Chronic Heart Failure (CHF) Condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Can be caused by structural defects, functional abnormalities (ventricular dysfunction).   Kenneth D., Alain C., et al. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2008. Eur. HeartJ. 2008; 29: 2388-2442.
Classification of the different grades of CHF ClassPatient Symptoms Class I (Mild)No limitation of physical activity. Class II (Mild)Slight limitation of physical activity. Class III (Moderate) Marked limitation of physical activity. Class IV (Severe) Unable to carry out any physical activity without discomfort. New York Heart Association
Anaemia Anemia is defined as a qualitative or quantitative deficiency of hemoglobin According to the World Health Organization (WHO) Haemoglobin concentration <12g/dL in women and <13g/dL in men indicates the presence of anemia.  Vedhuisen D., Dickstein K., et al. Randomized double-blind, placebo- controlled study to evaluate the effect of two dosing regimens of darbepoetin alfa in patients with heart failure and anaemia. Eur. HeartJ.2007;28.
Anaemia in CHF Prevalence of anaemia depends both on the severity of CHF and diagnostic criteria used to define it  Anaemia is present in one-third of the CHF patients (WHO)   Dunlay S., Weston S., et al. Anemia and heart failure: A community study. Acad Med 2008; 121: 726-732.
Erythropoietin (EPO) Erythropoietin (EPO) is a glycoprotein hormone secreted chiefly by the kidney. The kidney cells that make EPO are sensitive to low oxygen levels in the blood coming into the kidney. These cells make and release EPO when the oxygen level is too low
More RBCs Normal blood oxigen levels Reduced O 2 levels in blood Kidney releases erythropoietin Erythropoietin stimulates Red bone marrow Increased O 2 - carrying ability of blood Enhanced erythropoiesis
Erythropoietin in other diseases Oncology - Quimioterapy reduces the levels of red blood cells.  Kidney failure - There is no production of erythropoietin.  Crawford J., Recombinant human erythropoietin in cancer-related anemia. Review of clinical evidence. Oncology 2002;16: 41-53 Michael J., Lloyd I., et al. Impact of epoetin alfa on clinical end points in patients with chronic renal failure: A meta-analysis.Kidney International 2004; 65: 757–76.
Study Question Does the treatment of anaemia with erythropoietin stimulating proteins improve survival and quality of life of severe heart failure patients?
Study Aims 1.Evaluate if severe heart failure patients with anaemia treated with erythropoietin stimulating proteins have reduction in mortality rates and improvement in the prognosis: readmission rates, NYHA functional class and the improvement in the quality of life; 2.Determine complication rates and safety of erythropoietin stimulating proteins treatment.
Methods Method Systematic Review of Randomized Controlled Trials Database search Medline Scopus ISI Web of Knowledge
Query For PubMed search: ("Heart Failure“ [Mesh] OR "heart failure“ [All Fields] OR "congestive heart failure“ [All Fields] OR "chronic heart failure“ [All Fields] OR "systolic dysfunction“ [All Fields] OR "symptomatic heart failure“ [All Fields]) AND ("Anemia“ [Mesh] OR "anaemia“ [All Fields] OR "anemia“ [All Fields]) AND ("Erythropoietin, Recombinant“ [Mesh] OR "epoetin delta“ [Substance Name] OR "erythropoiesis stimulating protein, human“ [Substance Name] OR "darbepoetin alfa“ [Substance Name] OR "recombinant erythropoietin“ [All Fields] OR "erythropoietin“ [All Fields] OR "erythropoietin“ [MeSH Terms] OR "erythropoietin recombinant“ [All Fields]) For ISI Web of Knowledge, Cochrane and Scopus the query is the same with slight modifications
Exclusion CriteriaInclusion Criteria - Comparison of erythropoietin with other drugs - Randomized controlled clinical trial - Full article isn’t available- Erythropoietin group or erythropoietin + iron therapy vs placebo group or iron therapy - Animal experimentation- Articles where in the 2 groups the heart failure treatment is optimise -Articles not from Journal of the American College neither from European Heart Journal (scopus) - Articles that evaluate prognosis, mortality and quality of life - Article in other language which not English or Portuguese - Articles that study erythropoietin therapy in other diseases (not heart failure) - Review articles, letters, comments, editorials