Cost-Effectiveness of Sodium-Glucose Co-Transporter-2 Inhibitors and Angiotensin Receptor-Neprilysin Inhibitors by Ejection Fraction and Drug Pricing in the United States: A Systematic Review
Abstract
Background: Sodium-glucose co-transporter 2 (SGLT2) inhibitors and angiotensin receptor-neprilysin inhibitors (ARNI) are heart failure (HF) therapies selected for price negotiations under the Inflation Reduction Act. This study aimed to summarize the cost-effectiveness of SGLT2 inhibitors and ARNIs for HF, examine how cost-effectiveness varies by ejection fraction (EF) and drug price, and estimate the effect of negotiated prices on cost-effectiveness.
Methods: A systematic literature search identified cost-effectiveness analyses of SGLT2 inhibitors and ARNIs versus standard of care for the treatment of HF from a US perspective, published through 2025. Analyses were stratified by HF with reduced EF (<40%, HFrEF), moderately reduced EF (40% to 49%, HFmrEF), and preserved EF (≥50%, HFpEF). Incremental cost-effectiveness ratios were estimated at negotiated drug prices from base-case, threshold, and sensitivity analyses of drug pricing. Key drivers of cost-effectiveness were identified from the top 3 variables in 1-way sensitivity analyses.
Results: Of 821 studies identified, 16 were included: 11 HFrEF, 2 HFrEF/HFmrEF/HFpEF, and 3 HFmrEF/HFpEF. Across all EF categories, incremental cost-effectiveness ratios (2024 US dollars) versus standard of care ranged from $59 600 to $187 100/quality-adjusted life year (QALY) gained with SGLT2 inhibitors, $24 400 to $92 300 with ARNIs, and $69 300 to $91 500 with SGLT2 inhibitors + ARNIs. Incremental cost-effectiveness ratios in studies of…
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