Guideline-directed medical therapies (GDMTs) for heart failure (HF) have evolved with the addition of sodium-glucose cotransporter-2 inhibitors (SGLT2i) and angiotensin receptor-neprilysin inhibitors (ARNI), although their economic value across settings remains uncertain.

A systematic review and meta-analysis published in Value in Health evaluated the incremental net benefit (INB) of SGLT2i and/or ARNI added to conventional GDMT. The analysis included 70 studies and stratified results by HF phenotype, country income level, and analytic perspective.
Adding SGLT2i to GDMT was cost-effective for HF with reduced ejection fraction (HFrEF) in high-income countries from a healthcare perspective (pooled INB US$13,114.52; 95% CI 4,257.40-21,971.63). Evidence for upper-middle and lower-income countries was inconclusive.

A combined regimen of SGLT2i and ARNI appeared cost-effective in high- and upper-middle-income settings, although evidence was limited. Replacing other renin–angiotensin–aldosterone system blockers with ARNI was cost-effective only for HFrEF from a societal perspective in high-income countries (INB US$14,843.66; 95% CI 566.36-29,120.96). Evidence for other HF phenotypes remained inconclusive.

These findings indicate that cost-effectiveness varied by HF subtype and economic setting. Additional evidence is needed across broader populations and healthcare systems.