Safety of the neprilysin/renin-angiotensin system inhibitor LCZ696

Bo Li, Yunhe Zhao, Bo Yin, Mengfei Helian, Xinmei Wang, Feng Chen, Hongxia Zhang, Hui Sun, Bin Meng and Fengshuang An _

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Oncotarget. 2017; 8:83323-83333. https://doi.org/10.18632/oncotarget.18312

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Bo Li1,*, Yunhe Zhao1,*, Bo Yin1, Mengfei Helian2, Xinmei Wang2, Feng Chen1, Hongxia Zhang1, Hui Sun1, Bin Meng1 and Fengshuang An3

1Department of Cardiology, Central Hospital of Zibo, Zibo, 255036, PR China

2Department of Pathology, Central Hospital of Zibo, Zibo, 255036, PR China

3Department of Cardiology, Qilu Hospital of Shandong University, Ji’nan, 250012, PR China

*These authors contributed equally to this work

Correspondence to:

Fengshuang An, email: [email protected]

Bin Meng, email: [email protected]

Keywords: heart failure, hypertension, LCZ696, sacubitril/valsartan, safety

Received: March 22, 2017     Accepted: May 23, 2017     Published: May 31, 2017


Objectives: The combined neprilysin/rennin-angiotensin system inhibitor sacubitril/valsartan (LCZ696) has shown its superiority over ACEI/ARB therapy. In view of the existing concern of its adverse effects, we aimed to provide evidence of the safety of the new drug.

Results: A total of 6 randomized trials with 11,821 subjects were included in this analysis. No significant differences were found in any adverse effects between LCZ696 and ACEI/ARB or placebo groups. LCZ696 significantly decreased the risks of serious adverse events and death compared with ACEI/ARB. LCZ696 also significantly decrease the risk of discontinuation of treatment for any adverse event no matter compared with ACEI/ARB or a placebo. LCZ696 significantly increased the risk of angioedema and dizziness, while it decreased the risk of renal dysfunction and bronchitis. There was no difference for hypotension, hyperkalemia, cough, upper respiratory tract inflammation, diarrhoea, back pain, nasopharyngitis, headache and influenza between the LCZ696 group and the ACEI/ARB group.

Materials and Methods: A meta-analysis of eligible studies that used LCZ696 in heart failure and hypertension was performed. Embase, PubMed and the Cochrane Library were searched for randomized controlled trials (RCTs) with data on any adverse effects, serious adverse events, discontinuation of treatment for any adverse event, death, angioedema, hypotension, hyperkalemia, and other adverse effects to perform this meta-analysis.

Conclusions: In addition to the beneficial effect of LCZ696 on end point events, the available evidences showed that LCZ696 was associated with less drug-risks than a placebo and ACEI/ARB.

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