At ESC Congress 2025, results of a systematic review and meta-analysis were presented evaluating sacubitril/valsartan in heart failure with reduced ejection fraction (HFrEF) among patients with an estimated glomerular filtration rate (eGFR) below 30 ml/min/1.73 m².

The analysis included 9,464 patients from 10 studies, of which 2 were randomized controlled trials. Average age was 65 years, and follow-up ranged from 6 to 27 months. Compared with standard therapy, sacubitril/valsartan reduced mortality and hospitalizations by 41% (risk ratio [RR] 0.59; 95% confidence interval [CI] 0.36–0.96; p<0.01). However, effects on broader cardiovascular outcomes were inconclusive (RR 0.84; 95% CI 0.54–1.30). Importantly, treatment was not associated with a higher rate of adverse events.

These findings provide evidence that sacubitril/valsartan offers clinical benefit in patients with HFrEF and severe kidney dysfunction. Nevertheless, dedicated large-scale randomized trials remain necessary to establish safety and confirm these results.