Erythropoietin role in the therapeutic management of heart failure patients with anemia

The introduction of beta adrenergic blockers associated with angiotensin converting enzyme (ACE) inhibitors in the treatment of HF led to a significant improvement in prognosis.11–13 The benefit obtained with beta-adrenergic blockers encouraged the search for new drugs that not only more completely block the activation of the reninangiotensin and sympathetic systems, but also allow modulating other activated phenomena in heart failure, such as inflammation and endothelial dysfunction.14 However, in recent years we have found that multiple studies analyzing the benefit of new drugs obtained controversial results. From new ACE inhibitors, endothelin and tumor necrosis factor alpha inhibitors, and the same angiotensin receptor antagonists that have brought benefits, but far below the expectations created. This indicates that there is probably no additional benefit to be gained by trying to increase the blockage of circulating neurohormones; in fact, some authors have suggested that this pathway has been exhausted and other therapeutic options must be sought.15 Current guidelines on heart failure recommend the use Sacubitril/ Valsartan (S/V), an angiotensin receptorneprilysin inhibitor, in replacement of the renin–angiotensin–aldosterone system inhibition in ambulatory patients with HF and reduced ejection fraction still symptomatic despite optimal medical therapy.16 This recommendation comes from a single randomized study named PARADIGM-HF trial, which showed the superiority of Sacubitril-Valsartan compared to Enalapril in reducing the incidence of cardiovascular death or hospitalizations for HF.17 Nevertheless, despite the improvements in clinical management and medical therapy of HF, the outcome of these patients still remains poor.18 The persistence of significant ventricular remodeling despite optimized medical treatment has been associated with a poorer prognosis in heart failure. In this sense, possible interventions to cut the signals that activate the mechanisms that mediate progressive ventricular remodeling are being investigated in recent years. Despite the effort made, there is still a long way to go before it can become a reality that allows newer drugs to be generated.19 The lack of effective new treatments has led to a deeper analysis of the factors that affect the prognosis of heart failure, and anemia is one of them. Increasing attention is paid to anemia in patients with HF due to the relationship it has with its prognosis, which, despite all the treatments that have been used in HF, continues to be poor.5,6 This relationship had previously been observed by several authors, both in terms of mortality and the need for new hospital admissions for HF. Furthermore, this association has been observed in hospitalized and outpatients. In fact, anemia is usually frequent in patients with HF in advanced stages of the disease. There is no doubt that correcting anemia can improve symptoms by correcting the oxygen supply to the tissues. Treatment with recombinant erythropoietin (EPO) and parenteral iron improves the functional class, ventricular function, and quality of life of these patients and also reduces the need for diuretics, both oral and intravenous.7–10