Tongpoonsakdi N.Tansawet A.Yingchoncharoen T.Amornritvanich P.Noviyani R.Thavorncharoensap M.McKay G.J.Attia J.Thakkinstian A.Mahidol University2026-05-132026-05-132026-01-01Value in Health (2026)10983015https://repository.li.mahidol.ac.th/handle/123456789/116705Background: Guideline-directed medical therapies (GDMTs) have improved heart failure (HF) outcomes, particularly with the emergence of sodium-glucose cotransporter-2 inhibitors (SGLT2i) and angiotensin receptor-neprilysin inhibitors (ARNI). However, their cost-effectiveness remains uncertain across HF phenotypes, income levels, and analytic perspectives. Objectives: The study aimed to evaluate and compare the incremental net benefit (INB) of SGLT2i and/or ARNI added to traditional GDMTs, stratified by HF phenotype, country income level, and study perspective. Methods: PubMed, Scopus, and the Cost-Effectiveness Analysis Registry were searched through October 2024. Economic evaluations assessing SGLT2i or ARNI added to traditional GDMTs were included. INBs and variances were extracted or calculated; if unavailable, variances were imputed via regression or based on similar studies. Random-effects meta-analyses were performed by treatment-comparator pairs, HF phenotype, income level, and perspective. Risk of bias was assessed using the Bias in Economic Evaluation checklist. Results: Seventy studies were included. Adding SGLT2i to traditional GDMTs was cost-effective in high-income countries (HICs) for HF with reduced ejection fraction (HFrEF) from healthcare perspective (pooled INB = US $13 114.52; 95% CI: 4257.40–21 971.63), whereas evidence was inconclusive for upper-middle (UMICs) or lower-income countries. Quadruple regimen (SGLT2i + ARNI) appeared cost-effective in HICs and UMICs, although evidence was limited. Replacing other renin-angiotensin-aldosterone system blockers with ARNI was only cost-effective for HFrEF from societal perspective in HICs (INB = US $14 843.66; 95% CI: 566.36–29 120.96). Evidence for other HF phenotypes remained inconclusive evidence. Conclusions: Adding SGLT2i and ARNI improves GDMTs cost-effectiveness for the treatment of HFrEF, especially in HICs. More evidence is needed for other HF types and income settings.MedicineReviewSCOPUS10.1016/j.jval.2026.03.22332-s2.0-1050379491161524473341962835