HFREF Therapy: Randomized Evidence and Real-World Perspectives

Abstract

Heart failure with reduced ejection fraction (HFrEF) has seen significant therapeutic advances with the consolidation of the four pharmacological pillars that modify prognosis. The widespread use of these therapies is associated with a substantial reduction in cardiovascular death and hospitalizations for heart failure, supporting contemporary strategies for rapid introduction and subsequent optimization to target or maximum tolerated doses. In this context, sacubitril/valsartan demonstrated prognostic benefit in PARADIGM-HF and a greater reduction in NT-proBNP in PIONEER-HF. However, different results were observed in other settings, such as PARADISE-MI and LIFE, helping to define the populations in which its benefit was demonstrated. The study published in this issue of the Arquivos Brasileiros de Cardiologia evaluated, in a real-world observational cohort, patients with HFrEF treated with maximum doses of sacubitril/valsartan, enalapril, or losartan. Compared to the group treated with enalapril or losartan, sacubitril/valsartan was not associated with a statistically significant reduction in hospitalization or mortality, although it was associated with an improvement in functional class. These findings should be interpreted considering methodological limitations, such as observational design, lack of randomization, limited number of events, and heterogeneity of the comparator group. Real-world studies broaden the understanding of the effectiveness, applicability, and implementation of therapies and should be analyzed in conjunction with the consolidated evidence from randomized clinical trials.

Heart failure (HF) is a complex and serious syndrome associated with high hospitalization and mortality rates. In heart failure with reduced ejection fraction (HFrEF), large clinical trials have established four pharmacological pillars that modify the prognosis: beta-blockers, which attenuate the activation of the sympathetic nervous system; inhibition of the renin-angiotensin system, through the use of angiotensin receptor and neprilysin inhibitors (ARNIs), angiotensin-converting enzyme inhibitors (ACEIs), or angiotensin receptor blockers (ARBs); mineralocorticoid receptor antagonists (MRAs); and sodium-glucose cotransporter type 2 inhibitors (SGLT2i).^,

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