1. TREATMENT OF ANEMIA WITH DARBEPOETIN ALFA IN SYSTOLIC HEART FAILURE Karl Swedberg, M.D., Ph.D., James B. Young, M.D., Inder S. Anand, M.D., Sunfa Cheng, M.D., Akshay S. Desai, M.D., Rafael Diaz, M.D., Aldo P. Maggioni, M.D., John J.V. McMurray, M.D., Christopher O’Connor, M.D., Marc A. Pfeffer, M.D., Ph.D., Scott D. Solomon, M.D., Yan Sun, M.S., Michal Tendera, M.D., and Dirk J. van Veldhuisen, M.D., Ph.D., n engl j med 368;13 nejm.1210 org march 28, 2013 Pf. 김우식 / R2 김형오

2. Introduction  Anemia with heart failure  Common  Lower functional capacity  May be related to erythropoietin deficiency / resistance Impaired renal function, use of renin-angiotensin blockers  Erythropoiesis-stimulating agent(ESA) in HF patients with anemia  Improve functional capacity  Reduce hospitalization  Have not improved cardiovascular outcome  Increased the risk of atherothrombotic events

3. Purpose  Reduction of Events by Darbepoetin Alfa in Heart Failure(RED-HF)  To determine whether treatment with darbepoetin alfa improves clinical outcomes in patients with chronic systolic heart failure and anemia that is not due to iron deficiency

4. Methods  Patients  NYHA functional class II, III, IV heart failure  LV EF 40% or less  Hb 9.0~12.0g/dL  Guideline recommended heart failure therapy  Exclusion criteria Transferrin saturation less than 15% Evidence of bleeding Other correctible causes of anemia Creatinine more than 3mg/dL BP more than 160/100mmHg

5. Methods  Study procedure  Randomly assigned in a 1:1 ratio Darbepoetin alfa or placebo  Darbepoetin alfa 0.75ug/kg, SC injection, once every 2 weeks Until Hb 13.0g/dL reached on 2 consecutive visits Monthly injected thereafter Maximum dose 300ug, once every 2 weeks  Iron supply Iron supplied when transferrin saturation fell to less than 20%

6. Methods

7. Results

8.  Hemoglobin values –Median level of Hb : Darbepoetin alfa 13.0g/dL, placebo 11.5g/dL (p<0.001)

9. Results  Anemia treatments in addition to the study drug  At least one dose of nonstudy ESA 40 of darbepoetin alfa group (3.5%) 77 of placebo group (6.7%)  IV iron 4.9% in the darbepoetin alfa group 5.6% in the placebo group  Oral iron 72.3% darbepoetin alfa group 73.5% placebo group  Transfusion 123 of darbepoetini alfa group(10.9%) 188 of placebo group(16.5%)

10. Results

11.  Kansas city cardiomyopathy questionaire (KCCQ)  Overall Summary Score Mean-changes from baseline to month 6 6.68 in the darbepoetin alfa group, 4.48 in the placebo group 95% CI, p=0.005 Improvement 5 points or more from baseline to month 6 53% in the darbepoetin alfa group, 48% in the placebo group P=0.06  Symptom frequency score Increase from baseline to month 6 6.20 in the darbepoetin alfa group, 3.91 in the placebo group 95% CI, p=0.01

12. Results

13.  Correction of anemia with darbepoetin alfa did not reduce the rate of death or hospitalization among patients with systolic heart failure.  There was a significant increase in the risk of thromboembolic events among patients receiving darbepoetin alfa.