months after PTX attributable largely to episodes of severe hypocalcemia. Overall, the reduction in prescription costs during the 6 months after PTX is outweighed by the higher costs associated with physician care.

Accuracy of identifying neutropenia diagnoses in outpatient claims data.

PURPOSE: Diagnosis codes have been valid tools to identify severe neutropenia leading to hospitalization in claims data, but no data exist on the accuracy of outpatient diagnosis of neutropenia. We examined the validity and accuracy of claims-based algorithms to identify neutropenia from outpatient visits. METHODS: Adults with outpatient diagnosis of neutropenia in the HealthCore Integrated Research Database™ were identified by several algorithms using a combination of International Classification of Diseases, 9th Revision (ICD-9) codes and drug use data. We calculated sensitivity, specificity, positive predictive value (PPV), and negative predictive value of these algorithms using outpatient laboratory data within 3 months of the diagnosis as the gold standard to ascertain cases of mild (absolute neutrophil count (ANC) <1,500/µL) and severe (ANC <500/µL) neutropenia. RESULTS: Among 95,742 eligible subjects, 867 patients were identified with any ICD-9 codes for neutropenia. This algorithm had high specificity (99%), but low sensitivity (9%) and PPV (18%) for mild neutropenia. Among the subjects identified with the ICD-9 288.0 (N = 203), sensitivity was 4% and PPV was 33%. Specificity and PPV of the algorithm that combined any ICD-9 codes for neutropenia with dispensing of pegfilgrastim or filgrastim were 100 and 56% for mild neutropenia, respectively. Sensitivity was 1%. All algorithms had slightly higher sensitivity, but lower PPV for severe neutropenia. CONCLUSIONS: Use of ICD-9 codes for neutropenia in combination with drug use data did not appear to accurately identify outpatient diagnosis of neutropenia without using laboratory results, but it may be useful in determining the absence of neutropenia in claims data.

Lower Hospitalization and Healthcare Costs With Sacubitril/Valsartan Versus Angiotensin-Converting Enzyme Inhibitor or Angiotensin-Receptor Blocker in a Retrospective Analysis of Patients With Heart Failure.

Background Outcomes data among patients with heart failure (HF) with reduced ejection fraction treated with sacubitril/valsartan ( SAC / VAL ) are largely limited to clinical trial results. We compared hospitalization and healthcare costs among real-world patients with HF with reduced ejection fraction treated with SAC / VAL versus angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker ( ACEI / ARB ). Methods and Results Using retrospective administrative claims data, stable patients with HF with reduced ejection fraction treated with SAC / VAL or ACEI / ARB from October 2015 to June 2016 were identified. Postindex hospitalization and healthcare costs were assessed in propensity-matched cohorts using robust variance estimation. Time to first hospitalization was modeled using unadjusted Kaplan-Meier estimates and multivariable models. Postindex all-cause healthcare costs were modeled using an adjusted multivariable model. Among 279 patients per matched cohort, postindex hospitalization risk was lower for SAC / VAL compared with ACEI / ARB using Kaplan-Meier estimation and unadjusted Cox models. For HF hospitalization, the hazard ratio (95% CI) was 0.56 (0.33-0.94; P=0.030). Adjusted results were similar to unadjusted. Mean ( SD ) monthly healthcare costs were lower for SAC / VAL versus ACEI / ARB for all categories except pharmacy, with hospital costs being particularly disparate between cohorts: for HF hospitalization, $248 ($1588) for SAC / VAL versus $1122 ($7290) for ACEI / ARB . The adjusted risk of incurring increased all-cause postindex costs was lower for SAC / VAL versus ACEI / ARB (cost ratio [95% CI] 0.74 [0.59-0.94]; P=0.013). Conclusions In clinical practice, patients with HF with reduced ejection fraction treated with SAC / VAL were less likely to be hospitalized than matched patients treated with ACEI / ARB . Despite higher pharmacy costs, SAC / VAL -treated patients incurred lower monthly medical and total healthcare costs.

Development, psychometric evaluation, and initial feasibility assessment of a symptom tracker for use by patients with heart failure (HFaST).

