Key result
Quadruple therapy with ARNI, BB, MRA, and SGLT2i reduced the risk of all-cause mortality compared to placebo and was the most cost-effective strategy for HFrEF.
Why the study?
To assess the cost-effectiveness of guideline-directed medical treatments for HFrEF using a network meta-analysis of randomized controlled trials feeding a decision tree-Markov model.
Does quadruple therapy with ARNI, BB, MRA, and SGLT2i improve survival and reduce hospitalizations in patients with HFrEF?
Meta-Analysis (n=75,978)
Does quadruple therapy with ARNI, BB, MRA, and SGLT2i improve survival and reduce hospitalizations in patients with HFrEF?
Quadruple therapy with ARNI, beta-blocker, MRA, and SGLT2 inhibitor is the most effective and cost-effective pharmacological strategy for HFrEF.
Answers are grounded in this paper and cite their sources.
Quadruple therapy warrants first-line use in eligible HFrEF patients; confirms and extends 2021 ESC guidelines with cost-effectiveness across systems.
Background and Aims To assess the cost-effectiveness of guideline-directed medical treatments for heart failure with reduced ejection fraction (HFrEF) by performing a network meta-analysis (NMA) of randomized controlled trials (RCTs) feeding a subsequent cost-effectiveness analysis. Methods A random-effects NMA of RCTs was conducted. The primary analysis included only RCTs evaluating drugs in the clinical settings as recommended in the 2021 European Society of Cardiology HF guidelines. Main efficacy outcomes included all-cause mortality (ACM) and total HF hospitalizations (HFH). A decision tree-Markov model was populated with NMA-derived efficacy estimates, quality-of-life data, and costs from United Kingdom (UK, main analysis), as well as Sweden and United States (US) (scenario analyses) healthcare perspectives. Results 47 RCTs (75,978 patients) were included. The risk of ACM and total HFH decreased with increasing number of pharmacological treatments. In the main (UK) analysis, the greatest benefit was observed with a quadruple therapy including angiotensin receptor–neprilysin inhibitor (ARNI) + β-blocker (BB) + mineralocorticoid receptor antagonist (MRA) + sodium–glucose cotransporter 2 inhibitors (SGLT2i), which resulted as the most cost-effective strategy (12.31 quality-adjusted life-years; net monetary benefit of £338,460; UK perspective). Findings were consistent in Sweden and US. Conclusion Quadruple therapy with ARNI+BB+MRA+SGLT2i had the highest probability of being the most cost-effective strategy. Our findings might inform future health economic policies and reimbursement decisions, while also considering affordability, budget impact, and implementation feasibility.
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Laborante et al. (2026) conducted a meta-analysis in Heart failure with reduced ejection fraction (HFrEF) (n=75,978). Quadruple therapy with ARNI, BB, MRA, and SGLT2i vs. Placebo was evaluated on All-cause mortality (IRR 0.48, 95% CI 0.34-0.69). Quadruple therapy with ARNI, BB, MRA, and SGLT2i reduced the risk of all-cause mortality compared to placebo and was the most cost-effective strategy for HFrEF.
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