A Cochrane systematic review of data from 37 trials investigating treatments for HFpEF suggested that evidence is also lacking to support the use of ACE Inhibitors, ARBs or ARNIs in patients with HFpEF at this time, and that the mainstay pharmacological therapy for HFpEF still remains the treatment of co-morbidities such as hypertension or other triggers for decompensation. Concluding in 2019, it failed to show significance for reducing hospitalisation related to heart failure or reducing death from cardiovascular causes, and therefore appearing to show limited benefit to those with HFpEF. To investigate its use for heart failure in those with a preserved LVEF (HFpEF), Novartis funded the PARAGON-HF trial which was designed to investigate the use of sacubatril/valsartan in the treatment of HFpEF patients with a LVEF of 45% or more. Sacubitril/valsartan can be used instead of an ACE inhibitor or an angiotensin receptor blocker in people with heart failure and a reduced left ventricular ejection fraction (LVEF), alongside other standard therapies (e.g. The active form of the molecule, Sacubitrilat, is responsible for the molecule's drug lowering effects. Sacubitril is the molecule that is metabolically activated by de-ethylation by esterases.
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