Sacubitril/valsartan in patients with heart failure with reduced ejection fraction with end-stage of renal disease

Abstract

Aims: Sacubitril/valsartan (SV) reduced heart failure hospitalization and cardiovascular mortality compared with enalapril in the Prospective Comparison of ARNI with ACE-I to Determine Impact on Global Mortality and Morbidity in Heart Failure trial. However, this trial excluded patients with end stage of renal disease (ESRD); thus, the efficacy and safety of SV in heart failure with reduced ejection fraction (HFrEF) with ESRD remains uncertain.

Methods and results: We retrospectively analysed the clinical and laboratory data of 501 HFrEF patients who administered with SV from March 2017 to April 2019 in a single tertiary university hospital. A total of 23 HFrEF patients with ESRD on dialysis [58.3% non-ischaemic heart failure; left ventricular ejection fraction (LVEF): 29.7 ± 4.4%] were included in this study. At baseline and follow-up visit, we evaluated cardiovascular biomarkers such as high-sensitive troponin T (hsTnT), soluble ST2 (sST2), echocardiographic parameters, and clinical and adverse events. The mean dose of SV was 90 ± 43 mg/day at baseline and 123 ± 62 mg/day at last follow-up (follow-up duration: median 132 days). The level of hsTnT was significantly reduced from 236.2 ± 355.3 to 97.0 ± 14.0 pg/mL (P = 0.002), and the sST2 level was significantly reduced from 40.4 ± 44.0 to 19.6 ± 14.1 ng/mL (P = 0.005). LVEF was significantly improved from 29.7 ± 4.4% to 40.8 ± 10.4% (P = 0.002). During the follow-up, up-titration, down-titration, and maintenance of SV dosing were observed in 7 (30%), 5 (21.7%), and 11 patients (47.8%), respectively. SV down-titration group had adverse events including symptomatic hypotension (systolic blood pressure <100 mmHg) (n = 4) and dizziness (n = 1), but they did not discontinue SV therapy.

Conclusions: We found that SV could safely reduce the hsTnT and sST2 levels and improve LVEF in HFrEF patients with ESRD. As far as we know, this is the first study to show the efficacy and safety of SV in HFrEF with ESRD on dialysis. Larger prospective, long-term follow-up study should be warranted.

Keywords: Dialysis; End-stage renal disease; Heart failure with reduced ejection fraction patients; Sacubitril/valsartan.