Efficacy and safety of sacubitril/valsartan in the management of heart failure with reduced ejection fraction and chronic kidney disease: a systematic review and meta-analysis
B Chan Chin, C Chuah, J Y ChenAbstract
Background
Despite an improvement in survival rates in recent years with the introduction of sacubitril/valsartan, the prognosis of heart failure with reduced ejection fraction (HFrEF) remains poor. One negative prognostic factor is the presence of concomitant chronic kidney disease (CKD), a common comorbidity in patients with HFrEF. Advanced CKD not only limits optimisation of medical therapy, but also increases the risk of adverse events. The landmark PARADIGM-HF trial, which showed benefit of sacubitril/valsartan, excluded patients with chronic kidney disease stage 4 or above, hence there is an uncertainty regarding the use of this medication in patients with both HFrEF and advanced CKD.
Purpose
To study the efficacy and safety of sacubitril/valsartan in patients with concomitant HFrEF and advanced CKD
Methods
A systematic review of the literature available in PubMed, SCOPUS, Web of Science, Cochrane Library, ClinicalTrials.gov and the International Clinical Trials Registry was conducted, to find research studies reporting the use of sacubitril/valsartan in patients with concomitant HFrEF and CKD. Data extracted included study design, baseline characteristics of patients, left ventricular ejection fraction (LVEF), and estimated glomerular filtration rate (eGFR) at baseline and follow up, all-cause and cardiovascular mortality, heart failure hospitalisations, progression to end-stage kidney disease (ESKD) and adverse effects. A meta-analysis was performed, and effect estimates were calculated with the random effects model. Heterogeneity was mitigated with meta-regression and sensitivity analyses.
Results
Eight observational studies were included. There was a total of 5,216 patients, with a mean age of 66.8 ± 13.5 years, with 69.2% of patients being male. Baseline eGFR and LVEF are demonstrated in Figure 1. There was a significant improvement in LVEF by 10% in the sacubitril/valsartan group from baseline to follow up, and after sensitivity analysis adjusting for unequal group sizes, there was a reduction in heart failure hospitalisations (HFH) in the intervention group, compared to control (Figure 2). There was no definite improvement in renal function, and no difference in all-cause or cardiovascular mortality, progression to ESKD, and side effects such as hyperkalaemia and hypotension between the two groups. There was a substantial level of heterogeneity and variability between studies, likely due to selection bias, unbalanced group sizes and differences in intervention used in the control group.
Conclusion
This study found that in observational studies, sacubitril/valsartan significantly improved LVEF in patients with HFrEF and advanced CKD, and likely reduces heart failure hospitalisations. It suggests that sacubitril/valsartan could be safe to use in this cohort of patients. However, these findings should be interpreted with care due to substantial heterogeneity and risk of bias, and highlight the need for randomised controlled trials.Figure 1.Baseline characteristicsFor image description, please refer to the figure legend and surrounding text.Figure 2.Effect of sacubitril/valsartanFor image description, please refer to the figure legend and surrounding text.