Pharmacotherapy in heart failure with reduced ejection fraction during the last 20 years, and the way ahead for precision medicine.

Abstract

There are but a few areas in medicine, where progress has been as remarkable as in heart failure (HF) therapy over the three last decades. However, progress has been consistent only for chronic HF with reduced ejection fraction (HFREF). As a result of progress made in HFREF therapy, cumulative mortality benefit amounts to almost a three-fold decrease in death rate whether in severe or in mild-to-moderate HFREF. In acutely, decompensated HF (AHF)1,2 as well as in HF with preserved ejection fraction,3 despite a reasonable number of trials, none of the tested therapies so far has definitively been proved to be effective. In chronic HEFREF, it is now well established that triple therapy with angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB), beta-blockers (BB), and mineralocorticoid receptor antagonists (MRA) save lives and prevent hospital re-admission, and unless contraindicated, should be used in all symptomatic patients with HEFREF. In asymptomatic patients, only ACEi therapy has been proved to slow the progression of the disease with mortality and morbidity benefit. No trial has tested so far the benefit–risk ratio of ARBs, BBs, or MRAs in patients with low EF and no symptoms.4 Further progress is announced with the premature termination for excess of benefit of the prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure (PARADIGM–HF) trial,5 with the dual angiotensin receptor and neprilysin inhibition as an alternative to angiotensin-converting enzyme inhibition in patients with chronic systolic HF. Still, admission for worsening HF confers a higher risk of death and/or re-admission and identifies patients with higher needs for therapy optimization. In all HFREF trials with ACEi, ARBs, BBs, and MRAs, therapy was initiated in patients with stable conditions, significantly long after discharge from an HF hospitalization, if any … [↵][1]*Corresponding author. Tel: +33 383157320, Fax: +33 383157319, Email: f.zannad{at}chu-nancy.fr [1]: #xref-corresp-1-1