Heart failure & cardiomyopathies
Pharmacologic Treatment of Heart Failure With Reduced Ejection Fraction: An Updated Systematic Review and 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
Methodological detailsfrequentist network meta-analysis
- Frequentist network meta-analysis
Pooled result
As reported in the abstract
All-cause mortality
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
| Outcome | Additional life-years (life-years) (95% CI) |
|---|---|
| Life-years gained vs no treatment (representative 70-year-old patient) — Quadruple therapy vs No treatment | 5.3 (2.8–7.7) |
| Life-years gained vs no treatment (representative 70-year-old patient) — Quintuple therapy vs No treatment | 6.0 (3.7–8.4) |
Original publication
Pharmacologic Treatment of Heart Failure With Reduced Ejection Fraction: An Updated Systematic Review and Network Meta-Analysis. J Am Coll Cardiol. Published 30 August 2025. doi:10.
Summarised from the published abstract; every number is checked against it