Contemporary economic burden in a real‐world heart failure population with Commercial and Medicare supplemental plans

Abstract Background Limited real‐world data exist on healthcare resource utilization (HCRU) and associated costs of patients with heart failure (HF) with reduced ejection fraction (HFrEF) and preserved EF (HFpEF), including urgent HF visits, which are assumed to be less burdensome than HF hospitalizations (hHFs) Hypothesis This study aimed to quantify the economic burden of HFrEF and HFpEF, via a retrospective, longitudinal cohort study, using IBM® linked claims/electronic health records (Commercial and Medicare Supplemental data only). Methods Adult patients, indexed on HF diagnosis (ICD‐10‐CM: I50.x) from July 2012 through June 2018, with 6‐month minimum baseline period and varying follow‐up, were classified as HFrEF (I50.2x) or HFpEF (I50.3x) according to last‐observed EF‐specific diagnosis. HCRU/costs were assessed during follow‐up. Results About 109 721 HF patients (22% HFrEF, 31% HFpEF, 47% unclassified EF; median 18 months' follow‐up) were identified. There were 3.2 all‐cause outpatient visits per patient‐month (HFrEF, 3.3; HFpEF, 3.6); 69% of patients required inpatient stays (HFrEF, 80%; HFpEF, 78%). Overall, 11% of patients experienced hHFs (HFrEF, 23%; HFpEF, 16%), 9% experienced urgent HF visits (HFrEF, 15%; HFpEF, 12%); 26% were hospitalized less than 30 days after first urgent HF visit versus 11% after first hHF. Mean monthly total direct healthcare cost per patient was $9290 (HFrEF, $11 053; HFpEF, $7482). Conclusions HF‐related HCRU is substantial among contemporary real‐world HF patients in US Commercial or Medicare supplemental health plans. Patients managed in urgent HF settings were over twice as likely to be hospitalized within 30 days versus those initially hospitalized, suggesting urgent HF visits are important clinical events and quality improvement targets.


| INTRODUCTION
Heart failure (HF) is an important cause of mortality and morbidity, 1 yet has broader health implications, including substantial economic burden on healthcare systems. In the context of shifting HF epidemiology with rising projected disease burden, safely curbing HF-related costs has emerged as a common goal for patients and healthcare systems. Patients may seek acute HF care in non-hospitalization settings, including emergency departments, HF clinics, observation units, urgent-care centers, and ambulatory infusion sites. 2,3 Increasing HF prevalence 4 is expected to drive HF-related direct costs to $53 billion by 2030. 5 Despite recognition of the economic burden of HF, limited data exist estimating the impact on healthcare resource utilization (HCRU) and direct medical costs of HF management across care settings. Even less information exists on cost and HCRU variation according to left ventricular ejection fraction (LVEF), specifically patients with HF with preserved ejection fraction (HFpEF) or reduced ejection fraction (HFrEF), despite increasing awareness of the burden of HFpEF. 6 The primary study aim was to estimate HCRU and associated direct medical costs, including HF hospitalizations (hHFs) and urgent HF visits, in a contemporary HF-patient cohort. Secondary aims were estimation of HCRU/costs by LVEF-specific diagnosis, and comparison of HCRU/cost outcomes by age and prior/recent inpatient stay.

