A cost-effectiveness analysis of increased quadruple therapy use in heart failure with reduced ejection fraction in Singapore

BackgroundQuadruple therapy, comprising an angiotensin receptor-neprilysin inhibitor (ARNI), {beta}-blocker, mineralocorticoid receptor antagonist (MRA), and sodium-glucose cotransporter 2 inhibitor (SGLT2i), is guideline-recommended for heart failure with reduced ejection fraction (HFrEF). However, uptake in Singapore remains low. This study evaluated the cost-effectiveness of scaling up quadruple therapy from the current 30% uptake to realistic (80%) and stretch (100%) targets. MethodsWe developed a decision-analytic model combining a decision tree and Markov structure to simulate clinical and economic outcomes over a 10-year horizon from the Singapore healthcare system perspective. Transition probabilities were estimated using local real-world data for current regimens, and published literature for quadruple therapy. Costs were derived from hospital billing data and drug utilisation patterns. A probabilistic sensitivity analysis (1,000 simulations) assessed uncertainty. The willingness-to-pay (WTP) threshold was S$45,000 per quality-adjusted life year (QALY) gained. ResultsBoth scale-up scenarios were cost-effective. Compared to current practice, the 80% uptake scenario resulted in an incremental cost of S$2.57M and 110 additional QALYs (ICER: S$23,392/QALY) for 1000 patients over 10 years, while the 100% uptake scenario yielded 137 QALYs at an incremental cost of S$2.88M (ICER: S$21,117/QALY). Under conservative assumptions, both scenarios remained cost-effective. The probability of being cost-effective was 92% (80% uptake) and 96% (100% uptake). InterpretationScaling up quadruple therapy for HFrEF in Singapore is highly cost-effective. Implementation strategies to close the treatment gap should be prioritised to improve outcomes and maximise value in heart failure care.