TOPLINE:

Despite receiving quadruple medical therapy at discharge, older patients in the US hospitalized for heart failure with reduced ejection fraction (HFrEF) had substantial risks for mortality, rehospitalizations, and significant healthcare costs, according to a brief report published in JAMA Cardiology.

METHODOLOGY:

• Researchers conducted a retrospective cohort study to evaluate 1-year clinical outcomes and healthcare costs in hospitalized patients with HFrEF who were prescribed quadruple medical therapy at discharge.
• They used data from a registry linked to Medicare claims data and included 20,651 patients aged 65 years or older who were hospitalized for HFrEF across multiple hospitals in the US between July 2021 and December 2023.
• Quadruple medical therapy included prescription of an angiotensin receptor-neprilysin (ARN) inhibitor, beta-blocker, mineralocorticoid receptor antagonist, and SGLT2 inhibitor at any dose at the time of hospital discharge.
• In another analysis, the definition of quadruple therapy was broadened to allow an angiotensin-converting enzyme (ACE) inhibitor, angiotensin receptor blocker (ARB), or ARN inhibitor.
• Researchers assessed the following clinical outcomes: all-cause mortality, hospitalization for HF, a composite of all-cause mortality or hospitalization for HF, and all-cause hospitalization. They also analyzed Medicare healthcare expenditures.

TAKEAWAY:

• A total of 1490 (7.2%) patients were discharged on quadruple therapy that included an ARN inhibitor, and 2438 (11.8%) received quadruple therapy that included an ACE inhibitor, ARB, or ARN inhibitor.
• Over 12 months, patients discharged on ARN inhibitor-based therapy had cumulative incidences of 19.3% for all-cause mortality, 26.0% for hospitalization for HF, 37.1% for all-cause mortality or hospitalization for HF, and 54.5% for all-cause hospitalization; broadening the definition of quadruple therapy yielded similar outcomes.
• Patients incurred a median of $27,956 per-patient healthcare costs over 12 months, with a mean cost of $51,337.
• Among patients discharged on ARN inhibitor-based therapy, 71.9% were hospitalized for worsening HFrEF, 27.4% were hospitalized with new-onset HFrEF, and 0.7% had unknown prior HF status.

IN PRACTICE:

“In this nationwide cohort study, even when prescribed quadruple medical therapy, older patients hospitalized for HFrEF in US clinical practice face substantial residual risk of death and readmission and often accrue high healthcare costs,” the researchers of the study wrote.

SOURCE:

This study was led by Stephen J. Greene, MD, Duke Clinical Research Institute in Durham, North Carolina. It was published online on January 28, 2026, as a brief report in JAMA Cardiology.

LIMITATIONS:

This study was restricted to patients aged 65 years or older, limiting generalizability. Researchers identified patients who were prescribed quadruple medical therapy at discharge but could not assess adherence to medications or dosing after discharge.

DISCLOSURES:

The HF registry was provided by the American Heart Association and was sponsored in part by various pharmaceutical and healthcare companies. Several authors reported receiving personal fees, honoraria for advisory or consultancy roles, and awards and/or grants and having other financial ties with multiple pharmaceutical companies. Multiple authors reported being employees of Cytokinetics, two of whom additionally reported holding stock in the company.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.