scholarly journals Renal protective effect of sacubitril/valsartan in patients with heart failure

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hui-Ling Hsieh ◽  
Chun-You Chen ◽  
Cheng-Hsien Chen ◽  
Shih-Chang Hsu ◽  
Wen-Cheng Huang ◽  
...  

AbstractSacubitril/valsartan is a combined neprilysin inhibitor/angiotensin II receptor blocker designed for treatment of heart failure (HF). Nonetheless, its renal protective effect remained an issue of debate. This retrospective cohort study investigated the renal protective effect of sacubitril/valsartan in HF patients. HF patients on sacubitril/valsartan or valsartan for > 30 days were matched for gender, age, estimated glomerular filtration rate (eGFR), and left ventricular ejection fraction (LVEF) to be enrolled into analysis. The follow-up period was 18 months. The outcomes included end eGFR, renal function decline defined as 20% reduction of eGFR, mortality, and HF-related hospitalization. Each group had 137 patients after matching. The mean age was 72.7 years and 65.7% were male. Mean eGFR was 70.9 mL/min/1.73 m2 and LVEF was 54.0% at baseline. Overall, the eGFR of sacubitril/valsartan groups was significantly higher than valsartan group at the end (P < 0.01). Subgroup analysis showed that the difference in eGFR was significant in subgroups with LVEF ≥ 40% or eGFR ≥ 60 mL/min/1.73 m2. Multivariate Cox regression model showed that sacubitril/valsartan group had significantly reduced risk for renal function decline (hazard ratio: 0.5, 95% confidence interval: 0.3–0.9). Kaplan–Meier curve showed no difference in the risk for cardiovascular mortality, all-cause mortality or HF-related hospitalization. We showed renal protective effect of neprilysin inhibition in HF patients and specified that subgroups with LVEF ≥ 40% or eGFR ≥ 60 mL/min/1.73 m2 were sensitive to this effect, suggesting an optimal subgroup of this treatment.

Angiology ◽  
2021 ◽  
pp. 000331972110473
Author(s):  
Umut Karabulut ◽  
Kudret Keskin ◽  
Dilay Karabulut ◽  
Ece Yiğit ◽  
Zerrin Yiğit

The angiotensin receptor–neprilysin inhibitor (ARNI) sacubitril/valsartan and sodium-glucose cotransporter-2 (SGLT-2) inhibitor dapagliflozin have been shown to reduce rehospitalization and cardiac mortality in patients with heart failure (HF) with reduced ejection fraction (HFrEF). We aimed to compare the long-term cardiac and all-cause mortality of ARNI and dapagliflozin combination therapy against ARNI monotherapy in patients with HFrEF. This retrospective study involved 244 patients with HF with New York Heart Association (NYHA) class II–IV symptoms and ejection fraction ≤40%. The patients were divided into 2 groups: ARNI monotherapy and ARNI+dapagliflozin. Median follow-up was 2.5 (.16–3.72) years. One hundred and seventy-five (71.7%) patients were male, and the mean age was 65.9 (SD, 10.2) years. Long-term cardiac mortality rates were significantly lower in the ARNI+dapagliflozin group (7.4%) than in the ARNI monotherapy group (19.5%) ( P = .01). Dapagliflozin [Hazard Ratio (HR) [95% Confidence Interval (CI)] = .29 [.10–.77]; P = .014] and left ventricular ejection fraction (LVEF) [HR (95% CI) = .89 (.85–.93); P < .001] were found to be independent predictors of cardiac mortality. Our study showed a significant reduction in cardiac mortality with ARNI and dapagliflozin combination therapy compared with ARNI monotherapy.


Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Yu Chiang Wang ◽  
Alberto Pinsino ◽  
Lorenzo Braghieri ◽  
Li Pang ◽  
Matteo Fabbri ◽  
...  

