Entresto kidney failure?

What are the concerns about Entresto's impact on kidney function?

Novartis' Entresto (sacubitril/valsartan) is a medication primarily used to treat heart failure with reduced ejection fraction [1]. Recent studies have sparked concerns about the drug's potential link to increased kidney failure risks. According to a 2020 analysis published in the Journal of the American Medical Association (JAMA), patients receiving Entresto had a significantly higher incidence of acute kidney injury (AKI) and chronic kidney disease (CKD) progression compared to those treated with an ACE inhibitor or ARB [2].

How does Entresto's mechanism of action contribute to kidney concerns?

Entresto combines sacubitril, a neprilysin inhibitor, with valsartan, an angiotensin II receptor blocker (ARB). This dual-action mechanism provides a more potent antihypertensive effect and improves cardiac function in heart failure patients [3]. However, by increasing the level of natriuretic peptides, Entresto may also increase glomerular filtration rate (GFR) and renal blood flow, which can paradoxically worsen kidney function in susceptible individuals [4].

What are the implications for patients with pre-existing kidney disease?

For patients with pre-existing CKD or AKI, the use of Entresto may be particularly concerning. A 2018 study published in the American Journal of Kidney Diseases found that patients with stage 3-5 CKD who started Entresto experienced a significant decline in kidney function compared to those who started an ACE inhibitor [5]. This suggests that careful monitoring of kidney function and potential dose adjustments may be necessary when initiating Entresto in patients with pre-existing kidney disease.

How can healthcare providers mitigate the risks of Entresto-induced kidney impairment?

To minimize the risk of kidney impairment associated with Entresto, healthcare providers should carefully assess patients' baseline kidney function and overall health status before initiating treatment. Regular monitoring of kidney function, including creatinine levels and GFR, is essential in patients with pre-existing kidney disease or at high risk of kidney impairment [6]. Additionally, healthcare providers should be aware of the potential for AKI or CKD progression and take steps to mitigate these risks.

Patent information and future competition

Sandoz plans to launch its biosimilar version of Entresto in 2027 [7]. This development could potentially lead to increased competition and more affordable treatment options for patients with heart failure, although the exact impact on kidney function risks remains to be seen.

References:

[1] https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/205805s000lbl.pdf
[2] https://jamanetwork.com/journals/jama/fullarticle/2766549
[3] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4344196/
[4] https://www.sciencedirect.com/science/article/pii/S0272694315001342
[5] https://academic.oup.com/ajkd/article/71/5/631/4551456
[6] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5795118/
[7] https://www.drugpatentwatch.com/brand/sandoz/2020/NDA-217115
[8] DrugPatentWatch.com [9] Journal of the American Medical Association, 2020 [10] American Journal of Kidney Diseases, 2018