BACKGROUND: This study aimed to develop and provide a psychometric and feasibility pilot evaluation of the Heart Failure (HF) Symptom Tracker (HFaST), a new patient-reported tool designed to facilitate communication between patients and health care providers (HCPs) in routine clinical care. The HFaST enables patients to identify worsening HF symptoms, with a long-term goal of preventing hospitalizations or emergency room visits. METHODS: The HFaST was developed drawing on evidence from the literature, qualitatively with cognitive interviews (12 patient/caregiver and 8 HCPs), and evaluated quantitatively (psychometric, feasibility assessment). The HFaST was administered for 7 consecutive days to 100 individuals diagnosed with HF during a multisite, non-interventional US pilot study. Health care providers then completed a survey assessing the feasibility and importance of the HFaST in clinical practice. Qualitative development included a literature review and cognitive interviews with patients, caregivers, and HCPs. The psychometric properties of the HFaST were evaluated using classical test theory methods. Descriptive statistics provided insight into HCPs' perceptions of the feasibility of using the HFaST in clinical practice. RESULTS: A preliminary set of 40 items was developed for the symptom tracker and iteratively reduced to 10 items based on the qualitative phase. Test-retest reliability (weighted kappa 0.71-0.97), discriminating validity, and construct validity of the HFaST were acceptable. HCPs rated the HFaST as a good (70%) or excellent (30%) means of tracking HF symptoms. Six HFaST items were ultimately retained, covering concepts of fatigue, shortness of breath (3 items), swelling, and rapid weight gain. CONCLUSIONS: The 6-item HFaST is an easy-to-use tool designed to raise patients' awareness of HF symptoms and facilitate communication with HCPs. Future research should evaluate HFaST implementation in clinical practice and effectiveness as an intervention to potentially prevent hospitalizations and emergency room visits.

Relationship Between Hospital Characteristics and Early Adoption of Angiotensin-Receptor/Neprilysin Inhibitor Among Eligible Patients Hospitalized for Heart Failure.

Background The angiotensin-receptor/neprilysin inhibitor ( ARNI ) sacubitril/valsartan reduces hospitalization and mortality for patients with heart failure with reduced ejection fraction. However, adoption of ARNI into clinical practice has been slow. Factors influencing use of ARNI have not been fully elucidated. Using data from the Get With The Guidelines-Heart Failure registry, Hospital Compare, Dartmouth Atlas, and the American Hospital Association Survey, we sought to identify hospital characteristics associated with patient-level receipt of an ARNI prescription. Methods and Results We analyzed patients with heart failure with reduced ejection fraction who were eligible for ARNI prescription (ejection fraction≤40%, no contraindications) and hospitalized from October 1, 2015 through December 31, 2016. We used logistic regression to estimate the associations between hospital characteristics and patient ARNI prescription at hospital discharge, accounting for clustering of patients within hospitals using generalized estimating equation methods and adjusting for patient-level covariates. Of 16 674 eligible hospitalizations from 210 hospitals, 1020 patients (6.1%) were prescribed ARNI at discharge. The median hospital-level proportion of patients prescribed ARNI was 3.3% (Q1, Q3: 0%, 12.6%). After adjustment for patient-level covariates, for-profit hospitals had significantly higher odds of ARNI prescription compared with not-for-profit hospitals (odds ratio, 2.53; 95% CI , 1.05-6.10; P=0.04), and hospitals located in the Western United States had lower odds of ARNI prescription compared with those in the Northeast (odds ratio, 0.33; 95% CI , 0.13-0.84; P=0.02). Conclusions Relatively few hospital characteristics were associated with ARNI prescription at hospital discharge, in contrast to what has been observed in early adoption in other disease areas. Additional evaluation of barriers to implementing new evidence into heart failure practice is needed.

Characteristics of early sacubitril/valsartan patients and considerations for studies in electronic health record data.

AIM: We examined characteristics of early sacubitril/valsartan users in a large US electronic health records database. PATIENTS & METHODS: We identified three cohorts of patients with heart failure (HF): sacubitril/valsartan patients with a prior HF diagnosis; patients with HF with reduced ejection fraction; and patients with HF treated with an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker and a ß-blocker. RESULTS: Sacubitril/valsartan patients were younger than patients in the other cohorts; the mean age of sacubitril/valsartan patients increased by 2 years in the first 15 months of marketing. Most sacubitril/valsartan patients had prior use of HF treatment. CONCLUSION: Overall, sacubitril/valsartan patients resembled those in the HF with reduced ejection fraction cohort, and commonly used other drugs for HF.

