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Am Fam Physician. 2022;105(6):online

Clinical Question

Is sacubitril/valsartan (Entresto) safe and effective for improving patient-oriented outcomes in adults with heart failure and preserved ejection fraction?

Bottom Line

The addition of sacubitril/valsartan to the treatment regimen of adults with heart failure and preserved ejection fraction significantly decreased plasma N-terminal pro–brain natriuretic peptide (NT-proBNP) levels compared with standard renin-angiotensin system (RAS) inhibitor treatment or placebo. However, no patient-oriented outcomes were significantly improved, including the six-minute walk distance, quality-of-life scores, or New York Heart Association (NYHA) class. (Level of Evidence = 1b)


The investigators identified adults, 45 years and older, with symptomatic heart failure, elevated NT-proBNP levels, NYHA class II through IV, a left ventricular ejection fraction of greater than 40%, and an impaired health-related quality of life as measured by a standard scoring tool. Patients taking an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin receptor blocker (ARB) at baseline were required to have a history of hypertension. Eligible participants (N = 2,566) were initially assigned to one of three strata based on medication prescribed by their treating clinician: ACE inhibitor (n = 1,066), ARB (n = 1,174), or no RAS inhibitor (n = 326). Within each stratum, patients randomly received (concealed allocation assignment) sacubitril/valsartan or the background medication (i.e., ACE inhibitor, ARB, or placebo/no RAS inhibitor). Clinicians were instructed to up-titrate within four weeks to the maximally tolerated doses. Patients, clinicians, and individuals assessing outcomes remained masked to treatment group assignment. Complete follow-up occurred for more than 99% of patients at 24 weeks. 

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POEMs (patient-oriented evidence that matters) are provided by Essential Evidence Plus, a point-of-care clinical decision support system published by Wiley-Blackwell. For more information, see Copyright Wiley-Blackwell. Used with permission.

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