Heart failure & cardiomyopathiesMeta-analysis

Pharmacologic Treatment of Heart Failure With Reduced Ejection Fraction

J Am Coll CardiolPublished

  • Systematic review and network meta-analysis of randomised trials
  • frequentist network meta-analysis

Authors' conclusion

This analysis reinforces the substantial mortality and morbidity benefit associated with the currently recommended quadruple therapy regimen (ARNi, β-blockers, MRAs, and SGLT2i) in patients with HFrEF.

Study context

Population
Patients with heart failure with reduced ejection fraction (HFrEF) (randomized controlled trials (RCTs) through April 2025)
Participants
103,754 patients · 89 RCTs
Comparison
Pharmacotherapy regimens vs placebo
Outcome
All-cause mortality

Pooled result

As reported in the abstract

Each group vs placeboHazard ratio (95% CI)
Quintuple therapy
0.35(0.27–0.45)
Quadruple therapy
0.39(0.32–0.49)

Further pooled results

Outcomeadditional life-years (life-years) (95% CI)
Life-years gained vs no treatment (representative 70-year-old patient) — Quadruple therapy vs No treatment5.3 (2.8–7.7)
Life-years gained vs no treatment (representative 70-year-old patient) — Quintuple therapy vs No treatment6.0 (3.7–8.4)

Original publication

Pharmacologic Treatment of Heart Failure With Reduced Ejection Fraction. J Am Coll Cardiol. Published 30 August 2025. doi:10.1016/j.jacc.2025.08.054

Summarised from the published abstract; every number is checked against it