Sacubitril/valsartan was associated with a lower risk of sustained 50% eGFR decline (RR 0.68; 95% CI 0.57-0.82) and composite kidney outcomes (RR 0.70; 95% CI 0.58-0.84) in heart failure.
Meta-Analysis (n=34,969)
Does sacubitril/valsartan reduce adverse renal outcomes compared to ACEi, ARB, or standard care in adults with heart failure?
Sacubitril/valsartan demonstrates a nephroprotective effect in heart failure patients when assessed by composite kidney outcomes or sustained eGFR decline, though the benefit for isolated end-stage kidney disease remains inconclusive.
Relative Risk: 0.68 (95% CI 0.57–0.82)
Abstract Background The renal effects of sacubitril/valsartan (Sac/Val) in heart failure (HF) remain incompletely defined, partly because kidney outcomes in pivotal HF trials have been variably prespecified and heterogeneously defined. We performed an updated systematic review and meta-analysis to assess whether the apparent renal signal of Sac/Val varies according to endpoint definition. Methods This updated systematic review was conducted in accordance with PRISMA 2020. Building on the pre-existing evidence base from prior meta-analyses, we performed an updated search of PubMed and Web of Science. Randomized controlled trials (RCTs) and observational comparative studies in adults with HF comparing Sac/Val with angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or standard care were included if renal outcome data were extractable. Renal outcomes were analyzed using a hierarchical cross-endpoint approach, including sustained ≥50% estimated glomerular filtration rate (eGFR) decline, end-stage kidney disease (ESKD), composite kidney outcomes, and annualized eGFR decline. Random-effects meta-analysis was performed, with Hartung-Knapp and RCT-only sensitivity analyses. Results Overall, 13 study-level reports comprising 34,969 patients were included. Sac/Val was associated with a lower risk of sustained 50% eGFR decline (RR 0.68, 95% CI 0.57–0.82) and composite kidney outcome (RR 0.70, 95% CI 0.58–0.84), with the composite endpoint showing the most robust and consistent signal, including in RCT-only analyses. By contrast, the association for ESKD alone was directionally favorable but not statistically significant (RR 0.80, 95% CI 0.64–1.00). Sac/Val was also associated with a slower annualized eGFR decline (MD 0.52 mL/min/1.73 m2/year, 95% CI 0.35–0.69). Conclusions 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.
Cianciolo et al. (Fri,) conducted a meta-analysis in Heart failure (n=34,969). Sacubitril/valsartan vs. Angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or standard care was evaluated on Sustained ≥50% eGFR decline (RR 0.68, 95% CI 0.57-0.82). Sacubitril/valsartan was associated with a lower risk of sustained 50% eGFR decline (RR 0.68; 95% CI 0.57-0.82) and composite kidney outcomes (RR 0.70; 95% CI 0.58-0.84) in heart failure.