Efficacy of Sacubitril/Valsartan in the Setting of Acute Heart Failure: A Systematic Review

Abstract

Acute decompensated heart failure (ADHF) is one of the conditions associated with high rates of mortality and morbidity, in addition to its economic burden. Sacubitril/valsartan, the emerging drug in the field of heart failure, has been showing favorable outcomes in patients with heart failure with reduced ejection fraction (HFrEF). However, its efficacy in patients with acute decompensated heart failure remains obscure. This systematic review aims to offer more clarity to this established gap of knowledge. PubMed, ScienceDirect, and ScienceOpen were explored to gain access to studies on this topic. We conducted a systematic review to evaluate the safety and efficacy of using sacubitril/valsartan in the acute setting. Five clinical trials, 10 observational studies, including two abstracts, in addition to seven case reports and one editorial, were obtained and analyzed. Key outcomes of interest were safety and tolerability, efficacy reflected by N-terminal proB-type natriuretic peptide (NT-proBNP), and other serum and echocardiographic parameters. Additionally, target dose attainment, rehospitalization rates, and hemodynamics effect were also outcomes of interest. Based on our findings, the use of sacubitril/valsartan in patients with ADHF and cardiogenic shock is an effective measure. Although most of the results pointed to its safety, some of them showed the outcome of serious adverse events recommending its cautious use.

Sacubitril/valsartan in heart failure: efficacy and safety in and outside clinical trials

“…In a recent systematic review, the management of clinically stabilized patients hospitalized for ADHF with S/V significantly reduces the risk of serious clinical events and reduces NT‐proBNP concentrations 46 …”

“…In a recent systematic review, the management of clinically stabilized patients hospitalized for ADHF with S/V significantly reduces the risk of serious clinical events and reduces NT-proBNP concentrations. 46 As such, initiation of S/V in ACEi-naïve patients with HFrEF may be considered (class of recommendation IIb, level of evidence B). 43 In the recent LIFE investigator-initiated trial, performed in patients with advanced HFrEF who experienced New York Heart Association (NYHA) class IV symptoms within the previous 3 months or required chronic inotropic therapy, no statistically significant differences between S/V and valsartan with respect to reducing NT-proBNP levels (primary outcome) and clinical outcomes (secondary and tertiary outcomes) were observed.…”

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“…Sacubitril/valsartan is illustrative of a combination agent [combining an angiotensin receptor-neprilysin inhibitor (ARNI) with an angiotensin receptor blocker ACE inhibitors] with potential benefits in treating heart failure. [230] ARBs should not be used together and should not be used in combination with direct renin inhibitors (i.e., aliskiren), largely due to questionable added benefits, and potential for hyperkalemia. [ 208 , 231 ] Calcium channel blocker (CCBs) may help treat angina and cardiac dysrhythmias; however, dihydropyridine CCBs (e.g., amlodipine, nifedipine) may cause edema and non-dihydropyridine CCBs (e.g., verapamil and diltiazem) may cause bradycardia and heart block and should be avoided in patients with heart failure with reduced left ventricular ejection fraction.…”

“…Sacubitril/valsartan is illustrative of a combination agent [combining an angiotensin receptor-neprilysin inhibitor (ARNI) with an angiotensin receptor blocker ACE inhibitors] with potential benefits in treating heart failure. [230] ARBs should not be used together and should not be used in combination with direct renin inhibitors (i.e., aliskiren), largely due to questionable added benefits, and potential for hyperkalemia. [ 208 , 231 ]…”