Acute Tubular Necrosis Associated with Angiotensin Receptor-Neprilysin Inhibitor

Background: The aim of this analysis was to examine the effect of the angiotensin receptor neprilysin inhibitor (ARNI) sacubitril/valsartan (LCZ696), compared with enalapril, on progressive worsening over time in patients with heart failure and reduced ejection fraction (HF-REF) enrolled in the Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidly in Heart Failure trial (PARADIGM-HF). Methods: In PARADIGM-HF, 4212 patients were randomized to enalapril and 4187 to sacubitril/valsartan. The primary outcome was the composite of cardiovascular (CV) death or hospitalization for heart failure (HF). To make a more comprehensive evaluation of HF worsening over time, we analysed the broader composite of CV death, HF hospitalization, emergency department visit for HF or intensification of therapy for HF (as time-to-first event) using the Kaplan-Meier (KM) method. Results: At baseline, 71% of patients were in NYHA functional class II and 24% in class III. Their mean LVEF was 27% and 93% were treated with a beta-blocker and 56% with a mineralocorticoid receptor antagonist. The median duration of follow-up was 27 months. The 1, 2 and 3 year KM rates for the composite outcome in the enalapril group were 16.5 (95% CI 15.5, 17.7)%, 27.6 (26.2, 29.1) and 34.8 (33.1-36.6)%, respectively. The corresponding rates in the sacubitril/valsartan group were 13.4 (12.4, 14.5), 22.1 (20.8, 23.4) and 29.5 (27.9, 31.2)%, respectively. Overall 1275 enalapril treated and 1038 sacubitril/valsartan treated patients had an event, giving a hazard ratio 0.79 (95% CI 0.73, 0.86), p<0.0001. Over the course of the trial, 55 fewer patients per 1000 treated with sacubitril/valsartan, compared with enalapril, experienced worsening (number needed to treat = 18). Conclusions: Even in patients with predominantly mild symptoms, well treated with evidence-based pharmacological therapy, worsening of HF over time was common, with more than a third of patients exhibiting progression within 3 years. The ARNI sacubitril/valsartan led to clinically important relative and absolute reductions in progressive worsening, compared with enalapril.

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The power of optimal medical therapy using Angiotensin Receptor-Neprilysin inhibitor (ARNI) in acute decompensated heart failure, sparing a critical patient open-heart surgery with a device therapy

10.22541/au.158931079.94092379 ◽

2020 ◽

Author(s):

Fady Gerges ◽

Austin Komaranchath ◽

Faiz Al bakshy ◽

Wissam Al sahli ◽

Abdallah Almaghraby

Keyword(s):

Heart Failure ◽

Heart Surgery ◽

Acute Decompensated Heart Failure ◽

Open Heart Surgery ◽

Decompensated Heart Failure ◽

Open Heart ◽

Angiotensin Receptor ◽

Device Therapy ◽

Neprilysin Inhibitor ◽

Angiotensin Receptor Neprilysin Inhibitor

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Shift of conventional paradigm of heart failure treatment: from angiotensin receptor neprilysin inhibitor to sodium–glucose co-transporter 2 inhibitors?

Future Cardiology ◽

10.2217/fca-2020-0178 ◽

2021 ◽

Vol 17 (3) ◽

pp. 497-506

Author(s):

Alexander E Berezin ◽

Alexander A Berezin

Keyword(s):

Heart Failure ◽

Wide Spectrum ◽

Large Body ◽

Renin Angiotensin System ◽

Angiotensin Receptor ◽

Heart Failure Treatment ◽

Angiotensin System ◽

Reduced Ejection Fraction ◽

Neprilysin Inhibitor ◽

Angiotensin Receptor Neprilysin Inhibitor

Current clinical guidelines for heart failure (HF) contain a brand new therapeutic strategy for HF with reduced ejection fraction (HFrEF), which is based on neurohumoral modulation through the use of angiotensin receptor neprilysin inhibitors. There is a large body of evidence for the fact that sodium-glucose co-transporter 2 inhibitors may significantly improve all-cause mortality, cardiovascular mortality and hospitalization for HF in patients with HFrEF who received renin–angiotensin system blockers including angiotensin receptor neprilysin inhibitors, β-blockers and mineralocorticoid receptor antagonists. The review discusses that sodium-glucose co-transporter 2 inhibitors have a wide spectrum of favorable molecular effects and contribute to tissue protection, improving survival in HFrEF patients.

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Effects of angiotensin receptor neprilysin inhibitor on renal function in patients with heart failure: a systematic review and meta-analysis

Postgraduate Medical Journal ◽

10.1136/postgradmedj-2021-140132 ◽

2021 ◽

pp. postgradmedj-2021-140132

Author(s):

Yuwu Shi ◽

Yiwen Wang ◽

Junhong Chen ◽

Chi Lu ◽

Haochen Xuan ◽

...

Keyword(s):

Heart Failure ◽

Renal Function ◽

Ejection Fraction ◽

Serum Potassium ◽

Cochrane Library ◽

Control Group ◽

Angiotensin Receptor ◽

Neprilysin Inhibitor ◽

Patients With Heart Failure ◽

Angiotensin Receptor Neprilysin Inhibitor

The angiotensin receptor neprilysin inhibitor (ARNI) has been recommended as a first-line treatment in patients with heart failure (HF). However, the effects of ARNI on renal function remain controversial.The PubMed, Embase, the Cochrane Library of Trials and Web of Science were searched in the period from inception to 31 January 2021. Randomised controlled trial, cohort studies and observational studies reporting at least one of renal function indicators were included.In patients with HF with reduced ejection fraction (HFrEF), ARNI did not lead to a significant decrease in estimated glomerular filtration rate (eGFR, p=0.87), and the risk of worsening renal function (WRF) dropped by 11% compared with control group. Though the level of serum creatinine (SCr) and serum potassium had a slight increase (p=0.01; p=0.02), in contrast to the baseline level, but without clinical significance. In patients with HF with preserved ejection fraction (HFpEF), the level of SCr and serum potassium did not have a significant change, and patients with HFpEF assigned to ARNI had a much lower rate of WRF (p=0.0007). In contrast to control group, both patients with HFrEF and HFpEF had a less decrease in eGFR and a lower rate of hyperkalaemia in ARNI group.ARNI did not lead to a significant decrease in eGFR in HFrEF. Compared with control group, ARNI could delay the progression of decrease in eGFR and result in less events of hyperkalaemia in patients with HF. Besides, patients with HFpEF had a lower rate in the events of WRF.

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