Model-based cost-effectiveness analysis of first-line pharmacotherapy combinations in adults with chronic heart failure and reduced ejection fraction

BACKGROUND: Pharmacotherapy combinations have been shown to improve survival and reduce hospitalisations in adults with chronic heart failure with reduced ejection fraction (HFrEF); however, their cost-effectiveness when used as first-line treatment remains uncertain. METHODS: A lifetime cohort Markov model was developed from the perspective of the NHS in England to assess the cost-effectiveness of five first-line pharmacotherapy combinations: (i) angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) and beta-blocker (BB) (NICE-recommended treatment at the time of analysis); (ii) ACEI/ARB, BB and mineralocorticoid receptor antagonists (MRA); (iii) angiotensin receptor-neprilysin inhibitor (ARNI), BB and MRA; (iv) ACEI/ARB, BB, MRA and sodium-glucose cotransporter-2 inhibitor (SGLT2i); and (v) ARNI, BB, MRA and SGLT2i. Baseline hospitalisation and mortality rates were informed by real-world data, while treatment effects (HRs) were derived from a review of randomised controlled trials. RESULTS: Among individuals able to tolerate an ACEI, the combination of ACEI, BB, MRA and SGLT2i (cost, £12 124; quality-adjusted life years (QALYs), 5.72) was found to be the most cost-effective first-line treatment option with an incremental cost-effectiveness ratio (ICER) of £7699.Among individuals unable to tolerate an ACEI, the combination of ARNI, BB, MRA and SGLT2i (cost, £18 950; QALYs, 6.04) was found to be the most cost-effective first-line treatment option with an ICER of £15 821. The next most cost-effective first-line treatment option was the combination of ARB, BB, MRA and SGLT2i (cost, £11 842; QALYs, 5.59). These findings were primarily driven by the greater relative QALY gain of ARNI compared with ARB. CONCLUSIONS: This study demonstrates that a first-line quadruple pharmacotherapy combination is cost-effective compared with a stepwise approach for treating people with HFrEF, suggesting that wider adoption of early initiation of quadruple pharmacotherapy may improve health outcomes and optimise healthcare resource use.