Cost-effectiveness of andexanet alfa versus four-factor prothrombin complex concentrate for the treatment of oral factor Xa inhibitor-related intracranial hemorrhage in the US.

AIM: To conduct a cost-effectiveness analysis (CEA) on the use of andexanet alfa for the treatment of factor Xa inhibitor-related intracranial hemorrhage (ICH) from the US third-party payer and societal perspectives. METHODS: CEA compared andexanet alfa to prothrombin complex concentrate for the treatment of patients receiving factor Xa inhibitors admitted to hospital inpatient care with an ICH. The model comprised two linked phases. Phase 1 utilized a decision tree to model the acute treatment phase (admission of a patient with ICH into intensive care for the first 30 days). Phase 2 modeled long-term costs and outcomes using three linked Markov models comprising the six health states defined by the modified Rankin score. RESULTS: The analysis showed that the strategy of using andexanet alfa for the treatment of factor Xa inhibitor-related ICH is cost-effective, with incremental cost-effectiveness per quality-adjusted life-year gained of $35,872 from a third-party payer perspective and $40,997 from a societal perspective over 20 years. LIMITATIONS: (1) Absence of head-to-head trials comparing therapies included in the economic model, (2) lack of comparative long-term data on treatment efficacy, and (3) bias resulting from the study designs of published literature. CONCLUSION: Given these results, the use of andexanet alfa for the reversal of anticoagulation in patients with factor Xa inhibitor-related ICH may improve quality of life and is likely to be cost-effective in a US context.

Effects of Epoetin Alfa Titration Practices, Implemented After Changes to Product Labeling, on Hemoglobin Levels, Transfusion Use, and Hospitalization Rates.

BACKGROUND: Little is known about epoetin alfa (EPO) dosing at dialysis centers after implementation of the US Medicare prospective payment system and revision of the EPO label in 2011. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Approximately 412,000 adult hemodialysis patients with Medicare Parts A and B as primary payer in 2009 to 2012 to describe EPO dosing and hemoglobin patterns; of these, about 70,000 patients clustered in about 1,300 dialysis facilities to evaluate facility-level EPO titration practices and patient-level outcomes in 2012. PREDICTOR: Facility EPO titration practices when hemoglobin levels were <10 and >11g/dL (grouped treatment variable) determined from monthly EPO dosing and hemoglobin level patterns. OUTCOMES: Patient mean hemoglobin levels, red blood cell transfusion rates, and all-cause and cause-specific hospitalization rates using a facility-based analysis. MEASUREMENTS: Monthly EPO dose and hemoglobin level, red blood cell transfusion rates, and all-cause and cause-specific hospitalization rates. RESULTS: Monthly EPO doses declined across all hemoglobin levels, with the greatest decline in patients with hemoglobin levels < 10g/dL (July-October 2011). In 2012, nine distinct facility titration practices were identified. Across groups, mean hemoglobin levels differed slightly (10.5-10.8g/dL) but within-patient hemoglobin standard deviations were similar (∼0.68g/dL). Patients at facilities implementing greater dose reductions and smaller dose escalations had lower hemoglobin levels and higher transfusion rates. In contrast, patients at facilities that implemented greater dose escalations (and large or small dose reductions) had higher hemoglobin levels and lower transfusion rates. There were no clinically meaningful differences in all-cause or cause-specific hospitalization events across groups. LIMITATIONS: Possibly incomplete claims data; excluded small facilities and those without consistent titration patterns; hemoglobin levels reported monthly; inferred facility practice from observed dosing. CONCLUSIONS: Following prospective payment system implementation and labeling revisions, EPO doses declined significantly. Under the new label, facility EPO titration practices were associated with mean hemoglobin levels (but not standard deviations) and transfusion use, but not hospitalization rates.

Epoetin Alfa and Outcomes in Dialysis amid Regulatory and Payment Reform.