Home-Time After Discharge Among Patients Hospitalized With Heart Failure.

BACKGROUND: Surveys of patients with cardiovascular disease have suggested that "home-time"-being alive and out of any health care institution-is a prioritized outcome. This novel measure has not been studied among patients with heart failure (HF). OBJECTIVES: This study sought to characterize home-time following hospitalization for HF and assess its relationship with patient characteristics and traditionally reported clinical outcomes. METHODS: Using GWTG-HF (Get With The Guidelines-Heart Failure) registry data, patients discharged alive from an HF hospitalization between 2011 and 2014 and ≥65 years of age were identified. Using Medicare claims, post-discharge home-time over 30-day and 1-year follow-up was calculated for each patient as the number of days alive and spent outside of a hospital, skilled nursing facility (SNF), or rehabilitation facility. RESULTS: Among 59,736 patients, 57,992 (97.1%) and 42,153 (70.6%) had complete follow-up for home-time calculation through 30 days and 1 year, respectively. The mean home-time was 21.6 ± 11.7 days at 30 days and 243.9 ± 137.6 days at 1 year. Contributions to reduced home-time varied by follow-up period, with days spent in SNF being the largest contributor though 30 days and death being the largest contributor through 1 year. Over 1 year, 2,044 (4.8%) patients had no home-time following index hospitalization discharge, whereas 8,194 (19.4%) had 365 days of home-time. In regression models, several conditions were associated with substantially reduced home-time, including chronic obstructive pulmonary disease, renal insufficiency, and dementia. Through 1 year, home-time was highly correlated with time-to-event endpoints of death (tau = 0.72) and the composite of death or HF readmission (tau = 0.59). CONCLUSIONS: Home-time, which can be readily calculated from administrative claims data, is substantially reduced for many patients following hospitalization for HF and is highly correlated with traditional time-to-event mortality and hospitalization outcomes. Home-time represents a novel, easily measured, patient-centered endpoint that may reflect effectiveness of interventions in future HF studies.

Quantifying the relative importance to patients of avoiding symptoms and outcomes of heart failure.

OBJECTIVE: To evaluate heart failure (HF) patients' disease knowledge and preferences for avoiding different disease outcomes. METHODS: An online survey was administered to 400 individuals with a self-reported diagnosis of HF to elicit relative importance weights (RIWs) for avoiding 11 potential HF symptoms and outcomes using best-worst scaling. The survey also included questions about individuals' HF knowledge, and demographic and disease-experience characteristics. Differences in RIWs among sub-groups, defined by HF knowledge, caregiver support, age, recent hospitalization or emergency room visit for HF, health-related quality-of-life, and cardiac device experience were examined. RESULTS: Relative to limitations in usual activities (RIW 1.00), respondents preferred avoiding severe, infrequent cardiovascular events (e.g. stroke [RIW 8.51], heart transplant [RIW 7.84], or heart attack [RIW 5.3]) most, followed by difficulty breathing (RIW 2.55), inability to enjoy life (RIW 1.84), cardiac device implantation (RIW 1.74), and atrial fibrillation (RIW 1.57). Patients preferred avoiding swelling (RIW 0.47) and fatigue (RIW 0.58) least. RIWs for avoiding severe, infrequent events were higher among those with high disease knowledge, those without caregivers, and those without a recent hospitalization or emergency room visit. CONCLUSIONS: Patients' preferences for avoiding HF outcomes vary across outcomes and by individuals' knowledge, caregiver status, and age. Healthcare providers should solicit and incorporate insights about patients' knowledge of HF and their preferences for avoiding HF outcomes into HF education and management planning efforts.

Pharmacotherapy Choice Is Associated with 2-Year Mortality for Patients with Heart Failure and Reduced Ejection Fraction.

