Heart failure & cardiomyopathies
Efficacy of ARNIs on hard renal outcomes in heart failure with and without chronic kidney disease: when endpoint definition matters—an updated meta-analysis
Pooled result · Sustained 50% eGFR declineResult — go to the resultRelative risk 0.68 95% CI 0.57–0.82Authors' conclusion
The renal signal associated with Sac/Val in HF appeared at least partly dependent on endpoint definition. Composite kidney outcomes may best capture its potential nephroprotective effect, with sustained 50% eGFR decline showing a consistent pattern, whereas isolated ESKD remains inconclusive. These findings support a potential nephroprotective role of ARNIs but future research are needed.
Study context
- Population
- Adults with heart failure (HF) in randomized controlled trials (RCTs) and observational comparative studies comparing Sac/Val with angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or standard care13 study-level reports
- Participants
- 34,969 adults
- Comparison
- Sac/Val with angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or standard care
- Outcome
- Sustained 50% estimated glomerular filtration rate (eGFR) decline
Methodological detailsPRISMA 2020, random-effects meta-analysis, Hartung-Knapp and RCT-only sensitivity analyses, hierarchical cross-endpoint approach
- PRISMA 2020
- Random-effects meta-analysis
- Hartung-Knapp and RCT-only sensitivity analyses
- Hierarchical cross-endpoint approach
Pooled result
As reported in the abstract
Relative risk
0.68
95% CI 0.57–0.82
Sac/Valvs angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or standard care
RR 0.68 (95% CI 0.57–0.82)
Further pooled results
| Outcome | RR (95% CI) | |
|---|---|---|
| Composite kidney outcomeLower risk with Sac/Val | 0.70 (0.58–0.84) | |
| ESKDDirectionally favourable but not statistically significant | 0.80 (0.64–1.00) | |
| 0.512Relative risk (log scale) |
| Outcome | MD (mL/min/1.73 m²/year) (95% CI) | |
|---|---|---|
| Annualized eGFR declineSlower annualized eGFR decline with Sac/Val | 0.52 (0.35–0.69) | |
| −0.500.51Difference, mL/min/1.73 m²/year (linear scale) |
- Composite kidney outcome: most robust and consistent signal, including in RCT-only analyses
Original publication
Efficacy of ARNIs on hard renal outcomes in heart failure with and without chronic kidney disease: when endpoint definition matters—an updated meta-analysis. ESC Heart Fail. Published 5 June 2026. doi:10.
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