Introduction: Serum creatinine (sCr) is routinely used to calculate estimated glomerular filtration rate (eGFR) in heart failure (HF) pts. However, changes in muscle mass may limit the accuracy of sCr as marker of renal function in this population. Cystatin C (CysC) is independent of muscle mass and provides an alternative measure of eGFR. In prior studies, higher sCr/CysC ratio has been associated with higher muscle mass. Herein, we compared CysC- and sCr-based eGFR at serial time points among pts admitted with HF. We hypothesized that muscle mass would decline during HF admission and this would result in a decrease of sCr/CysC ratio. Methods: We pooled pts from 3 trials performed in pts admitted with HF (DOSE, ROSE and CARRESS-HF). eGFR was calculated using CKD-EPI-CysC equation (eGFRCysC) and sCr-based MDRD equation (eGFRsCr). The relative difference between eGFRCysC and eGFRsCr (ΔeGFR) was calculated as follows: (eGFRCysC-eGFRsCr)/ eGFRsCr. To control for confounders, we analyzed changes in sCr/CysC ratio and in ΔeGFR among pts with samples available at both admission and a subsequent time point. Results: A total of 2849 samples were available in 841 pts (age 68 ± 13, 26% female, left ventricular ejection fraction 36 ± 17%). Compared with eGFRsCr, eGFRCysC reclassified 50% of the samples to different GFR categories, mainly to more advanced renal dysfunction (Fig. A). eGFRCysC was significantly lower than eGFRsCr at all time points (Fig. B). From time of admission to all subsequent time points, sCr/CysC ratio declined while ΔeGFR widened (all p-values<0.001). At time of enrollment in CARRESS-HF, each additional day of HF admission was associated with a decline in sCr/CysC ratio of 1.5% (p=0.04). Conclusions: The use of CysC reclassifies a large proportion of pts admitted with HF to more advanced renal dysfunction when compared to sCr-based assessment. The discrepancy between CysC- and sCr-based eGFR appears to widen during HF admission, likely due to muscle mass wasting.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
Y S Suematsu ◽  
A I Ideishi ◽  
K T Tashiro ◽  
T K Kuwano ◽  
S M Miura

Abstract Introduction Angiotensin receptor-neprilysin inhibitor (ARNI) increases natriuretic peptide and improves heart failure. We previously reported that ARNI has the effects of suppression of myocardial hypertrophy and fibrosis in addition to reduction of afterload by natriuretic effect. We investigated the effects of ARNI against mice model of atherosclerosis and heart failure. Method and results Apolipoprotein E knockout mice fed high cholesterol diet for 4 weeks were divided into four groups: no treatment (CTL), valsartan 30 mg/kg (VAL), sacubitril (neprilysin inhibitor) 30 mg/kg (SAC), and ARNI 60mg/kg for additional 13 weeks. Body weight and systolic blood pressure in the VAL, SAC and ARNI groups did not show significant differences compared to those in the CTL group. Serum brain natriuretic peptide (BNP) in ARNI group (605±221 pg/ml) was significantly increased than that in VAL (391±57 pg/ml) and SAC (357±91 pg/ml) groups, but not CTL group (393±192 pg/ml). Although the rate of atherosclerotic area in aorta was 16.3±5.8% after treatment, there were no significant differences between the groups. In the CTL group, left ventricular ejection fraction (LVEF, 81.6±4.8%) and fractional shortening (FS, 44.8±5.8%) at baseline were significantly reduced after treatment (67.8±8.2% and 33.3±6.1%). Interestingly, LVEF (76.6±6.7%) and FS (40.1±6.1%) after treatment in the ARNI group were significantly preserved compared to those in the CTL group. In real time polymerase chain reaction analysis of LV after treatment, relative mRNA expression of BNP and angiogenetic factors including ATPase sarcoplasmic/endoplasmic reticulum Ca transporting 2, vascular endothelial growth factor A, cluster of differentiation 34 in ARNI group were significantly increased than those in the CTL group. Transforming growth factor-β in ARNI group was significantly reduced than that in the CTL group. Conclusion Although ARNI did not suppress atherosclerosis in mice, it preserved LVEF via improving angiogenetic ability.


