Initiating combination pharmacotherapy early may offer economic value in heart failure with reduced ejection fraction (HFrEF). A modelling analysis published in Heart evaluated the cost-effectiveness of five first-line pharmacotherapy strategies for HFrEF from the perspective of the National Health Service (NHS) England.

A lifetime cohort Markov model compared five treatment combinations: angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) with beta-blocker (BB); ACEI/ARB + BB + mineralocorticoid receptor antagonist (MRA); angiotensin receptor–neprilysin inhibitor (ARNI) + BB + MRA; ACEI/ARB + BB + MRA + sodium–glucose cotransporter-2 inhibitor (SGLT2i); and ARNI + BB + MRA + SGLT2i. Baseline hospitalization and mortality rates were derived from real-world data, while treatment effects were informed by hazard ratios from randomized trials.

Among individuals able to tolerate ACEI, ACEI + BB + MRA + SGLT2i was the most cost-effective regimen (£12,124; 5.72 quality-adjusted life years [QALYs]; incremental cost-effectiveness ratio [ICER] £7,699). For ACEI-intolerant individuals, ARNI + BB + MRA + SGLT2i showed the greatest cost-effectiveness (£18,950; 6.04 QALYs; ICER £15,821), followed by ARB + BB + MRA + SGLT2i (£11,842; 5.59 QALYs).

Overall, first-line quadruple pharmacotherapy demonstrated favorable cost-effectiveness compared with stepwise treatment approaches in HFrEF.