INTRODUCTION: Factors associated with mortality for patients with heart failure and reduced ejection fraction (HFrEF) are known; however, the association between initial pharmacotherapy (IPT) and mortality is unclear in real-world settings. METHODS: Using a retrospective design and claims database, 14,359 Medicare patients with HFrEF from August 2010 to July 2015 were identified. Index date was first HF claim. IPT was mono- or combo-angiotensin-converting enzyme inhibitor (ACEI), angiotensin II receptor blocker (ARB), beta-blocker (BB), hydralazine-nitrate (HN), and aldosterone antagonist (AA) within 1 year post-index. A multivariable time-dependent Cox model estimated associations between IPT and 2-year all-cause mortality. RESULTS: Patients' median age was 76 (70-82) years; 45.1% were female. Within 1 month post-index, 61.4% had IPT, 6.1% started after the first month, and 32.4% had no IPT in the first year. Of IPTs, 47.5% were mono-vasodilators (ACEI, ARB or HN), 23.3% mono-vasodilator + BB, 16.9% mono-BB, and 3.5% triple therapy [(ACEI or ARB) + BB + (HN or AA)]. Two-year mortality rate was 27.9%. Compared to mono-vasodilator therapy, patients initiating triple therapy had 29.3% lower risk of 2-year mortality; those on mono-BB or no IPT had higher mortality risk. CONCLUSION: IPT was associated with decreased 2-year mortality risk. Timely consideration of triple IPT therapies may be warranted once HFrEF diagnosis is confirmed. FUNDING: Novartis Pharmaceuticals Corp. located in East Hanover, NJ, USA.

Comparative healthcare costs in patients with metastatic melanoma in the USA.

Recent advances have increased treatment options for, and improved clinical outcomes in, metastatic melanoma (mM). Using a large claims database, this retrospective study compared healthcare and adverse event (AE) costs in a US managed care population of mM patients initiating vemurafenib (VEM), ipilimumab (IPI), dacarbazine (DTIC), paclitaxel (PAC), or temozolomide (TMZ) from July 2009 to September 2012. Treatment episodes were identified from the start of study drugs (index date) to a switch to a different study drug, or a gap greater than 45 days (>112 days for IPI). Grade 3/4 adverse events occurring ≥5% from study drug package inserts were selected for this analysis. All-cause costs for treatment episodes and AEs were normalized as monthly costs. Generalized estimating equation models with log link and gamma distribution provided adjusted monthly treatment episode and AE costs. A total of 809 treatment episodes were identified in 541 mM patients, with a mean (SD) age of 57.5 (11.5) years. The total mean (SD) all-cause cost per treatment episode for VEM was $77 687 ($60 329), for IPI was $153 062 ($134 048), for DTIC was $35 243 ($33 641), for TMZ was $42 870 ($41 384), and for PAC was $58 991 ($81 306). The adjusted mean monthly treatment episode cost for VEM was significantly lower than that for IPI and comparable to that for other drugs. VEM had a significantly lower monthly AE cost than IPI, DTIC, and PAC. In combination with safety and efficacy findings, these results may assist clinicians, patients, policy makers, and payers in the treatment of mM.

Lipid attainment among patients newly treated with lipid-altering drugs.

OBJECTIVE: Guidelines for preventing and treating patients with coronary artery disease have traditionally focused on reducing low-density lipoprotein cholesterol (LDL-C). Current treatments are effective; however, previous studies have identified a significant proportion of patients that are not achieving the recommended lipid levels. New guidelines were introduced November 2013. The objective of this study was to examine recent practice patterns and factors related to initiating treatment for hypercholesterolemia, which provides a comparative baseline to the introduction of new guidelines. RESEARCH DESIGN AND METHODS: We conducted a retrospective cohort analysis utilizing laboratory results of lipid profiles and medical claims from January 2007 to September 2011 to identify patients with elevated LDL-C and diagnoses of hypercholesterolemia without prior pharmacotherapy. Pharmacotherapy dispensed, treatment modifications, LDL-C-goal attainment, and potential drug intolerance were evaluated. RESULTS: Overall, among newly treated patients, 70.9% achieved the recommended LDL-C level within the first year of treatment; however, only 19.4% of those with coronary heart disease (CHD) or CHD risk equivalents achieved the more aggressive LDL-C goal of <70 mg/dL (1.8 mmol/L). LDL-C goals were generally achieved with the use of statins; however, a majority of patients underwent treatment modification(s) (e.g., discontinuation or restart). More than half of the patients diagnosed with elevated LDL-C did not initiate pharmacotherapy. LIMITATIONS: Data was unavailable for inpatient hospitalizations, family history of cardiovascular diseases, body weight, and height, and likely under-reporting of smoking within claims data. CONCLUSIONS: Newly treated patients with elevated LDL-C results generally achieved the recommended and risk-specific LDL-C goal with the use of lipid-altering drugs; however, there still exists a notable population of patients with CHD or CHD risk equivalents who were not treated to goal and a significant number of patients who do not receive lipid-lowering pharmacotherapy. New therapies and prescribing practices are warranted to adequately address these two patient populations.

