(VP002) A COST-UTILITY ANALYSIS OF HEART FAILURE REDUCED EJECTION FRACTION SEQUENCING STRATEGIES

Background: Heart failure with reduced ejection fraction (HFrEF) guidelines recommend quadruple therapy with an angiotensin-receptor blocker/neprilysin inhibitor (ARNI), a beta-blocker (BB), a mineralocorticoid receptor agonist (MRA), and a sodium–glucose cotransporter-2 inhibitor (SGLT2I). A scoping of methods of initiating and titrating HFrEF quadruple therapy, known as sequencing strategy, revealed 3 themes and 6 sequencing profiles distinguished by number and type of medication first initiated and relationship between initiation and titration. The aim of this study was to compare the cost-utility of these sequencing profiles for HFrEF quadruple therapy.

METHODS AND RESULTS: We performed a cost-utility analysis using an individual-based state-transition microsimulation model including six sequencing profiles: Profile 1 (traditional), Profile 2 (one initial medication), Profile 3 (two initial medications: SGLT2I and BB), Profile 4 (two initial medications: ARNI and BB), Profile 5 (three initial medications), and Profile 6 (four initial medications), each modeled in two versions with adjustment frequency of every fortnight (version a) or every week (version b). The primary outcomes were QALYs and NMB with a willingness-to-pay threshold of $50,000 and a primary analysis of 10,000 individuals over their lifetime. We conducted probabilistic sensitivity analyses with 1,000 samples and 10,000 trials, 1-way sensitivity analyses, and two scenario analyses (scenario 1 – medication adjustment ends after 3 months, scenario 2 - ).

The range of QALYs observed in the study was 8.88-9.06, with Profile 6b having the highest QALY. The range of NMBs was $363,177-$369,277 , with Profile 6a providing the highest NMB. Profile 1a resulted in both the lowest QALY and NMB. Profile 6a was also the most cost-effective strategy in 87.9% of the iterations, followed by Profile 4a (5.4%) and Profile 5a (5.3%). The NMB was most sensitive to changes in the discount rate and incidence rate of clinical outcomes. In scenario 1, where medication adjustment was stopped after 3 months, Profile 1a failed to achieve target dose of the quadruple therapy, resulting in significantly fewer QALYs and NMB. In scenario 2, assuming that sub-target doses were ineffective, faster medication adjustment profiles (version b) were more likely to be optimal.

Conclusion: The sequencing profile involving simultaneous initiation of HFrEF quadruple therapy (profile 6) resulted in the greatest QALYs and NMB, but the incremental benefit compared to other profiles was small. The key factor for optimizing outcomes was whether patients successfully attempted to achieve the target dose of all four medications regardless of the specific sequencing strategy employed.