However, even before symptoms become manifest, many patients already have evidence of structural and functional abnormalities in the left ventricle (LV), which may be precursors to heart failure. Early recognition of these subclinical precursors is important because they often portend poor outcomes in heart failure patients, and commencement of therapy at the precursor stage may reduce mortality in patients with asymptomatic systolic LV dysfunction.1
Pharmacotherapy is the cornerstone of treatment for HFrEF and should be implemented before considering device therapy, and alongside non-pharmacological interventions.
There are three major goals of treatment for patients with HFrEF: 1) reduction in mortality, 2) prevention of recurrent hospitalisations due to worsening HF, and 3) improvement in clinical status, functional capacity, and quality of life (QoL).2
The European Society of Cardiology still recommends the use of an angiotensin receptor-neprilysin inhibitor (ARNI) as a replacement for an angiotensin-converting enzyme inhibitor (ACE-I) in suitable patients who remain symptomatic on ACE-I, beta-blocker, and MRA therapies; however, an ARNI may be considered as a first-line therapy instead of an ACE-I.2
In the PARADIGM-HF trial, sacubitril/valsartan, an ARNI, was shown to be superior to enalapril in reducing hospitalisations for worsening HF, CV mortality, and all-cause mortality in patients with ambulatory HFrEF with LVEF ≤40% (changed to ≤35% during the study). Patients in the trial had elevated plasma NP concentrations, an eGFR ≥30mL/min/1.73m2 and were able to tolerate enalapril and then sacubitril/valsartan during the run-in period. Additional benefits of sacubitril/ valsartan included an improvement in symptoms and QoL, a reduction in the incidence of diabetes requiring insulin treatment, and a reduction in the decline in eGFR, as well as a reduced rate of hyperkalaemia. Additionally, the use of sacubitril/valsartan may allow a reduction in loop diuretic requirement.
Symptomatic hypotension was reported more commonly in patients treated with sacubitril/valsartan as compared to enalapril, but despite developing hypotension, these patients also gained clinical benefits from sacubitril/valsartan therapy.
Therefore, it is recommended that an ACE-I or ARB is replaced by sacubitril/valsartan in ambulatory patients with HFrEF, who remain symptomatic despite the optimal treatment outlined above. Two studies have examined the use of ARNI in hospitalised patients, some of whom had not been previously treated with ACE-I. Initiation in this setting appears safe and reduces subsequent CV death or HF hospitalisations by 42% compared to enalapril. As such, initiation of sacubitril/valsartan in ACE-I-naïve patients with HFrEF may be considered. Patients being commenced on sacubitril/valsartan should have an adequate BP, and an eGFR ≥30mL/min/1.73m2. A washout period of at least 36h after ACE-I therapy is required in order to minimise the risk of angioedema.
1. Hitzeroth J, Mpe M, Klug E, et al. 2020 Heart Failure Society of South Africa perspective on the 2016 European Society of Cardiology Chronic Heart Failure Guidelines S Afr Med J 2020;110(9b):938-951. https://doi.org/10.7196/SAMJ.2020.v110i8.14681.
2. McDonagh T, Metra M, Adamo M, et al. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. European Heart Journal 2021:42,3599-3726. Doi:10.1093/eurheartj/ehab368.