US practitioner prescribing practices and patient characteristics of those newly treated with a buprenorphine transdermal patch system.

OBJECTIVES: Medication prescribing information provides guidance to healthcare providers on how to prescribe a drug properly. Oftentimes patient factors in addition to the prescribing information are considered when selecting medications. Utilizing real-world pharmacy and medical claims data, this study assessed US practitioner prescribing practices of US approved transdermal buprenorphine system (BTDS) in relation to BTDS's full prescribing information (FPI) as well as the relationship between patient factors and initial BTDS dose. RESEARCH DESIGN AND METHODS: Patients aged ≥18 years initiating BTDS between 1 January 2011 and 30 November 2011 were identified in the IMS Pharmacy and Private Practitioner Medical Claims databases. The index date was defined as the first filled BTDS prescription. Demographics, chronic pain-related medical conditions in the 12 months pre-index and prior medication use in the 6 months pre-index were assessed. Initial BTDS dosing strength, receipt of approved initial BTDS dose per the FPI, and concomitant medications were assessed in the post-index 6 month period. RESULTS: The study included 10,457 patients newly treated with BTDS. The majority of patients were female (69.9%) with a mean (±SD) age of 54.5 (±15.2) years. Within the 6 months prior to the index BTDS prescription, 91.7% of the patients used opioids. Overall, 48.9% of patients were prescribed the FPI approved BTDS dose. When stratified, 73.5% of opioid-naïve patients received the FPI approved initial dose compared to 46.0% of those with prior opioid experience of ≤80 mg morphine-equivalent daily dose. Patients on BTDS alone (i.e. monotherapy) had a higher rate of receiving the FPI approved initial BTDS dose compared to patients on BTDS concomitant regimens (p < 0.05). CONCLUSIONS: Practitioners demonstrated that they prescribe in accordance with BTDS's prescribing information in the majority of opioid-naïve patients and in approximately half of opioid-experienced patients. The initial opioid dose is a critical step in treatment, setting the stage for preventing side-effects and improving treatment effectiveness. Understanding practitioner prescribing practices with regard to the initial dose selection of BTDS may provide insight on how to improve outcomes of care and reduce healthcare resource utilization and costs associated with pain management. LIMITATIONS: Data obtained from prescription claims reflect only the activities of prescriptions filled, not medication use or other clinical characteristics observed by physicians when treating patients.

TSAT is a better predictor than ferritin of hemoglobin response to Epoetin alfa in US dialysis patients.

Clinical guidelines recommend concurrent treatment of anemia in end-stage renal disease with erythropoiesis-stimulating agents (ESAs) and iron. However, there are mixed data about optimal iron supplementation. To help address this gap, the relationship between iron markers and hemoglobin (Hb) response to ESA (Epoetin alfa) dose was examined. Electronic medical records of 1902 US chronic hemodialysis patients were analyzed over a 12-month period between June 2009 and June 2010. The analysis included patients who had at least one Hb value during each 4-week interval for four consecutive intervals (k - 2, k - 1, k, and k + 1; k is the index interval), received at least one ESA dose during intervals k - 1 or k, had at least one transferrin saturation (TSAT) value at interval k, and at least one ferritin value during intervals k - 2, k - 1, or k. Effect modification by TSAT and ferritin on Hb response was evaluated using the generalized estimating equations approach. Patients had a mean (standard deviation) age of 62 (15) years; 41% were Caucasian, 34% African American, 65% had hypertension, and 39% diabetes. Transferrin saturation, but not ferritin, had a statistically significant (P < 0.05) modifying effect on Hb response. Maximum Hb response was achieved when TSAT was 34%, with minimal incremental effect beyond these levels. Of the two standard clinical iron markers, TSAT should be used as the primary marker of the modifying effect of iron on Hb response to ESA. Long-term safety of iron use to improve Hb response to ESA warrants further study.

Anemia management trends in hospital-based dialysis centers (HBDCs), 2010 to 2013.