Erythropoiesis-stimulating agents (ESAs) are commonly used to treat anemia in patients with CKD, including those receiving dialysis, although clinical trials have identified risks associated with ESA use. We evaluated the effects of changes in dialysis payment policies and product labeling instituted in 2011 on mortality and major cardiovascular events across the United States dialysis population in an open cohort study of patients on dialysis from January 1, 2005, through December 31, 2012, with Medicare as primary payer. We compared observed rates of death and major cardiovascular events in 2011 and 2012 with expected rates calculated on the basis of rates in 2005-2010, accounting for differences in patient characteristics and influenza virulence. An abrupt decline in erythropoietin dosing and hemoglobin concentration began in late 2010. Observed rates of all-cause mortality, cardiovascular mortality, and myocardial infarction in 2011 and 2012 were consistent with expected rates. During 2012, observed rates of stroke, venous thromboembolic disease (VTE), and heart failure were lower than expected (absolute deviation from trend per 100 patient-years [95% confidence interval]: -0.24 [-0.08 to -0.37] for stroke, -2.43 [-1.35 to -3.70] for VTE, and -0.77 [-0.28 to -1.27] for heart failure), although non-ESA-related changes in practice and Medicare payment penalties for rehospitalization may have confounded the results. This initial evidence suggests that action taken to mitigate risks associated with ESA use and changes in payment policy did not result in a relative increase in death or major cardiovascular events and may reflect improvements in stroke, VTE, and heart failure.

Anemia management practice patterns in small dialysis organizations following implementation of the prospective payment system.

BACKGROUND: The impact of the United States Prospective Payment System (PPS) "bundle payment system" on anemia management within small dialysis organizations (SDOs) was studied to evaluate the financia burden on SDOs. METHODS: Facilities enrolled in the original study on SDOs were grouped into three hemoglobin (Hb) categories by subject-months: > 25% of subjectmonths with Hb < 10 g/dL (sub-10); > 25% of subject-months with Hb > 12 g/dL (super-12); remaining facilities (10 - 12 group). Subjectlevel data aggregated to facility level for Hb concentration, intravenous (IV) epoetin ± (EA) dose per administration, dose titration, and EA administration frequency during the baseline and follow-up periods were described. RESULTS: Baseline demographic characteristics were imbalanced between the sub-10 (n = 7) and super-12 facilities (n = 5). Mean (SD) Hb concentrations were similar for sub-10 (11.1 (3.0) g/dL) and super-12 (11.6 (2.2) g/dL) facilities during the baseline period, but differed during the follow-up period (10.4 (2.7) vs. 11.4 (2.3) g/dL). The median (Q1, Q3) EA IV dose per administration during follow-up was 3,726 (3,467, 3,961) and 5,712 (4,816, 7,324) units in the sub-10 and super-12 facilities, respectively. A small trend toward upward titration was seen. CONCLUSIONS: Results suggest a difference in anemia management between sub-10 and super-12 facilities during the first year of PPS implementation. Future analyses evaluating patterns of reimbursement and shifts in clinical practice guidelines are warranted globally.

Temporal trends in fracture rates and postdischarge outcomes among hemodialysis patients.

Patients with ESRD have a substantially increased risk of bone fractures, but the burden of fractures has not been sufficiently characterized in this population. Here, we analyzed fracture rates and postdischarge outcomes using Medicare data from hemodialysis patients in the United States between 2000 and 2009. We assessed adjusted quarterly fracture rates (inpatient and outpatient) and consequences of postfracture hospitalization for seven categories of fracture location. Pelvis/hip, vertebral, and lower leg fractures were the most prevalent fracture types. Pelvis/hip fractures declined slightly from 29.6 to 20.6 per 1000 patient-years between early 2000 and late 2009, but the incidence rates for all other fracture types remained relatively constant. Median lengths of stay for the primary fracture hospitalization ranged from 5 days (interquartile range [IQR], 3-9 days) for forearm/wrist fractures to 8 days (IQR, 5-12 days) for femur fractures. The proportion of patients discharged from the primary hospitalization to a skilled-nursing facility ranged from 28% (ribs/sternum) to 47% (pelvis/hip). A negative binomial regression model suggested that patients had an adjusted mean of 3.8-5.2 additional hospitalizations during the year after discharge from the index hospitalization, varying by fracture type, comprising a mean of 33-52 inpatient days. Case-mix-adjusted mortality rates after discharge ranged from 0.43 to 0.91 per patient-year and were highest for vertebral, pelvis/hip, and femur fractures. In conclusion, fractures in the dialysis population are common and are associated with a substantially increased risk for death and hospitalization.