Effects of sacubitril/valsartan in patients with heart failure with reduced ejection fraction and an eGFR below 30 ml/min/1.73 m2

Sacubitril/valsartan is widely used in the treatment of heart failure with reduced ejection fraction (HFrEF), demonstrating benefits in reducing mortality and hospitalizations. However, its efficacy and safety in patients with an estimated glomerular filtration rate (eGFR) below 30 ml/min/1.73 m² remain uncertain. This systematic review and meta-analysis evaluate its impact on this population.

The aim was to perform a systematic review and meta-analysis of studies assessing mortality, cardiovascular events, left ventricular ejection fraction (LVEF), and hospitalization in patients with HFrEF and eGFR <30 ml/min/1.73 m² treated with sacubitril/valsartan versus standard therapy.

The study data were computed as risk ratio with a 95% confidence interval. Searches were conducted in PubMed, Embase, and Cochrane for randomized controlled trials (RCTs) and non-randomized studies in patients with HFrEF and eGFR <30 ml/min/1.73 m² who received sacubitril/valsartan or standard treatment. The data were pooled as risk ratio (RR) and confidence interval (CI) was assumed as 95%. Statistical analysis was performed using RStudio and RevMan, with heterogeneity assessed using I² statistics.

We included 9,464 patients from 10 studies (including 2 RCTs), all with HFrEF and eGFR <30 ml/min/1.73 m². Follow-up ranged from 6 to 27 months, with a mean age of 65.4 ± 3.8 years. Sacubitril/valsartan significantly reduced mortality by 41% (RR: 0.59, 95% CI: 0.36–0.96, p<0.01) and hospitalizations by 41% (RR: 0.59, 95% CI: 0.36–0.96, p<0.01). However, its effect on overall cardiovascular events was inconclusive (RR: 0.84, 95% CI: 0.54–1.30, p=0.12).

Our meta-analysis suggests that sacubitril/valsartan provides clinical benefits by reducing mortality and hospitalizations without a significant increase in adverse events in patients with HFrEF and eGFR <30 ml/min/1.73 m². Further high-quality randomized trials are needed to confirm these findings.

Mortality ARNI X Standard Treatment