| METHODS
This was a retrospective, longitudinal cohort study of a prevalent HF population using linked US claims and electronic healthcare records Patients with distinct forms of cardiomyopathy (ICD-9/10-CM 425.x/I42.x-43.x) during baseline were excluded. Patients were classified as HFrEF (ICD-9/10-CM 428.2x/I50.2x) or HFpEF (ICD-9/10-CM 428.3x/I50.3x) at indexing according to the last-observed LVEF-specific diagnosis during follow-up, including indexing, in the expectation that patients undergo further testing/examination over time, leading to greater ability to make LVEF-specific diagnoses. Patients without an LVEF-specific diagnosis (i.e., LVEF not measured/recorded) or ambiguously labeled (i.e., combined HFrEF/HFpEF diagnosis) were classified as HF with unclassified ejection fraction (HFuEF).
This retrospective analysis involved no decisions on patient interventions and patient-level data were anonymized. Institutional review board/ethics approval and patient informed consent were not required. All-cause HCRU and expenditures were reported by service type (inpatient, outpatient, and pharmaceutical). HCRU/costs associated with HF-related medications, hHFs, and urgent HF visits were derived separately. The hHFs were defined as hospitalizations with ≥1 overnight stay and primary diagnosis of HF. Urgent HF visits were defined as emergency department visits with HF as the primary diagnosis, but not constituting an hHF. Resource users were patients using ≥1 unit of a given healthcare service.
Two sensitivity analyses regarding LVEF status classification were conducted: (a) using diagnosis at index only, and (b) using lastobserved LVEF-specific diagnosis, omitting patients with conflicting LVEF-specific diagnoses during follow-up. These are described further in the Appendix S1.
The rate of outpatient visits was 3.2 per patient-month in the study cohort (HFrEF 3.3, HFpEF 3.6; Table 2). The most-visited outpatient service providers were acute-care hospitals (18% of single-day visits) and family practitioners (16%). Two-thirds (69%) of the study cohort required an inpatient stay; the rate of inpatient stays was 0.07 per patient-month and was comparable between HFrEF and HFpEF (both 0.08). HF was the most frequently recorded primary diagnosis across all inpatient stays (13% of stays); other diagnoses were "other sepsis" (6%), "acute myocardial infarction" (4%), and "atrial fibrillation and flutter" (4%). The mean (SD) length of stay (LoS) was 6.0 (6.3) days and mean (SD) inpatient LoS across entire follow-up was 14.3 (21.9) days; LoS did not differ substantially between HFrEF and HFpEF.
In total, 9% of patients had an urgent HF visit (HFrEF, 15%; HFpEF, 12%; Table 2). The rate of urgent HF visits among  Figure 2). Furthermore, 11% of all patients had an hHF during follow-up (HFrEF, 23%; HFpEF, 16%; Figure 2 HCRU by age is summarized in Table S1. LoS of hHFs was significantly longer in younger patients; these patients also had significantly shorter times to readmission than older patients. Total healthcare costs (all cause) and HF costs were also higher in younger patients.
Medication use was similar among patients who had and had not required hospitalization at baseline (data not shown). Outpatient visits and inpatient stays were more common in previously hospitalized patients; LoS was also significantly longer (Table S1). The number of urgent HF visits and hHFs was numerically similar across subgroups.
Previously hospitalized patients had higher total healthcare costs (all cause) compared with those not previously hospitalized, predominantly driven by inpatient stays and outpatient visits (Table S1).
HCRU and costs by underlying T2DM and CKD at indexing are summarized in Table S2. Mean total healthcare costs and many components of HCRU were significantly higher for patients with versus without T2DM or CKD.
Sensitivity analyses using index diagnosis only or excluding patients with conflicting LVEF-specific diagnoses during follow-up, produced similar results for cost data as primary study analyses ( Figure S3). Results were directionally consistent (i.e., higher for HFrEF vs. HFpEF), and numerically similar. The proportions of costs attributed to each setting were also consistent with primary analyses. Hospitalization also negatively impacts patients and families. 8,9 Although the economic cost of HF has been widely studied, few studies examined burden of HFpEF and HFrEF. HCRU and costs have been reported to be significantly greater in patients with chronic

| DISCUSSION
HFrEF after a worsening HF event versus patients who remain stable. 10 This study, undertaken to quantify the real-world economic bur- HFpEF, heart failure with preserved ejection fraction; HFrEF, heart failure with reduced ejection fraction; HFuEF, heart failure with unclassified ejection fraction; hHF, heart failure hospitalization settings. Nonetheless, we found that patients with a recent hospitali-

ACKNOWLEDGMENTS
Medical writing assistance was provided by Deirdre Carman, PhD, of Alispera Communications Ltd. This study, including medical writing assistance, was funded by AstraZeneca. The study funder contributed to the study design via development and critical review of a study protocol, data collection/acquisition, interpretation of the data, critical review of the study report, and development, critical review and decision to submit this article.