Safety Of Sacubitril–valsartan In The Treatment Of Heart Failure Compared With ACEI/ARB: A Meta-analysis And Systematic Review

Aims: Sacubitril–valsartan is a new medication used for heart failure recently.The aim of this study is to explore the safety of sacubitril–valsartan compared with ACEI/ARB in the treatment of heart failure(HF)and to systematically review the major adverse events.Background: Heart failure is a severe stage of all kinds of cardiovascular diseases,even though the prognosis of the patients with heart failure was improved by using renin-angiotensin system antagonist and ? blocker,however,5 years of mortality is still high,even higher than some malignant tumors.Fortunately,the PARDDIGM study revealed that sacubitril–valsartan was superior to enalapriln in reducing HF administration and cardiovascular mortality.Hence,sacubitril–valsartan is widely recommended by guideline for the management of HF in clinical practice,the safety of the medication is the key consideration in the clinical practice,but its safety evaluation is limited up to now.Our study performed a meta-analysis,and aimed to explore the safety of sacubitril–valsartan in HF treatment and to review the major adverse events systematically.Methods: Embase,Pub Med,the Cochrane Library and Clinical Trials.gov databases were electronically searched for the available randomized controlled trials(randomizedcontrolled trials,RCTs)with subjects including:“LCZ696”,“AHU377”,“sacubitril /valsartan”,“entresto”,“angiotensin receptor neprilysin inhibitor” and “neprilysin inhibitor”,the latest search was carried out by Sep 20.The primary endpoints of the meta-analysis were safety-related indicators,including the rate of adverse events,the rate of severe adverse events,the rate of renal deterioration,hyperkalemia,hypotension and angioedema.We used Review Manager5.3 for all statistical analyses.Results: Six randomized controlled studies were retrieved and included in this meta-analysis.All the included studies in this meta-analysis were multi-center randomized controlled trials with a total of 14,959 patients,7474 of whom were treated with sacubitril–valsartan and 7485 with ACEI/ARB.Five randomized controlled studies reported the overall incidence of adverse events,and there was little difference(OR =0.91,95% CI 0.83-1.00,P = 0.05)between sacubitril–valsartan and ACEI/ARB group.All of the 6 randomized controlled trials reported the number of people with drug withdrawal due to side effects,and our result showed sacubitril–valsartan did not increase the rate of drug withdrawal(OR = 0.87,95% CI 0.70-1.07,P = 0.1).4studies reported the incidence of serious adverse events,and concluded that the incidence of serious adverse events was similar(OR = 0.7,95% CI 0.55-1.10,P =0.15)between sacubitril–valsartan and ACEI/ARB group.6 studies have reported the rates of worsening renal function,hypotension,hyperkalemia and angioedema,and sacubitril–valsartan significantly reduced the risk of deterioration of renal function(OR = 0.78,95% CI 0.64–0.94,P = 0.008).In addition,the rates of hyperkalemia and angioedema were equivalent in both groups,OR was 0.92 for hyperkalemia(95% CI0.84-1.01,P = 0.0.8)and 1.42 for angioedema(95% CI 0.52-3.89,P = 0.49).To be mindful,sacubitril–valsartan significantly increased rate of hypotension(OR = 1.55,95% CI 1.40-1.71,P < 0.001).Conclusion: Sacubitril–valsartan was not inferior to ACEI/ARB in terms of safety in the treatment of HF,but was superior in reducing the risk of deterioration of renal function.In clinical practice,we need to pay attention to the risk of hypotension.