Why the study?
Does sacubitril/valsartan reduce mortality and morbidity in symptomatic heart failure patients compared to ACE inhibitors?
Does sacubitril/valsartan reduce mortality and morbidity in symptomatic heart failure patients compared to ACE inhibitors?
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Sacubitril/valsartan is a first-in-class ARNI that replaces ACE inhibitors as a foundational therapy for HFrEF, with ongoing trials evaluating its efficacy and long-term cognitive safety in HFpEF.
Sacubitril/valsartan is a novel, first-in-class drug, which combines a neprilysin inhibitor with an angiotensin receptor blocker. Sacubitril inhibits neprilysin endopeptidase, blocking the catabolism of natriuretic peptides (NP), thereby increasing their bioavailability. Valsartan counterbalances the increase of angiotensin II that results from neprilysin inhibition, exerting also the beneficial effects of angiotensin receptor blockers seen in previous HF trials. PARADIGM-HF trial has proved the superiority of sacubitril/valsartan (LCZ696) over ACE inhibitor enalapril to reduce mortality and morbidity of symptomatic HF patients with reduced ejection fraction (HFrEF), setting the grounds for the replacement of ACE inhibitors by sacubitril/valsartan in the management of HFrEF. Sacubitril/valsartan is currently being tested in a phase III trial (PARAGON-HF) in patients with HF with preserved EF. PARAGON-HF is also expected to provide further data regarding the long-term safety of sacubitril/valsartan, hopefully to alleviate concerns regarding the effects of neprilysin inhibition on cognitive function.
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Katsanos et al. (2016) studied this question.
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