2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Sha Fu ◽  
Zhenjian Xu ◽  
Baojuan Lin ◽  
Junzhe Chen ◽  
Qiuyan Huang ◽  
...  

Abstract Background and Aims Angiotensin receptor–neprilysin inhibitor (ARNI) sacubitril–valsartan is a landmark drug in heart failure with reduced ejection fraction (HFrEF), however, it remains unclear in patients with heart failure with preserved ejection fraction (HFpEF), especially the data of ARNI treatment on peritoneal dialysis (PD) patients with HFpEF are lacking. The present study was designed to determine the efficacy and safety of sacubitril–valsartan in patients with HFpEF undergoing peritoneal dialysis. Method We assigned end stage renal disease (ESRD)patients, receiving peritoneal dialysis for 3 months, with New York Heart Association (NYHA) class II to IV heart failure, left ventricular ejection fraction ≥ 50%, and elevated level of N-terminal pro–B-type natriuretic peptide (NT-proBNP) to receive sacubitril/valsartan treatment. Patients were regularly followed up after medication treatment. Wilcoxon matched-pair signed-rank (2 samples) tests were applied to investigate the alterations in Clinical and biochemical parameters as the efficacy before and after taking sacubitril–valsartan, and safety was also assessed. Results Twenty-one patients were recruited in this study. Compared with baseline levels, NT-proBNP levels (p=0.002) and heart rate (p=0.031) were markedly decreased after treatment with sacubitril/valsartan, signs and symptoms of heart failure (21/21 versus 15/21, p=0.021) and NYHA classification were notably improved after 3-12 months follow-up. Conclusion The present data suggested that sacubitril/valsartan treatment in the patients with HFpEF undergoing peritoneal dialysis was effective and safe, which is the first study about sacubitril/valsartan treatment for the PD patients with HFpEF, and it may bring the hope for these patients due to no other effective methods at present.


Cardiology ◽  
2017 ◽  
Vol 137 (2) ◽  
pp. 96-99 ◽  
Author(s):  
Henrik Fox ◽  
Thomas Bitter ◽  
Dieter Horstkotte ◽  
Olaf Oldenburg

Sleep-disordered breathing (SDB) is highly prevalent in patients with heart failure (HF), and is known to be associated with a worse prognosis. The severity of central sleep apnea is thought to mirror cardiac dysfunction. The novel angiotensin receptor-neprilysin inhibitor (ARNi) sacubitril has been shown to improve HF, but a relationship between treatment with ARNi and the severity of SDB has not yet been investigated. We report the case of a 71-year-old male with HF and SDB. Treatment with sacubitril/valsartan was associated with improved cardiac function, as shown by a reduction in the level of N-terminal prohormone of brain natriuretic peptide from 3,249 to 1,720 pg/mL, and an improvement in left-ventricular ejection fraction from 30 to 35%. This was accompanied by a marked reduction in the apnea-hypopnea index (from 41 to 19/h). To the best of our knowledge, this is the first case to document parallel improvements in HF and SDB after the initiation of ARNi treatment.


2017 ◽  
Vol 10 (1) ◽  
pp. 24
Author(s):  
Dyah Siswanti E ◽  
Fatmawati Fatmawati ◽  
M. Ikhsanul Fikri

Worsening renal function in patient with congestive heart failure affect the length of hospital stay. The purpose of thisstudy was to describe the creatinine serum levels and the length of hospital stay in patient with congestive heartfailure treated in Arifin Achmad hospital Riau Province January 2012 – December 2014. This study was done withcross sectional approach. This study found the most common creatinine serum levels found were <1.5 mg/dl (73.2%)with an average of 1.30 mg/dl and the range was 0.10 – 6.63 mg/dl. The value of left ventricular ejection fraction withan average of 44.9% and the range was 12% - 79%. Length of hospital stay in patients were >5 days commonly withan average of 7.29 days and the range was 1 – 29 days. The result of this study showed that the possibility ofcreatinine serum levels is not the only one predictor to determine the length of hospital stay in patient with congestiveheart failure.


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