Safety of the neprilysin/renin-angiotensin system inhibitor LCZ696

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.