Comparing Healthcare Resource Utilization and Costs in HFPEF patients using SGLT2-inhibitor Combination Treatments: A Retrospective Claims Analysis

Abstract

Background: Heart failure with preserved ejection fraction (HFpEF) represents an increasingly significant clinical burden. Recent treatment guidelines recommend sodium-glucose cotransporter-2 inhibitors (SGLT2i) as foundational therapy, with the addition of either mineralocorticoid receptor antagonists (MRAs) or angiotensin receptor-neprilysin inhibitors (ARNIs) as adjunctive therapy. However, real-world evidence comparing healthcare resource utilization (HCRU) and costs between these combination therapies remains limited. Methods: We conducted a retrospective cohort study using the Merative™ MarketScan® commercial and Medicare databases from 2019 to 2023 to compare HCRU and costs in adult patients (≥18 years) with HFpEF initiating SGLT2i+MRA vs. SGLT2i+ARNI. Patients required SGLT2i usage and continuous enrollment for 12 months pre- and post-index. Those using both MRA and ARNI concurrently were excluded. Outcomes assessed over 12 months post-initiation included inpatient (IP), emergency department (ED), outpatient (OP) services, and pharmacy costs. Multivariable regression models adjusted for demographic and clinical covariates. Results: The study included 2,128 patients (1,418 MRA, 710 ARNI). Adjusted analyses showed that the ARNI group experienced significantly lower HCRU, including 9% fewer IP admissions (IRR, 0.91; 95% CI, 0.84-0.98; p=0.015), 20% shorter IP length of stay (IRR, 0.80; 95% CI, 0.72-0.89; p<0.001), 12% fewer ED visits (IRR, 0.88; 95% CI, 0.79-0.98; p=0.0164), and 11% fewer OP service days (IRR, 0.89; 95% CI, 0.84-0.95; p<0.001). Unadjusted mean total healthcare costs were modestly lower in the ARNI group compared to the MRA group, driven by reduced IP, ED, OP, and total costs, despite slightly higher pharmacy costs largely attributable to differences in drug prices. However, no statistically significant differences were observed in adjusted total healthcare costs across settings. Conclusions: In this real-world analysis, adjunctive ARNI therapy was associated with reduced HCRU but did not translate into lower overall healthcare costs compared to MRA-based combination therapy. These findings highlight the importance of considering both utilization patterns and drug costs when selecting combination treatments for HFpEF, supporting the need for individualized treatment strategies, particularly in patients with multiple comorbidities.