LCZ696 and preservation of renal function in heart failure: A meta-analysis of 6 randomized trials

Chen, Xiaogen; Jin, Chunlei; Xie, Lan; Xiang, Meixiang

doi:10.31083/j.rcm.2020.01.2

Cited by 10 publications

(2 citation statements)

References 15 publications

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“…Interestingly, we found in our prior study that attenuation of renal medullary fibrosis, proteinuria, and protein cast formation were largely driven by the combination of sacubitril with the angiotensin receptor blocker (ARB) valsartan, as opposed to sacubitril alone. This is in line with other studies, where it has been demonstrated that valsartan is able to partially attenuate fibrosis in diabetic nephropathy [ 63 ] and alleviate renal injury in CVD patients [ 64 ]. Also notable from our prior study was the reduction in systolic BP in both sacubitril/valsartan and valsartan only groups, which contrasts with the trend for the increase demonstrated by sacubitril only dosage in this study.…”

Section: Discussionsupporting

confidence: 92%

Inhibition of neprilysin with sacubitril without RAS blockage aggravates renal disease in Dahl SS rats

et al. 2021

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Salt-sensitive (SS) hypertension is accompanied with severe cardiorenal complications. In this condition, elevated blood pressure (BP) resulting from salt retention is associated with counterintuitively lower levels of atrial natriuretic peptide (ANP). In plasma, ANP is degraded by the neprilysin; therefore, pharmacological inhibition of this metalloprotease (i.e., with sacubitril) can be employed to increase ANP level. We have shown earlier that sacubitril in combination with valsartan (75 lg/day each) had beneficial effects on renal function in Dahl SS rats. The goal of this study was to evaluate the effects of a higher dose of sacubitril on renal damage in this model. To induce hypertension, male Dahl SS rats were fed a 4% NaCl diet (HS) for 21 days, and were administered sacubitril (125 lg/day) or vehicle via s.c. osmotic pumps. At the end of the HS challenge, both groups exhibited similar outcomes for GFR, heart weight, plasma electrolytes, BUN, and creatinine. Sacubitril exacerbated kidney hypertrophy, but did not affect levels of renal fibrosis. We also observed aggravated glomerular lesions and increased formation of protein casts in the sacubitril-treated animals compared to controls. Thus, in Dahl SS rats, administration of sacubitril without renin-angiotensin-system blockage had adverse effects on renal disease progression, particularly in regards to glomerular damage and protein cast formation. We can speculate that while ANP levels are increased because of neprilysin inhibition, there are off-target effects of sacubitril, which are detrimental to renal function in the SS hypertensive state.

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Section: Discussionsupporting

confidence: 92%

Inhibition of neprilysin with sacubitril without RAS blockage aggravates renal disease in Dahl SS rats

et al. 2021

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“…Moreover, Kang et al [ 28 ] reported that LCZ696 significantly increased the estimated glomerular filtration rate ( P = .02) and reduced the NT-proBNP level ( P < .001) compared with irbesartan, valsartan, and enalapril. Another study by Chen et al [ 29 ] reported that LCZ696 was associated with a significantly reduced risk of renal function deterioration ( P = .02) compared with that of ACEI/ARB. Furthermore, NT-proBNP is related to the adverse outcomes of HF, and the reduction of NT-proBNP levels and nephrotoxicity are helpful in improving the survival of patients with HF.…”

Section: Discussionmentioning

confidence: 99%

The angiotensin receptor and neprilysin inhibitor, LCZ696, in heart failure: A meta-analysis of randomized controlled trials

