A NETwork meta-analysis with COST-effectiveness evaluation of pharmacological treatments for heart failure with reduced ejection fraction: NET-COST-HFrEF.

In 30 seconds

This network meta-analysis of 47 randomized controlled trials involving 75,978 patients with heart failure with reduced ejection fraction assessed guideline-directed drug combinations and their cost-effectiveness. A decision tree–Markov model used efficacy estimates from the meta-analysis, with the United Kingdom as the main economic perspective and Sweden and the United States as scenario analyses. The combination of an angiotensin receptor–neprilysin inhibitor, β-blocker, mineralocorticoid receptor antagonist, and sodium-glucose cotransporter 2 inhibitor had the greatest modeled benefit and was the most cost-effective strategy in the UK analysis, yielding 12.31 quality-adjusted life-years and a net monetary benefit of £338 460.

Key findings

• Across the included trials, risks of all-cause mortality and total heart failure hospitalizations decreased as the number of pharmacological treatments increased.
• In the UK analysis, quadruple therapy produced 12.31 quality-adjusted life-years and a net monetary benefit of £338 460.
• Quadruple therapy had the highest probability of being the most cost-effective strategy; findings were consistent in Sweden and the United States.

Why it matters

The analysis compares both clinical outcomes and modeled economic value across combinations of guideline-directed therapies. Its findings suggest that the four-drug combination may offer the strongest value among the strategies assessed, while highlighting that cost-effectiveness evidence can inform health-economic and reimbursement decisions alongside considerations of affordability, budget impact, and implementation feasibility.

What to keep in mind

Cost-effectiveness estimates depend on a decision tree–Markov model and country-specific costs and perspectives; the UK was the main analysis, with Sweden and the United States assessed in scenario analyses.