https://orcid.org/0000-0002-5446-9969
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Kieran F Docherty, John J V McMurray, PIONEER-HF: a new frontier in the role of neprilysin inhibition in the management of heart failure with reduced ejection fraction, Cardiovascular Research, Volume 115, Issue 13, 1 November 2019, Pages e136–e139, https://doi.org/10.1093/cvr/cvz223
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The addition of a neprilysin inhibitor to a renin–angiotensin system (RAS) antagonist, using the combination of sacubitril and valsartan, was shown to reduce morbidity and mortality in outpatients with chronic heart failure and reduced ejection fraction (HFrEF).1 In PARADIGM-HF (Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure trial), sacubitril/valsartan reduced the risk of cardiovascular death or heart failure (HF) hospitalization by 20%, compared with a RAS blocker alone [the gold-standard angiotensin-converting enzyme (ACE)-inhibitor enalapril]. Consequently, international guidelines have recommended adding a neprilysin inhibitor in patients with HFrEF who remain symptomatic despite treatment with a RAS antagonist, beta-blocker, and mineralocorticoid receptor antagonist [by switching from existing ACE-inhibitor or angiotensin II receptor blocker (ARB) to sacubitril/valsartan].2 However, there remained a series of unanswered questions as to the role of sacubitril/valsartan in particular subgroups of patients: PARADIGM-HF did not recruit hospitalized patients; it required patients to be tolerant of maximal doses of both enalapril and sacubitril/valsartan during sequential single-blinded run-in periods prior to randomization; and it did not include patients who were ACE-inhibitor or ARB naïve.