Chen

Qian

et al. 2022

Medicine

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Background: LCZ696 is a novel neuroendocrine inhibitor that has been widely used in heart failure (HF). However, its advantage over other neuroendocrine inhibitors, such as angiotensin-converting enzyme inhibitors (ACEis) and angiotensin-receptor blockers (ARBs) has not been fully elucidated. This study aimed to provide the latest evidence regarding the efficacy and safety of LCZ696 as compared to other ACEis and ARBs with regards to the treatment of HF. Methods: We systematically searched databases, including PubMed, Embase, and the Cochrane Library, for relevant randomized controlled trials (RCTs). The outcome measures included all-cause mortality, rate of hospitalizations for HF, rate of death from cardiovascular causes, change in N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, and decline of renal function. Results: Five RCTs involving 19,078 patients were identified. The meta-analysis indicated that LCZ696 was associated with a significant reduction in all-cause mortality (hazard ratio [HR] = 0.84; 95% confidence interval [CI], 0.76–0.93; P = .0005), rate of hospitalizations for HF (HR = 0.80; 95% CI, 0.73–0.87; P < .00001), reduction in NT-proBNP levels (rate ratio = 0.78; 95% CI, 0.70–0.88; P < .0001), and decline in renal function (odds ratio = 0.77; 95% CI, 0.68–0.88; P < .0001) compared with ACEis and ARBs. However, there was no statistical difference in the rate of death from cardiovascular causes (HR = 0.86; 95% CI, 0.72–1.03; P = .09) between LCZ696 and ACEis and ARBs. Conclusion: LCZ696 is superior to ACEis and ARBs in the treatment of HF. Hence, it should be more widely used clinically.

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Sacubitril/valsartan improves cardiac function in Chinese patients with heart failure: a real‐world study

Chen

Liu

et al. 2021

ESC Heart Failure

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Aims Sacubitril/valsartan significantly reduced heart failure (HF) hospitalization and cardiovascular mortality in a randomized controlled trial. However, little is known about real-world efficacy and safety of sacubitril/valsartan in Chinese patients with HF with reduced ejection fraction (HFrEF). We aimed to evaluate whether sacubitril/valsartan could improve cardiac function in Chinese patients with HFrEF in a tertiary hospital in China. Methods and results Patients with HFrEF receiving sacubitril/valsartan in our hospital between January 2018 and January 2020 were recruited in the present study. We retrospectively collected and analysed all clinical parameters at baseline and during follow-up. A total of 100 consecutive patients (73% male) with HFrEF were recruited in the present study. During a median follow-up period of 365 days [interquartile range (IQR), 346-378], a pronounced improvement of cardiac function was achieved. New York Heart Association classification was significantly improved (P < 0.001), and median N-terminal pro-B-type natriuretic peptides level significantly decreased from 3003 pg/mL (IQR, 1513-5404) to 2039 pg/mL (IQR, 921-3955) (P = 0.010). Mean left ventricular ejection fraction increased from 31 ± 6% to 38 ± 10% (P < 0.001) and median left ventricular end-diastolic diameter reduced from 63 mm (IQR, 59-67) to 60 mm (IQR, 55-68) (P = 0.001). Mean pulmonary arterial systolic pressure decreased significantly from 49 ± 13 mmHg to 44 ± 12 mmHg (P < 0.001) and median right ventricular end-diastolic diameter reduced from 23 mm (IQR, 21-26) to 22 mm (IQR, 20-25) (P = 0.030). After treatment with sacubitril/valsartan, mean estimated glomerular filtration rate significantly decreased (from 88.8 ± 22.4 mL/min to 71.8 ± 27.3 mL/min, P < 0.001). Median serum creatinine and median blood urea nitrogen levels significantly increased [from 0.9 mg/dL (IQR, 0.8-1.0) to 1.1 mg/dL (IQR, 0.9-1.3), P < 0.001, and from 6.8 mmol/L (IQR, 5.5-8.9) to 8.0 mmol/L (IQR, 6.6-10.3), P = 0.002, respectively]. The proportion of patients with chronic kidney disease Stage 3/4 increased significantly from 8% to 39% (P < 0.001). Conclusions In Chinese patients with HFrEF, sacubitril/valsartan treatment was associated with a pronounced improvement of cardiac function, but might be prone to a decrease in blood pressure and deterioration in renal function.

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LCZ696 and preservation of renal function in heart failure: A meta-analysis of 6 randomized trials

Cited by 10 publications

References 15 publications

Inhibition of neprilysin with sacubitril without RAS blockage aggravates renal disease in Dahl SS rats

Inhibition of neprilysin with sacubitril without RAS blockage aggravates renal disease in Dahl SS rats

The angiotensin receptor and neprilysin inhibitor, LCZ696, in heart failure: A meta-analysis of randomized controlled trials

Sacubitril/valsartan improves cardiac function in Chinese patients with heart failure: a real‐world study

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