BACKGROUND: Few data have been reported on anemia management practices in hospital-based dialysis centers (HBDCs), which are uniquely different from other freestanding dialysis centers. Examining data from HBDCs would help determine if HBDCs and the general US dialysis population have similar trends related to how anemia is managed in dialysis patients. OBJECTIVE: Given recent changes in the prescribing information of erythropoiesis-stimulating agents (ESAs) and in end-stage renal disease-related health policy and reimbursement, this study describes trends in anemia management practices in HBDCs from January 2010 through March 2013. METHODS: Electronic medical records of 5404 adult hemodialysis patients in 50 US-based HBDCs were analyzed retrospectively. Patients included in the study cohort were aged ≥18 years and had at least 1 hemoglobin (Hb) measurement and 1 dose of an ESA between January 2010 and March 2013. End points included Hb concentration, darbepoetin alfa dosing, epoetin alfa dosing, and iron biomarkers (transferrin saturation and ferritin) and dosing. RESULTS: From 2010 to 2013, mean monthly Hb levels declined from 11.4 to 10.7 g/dL; the percentage of patients with mean monthly Hb levels <10 g/dL increased from 11.3% to 24.4%; and the percentage of patients with mean monthly Hb levels >12 g/dL declined from 30.1% to 11.2%. The median darbepoetin alfa cumulative 4-week dose also declined 38.8%, and the weekly epoetin alfa dose declined 24%. From January 2010 to March 2013, the percentage of patients with transferrin saturation >30% increased from 35.8% to 43.6%, the percentage of patients with ferritin levels >500 ng/mL increased from 62.0% to 77.9%, the percentage of patients with ferritin levels ≥800 ng/mL increased from 28.9% to 47.3%, and the median cumulative 4-week intravenous iron dose increased 50%. CONCLUSIONS: These study results support growing evidence that meaningful changes have occurred over the last 3 years in how anemia is clinically managed in US hemodialysis patients. Study limitations include that changes in patient clinical/demographic characteristics over time were not controlled for and that study findings may not be applicable to HBDCs that have different patient populations and/or do not use an electronic medical record system. Continuing to evaluate anemia management practices in HBDCs would provide additional information on the risks and benefits of anemia care. Consistent with national data, the findings from this study indicate that from 2010 to 2013, HBDCs modified anemia management practices for dialysis patients, as evidenced by reductions in mean monthly Hb levels and ESA dosing and by increases in iron biomarkers and dosing.

Incidence of death and recurring acute coronary syndrome after stopping clopidogrel therapy in a large commercially-insured population in the US.

BACKGROUND/OBJECTIVE: Guidelines support clopidogrel therapy in medically-treated or percutaneous coronary intervention (PCI) patients after hospitalization for acute coronary syndrome (ACS). However, clopidogrel discontinuation has been associated with increased short-term risks. This study evaluated the risk of adverse outcomes (AOs), defined as death or recurrent ACS, after clopidogrel discontinuation in a managed-care population. METHODS: ACS patients (n = 7625) with ≥1 clopidogrel pharmacy claim from 2001 to 2006 and no AO before discontinuing clopidogrel were identified from administrative claims data. AO occurrences were recorded at 90-day intervals following clopidogrel discontinuation. RESULTS: The mean (SD) duration of clopidogrel therapy for medically-treated, bare metal stent (BMS) and drug eluting stent (DES) patients was 349.2 (393.1) days, 235.6 (383.0) days, and 280.2 (227.1) days, respectively. Among medically-treated patients, Poisson regression analysis showed a 2.19 times higher AO risk (p < 0.01), a 1.63 times greater risk among BMS patients (p < 0.01), and a 1.56 times greater risk for DES patients (p ≥ 0.05) during days 0-90 versus days 91-180 after clopidogrel discontinuation. Sensitivity analysis showed that medically-treated, BMS and DES patients with ≤90 days of clopidogrel therapy had 2.13, 1.68 and 2.40 times higher AO risk, respectively, during days 0-90 versus 91-180 after discontinuation. No significant elevated AO risk was observed after discontinuation in patients on clopidogrel for 91-270 days. Limitations included those associated with the use of administration claims date, the absence of clinical data and lack of knowledge of aspirin use. CONCLUSIONS: Patients who discontinued clopidogrel therapy were at high risk of death or recurrent ACS during the first 90 days. AO risks following discontinuation appeared elevated in patients with ≤90 days of clopidogrel therapy versus those with >90 days of treatment.