title: A dosing algorithm for erythropoietin alpha in older adults with heart failure and a preserved ejection fraction.
abstract: OBJECTIVE
  Erythropoietin stimulating agents (ESAs) is an active area of clinical investigation in heart failure (HF) but can cause hypertension and higher hemoglobin concentrations (Hb) that have been associated with adverse outcomes. We evaluated a dosing algorithm and potential confounders' effect on Hb and blood pressure (BP) in a clinical trial.
  
  
  METHODS
  In an ongoing randomized, placebo controlled, single blind clinical trial of ESA (epoetin alfa) in anemic patients with HF and a preserved ejection fraction (HFPEF), Hb was measured weekly as was BP, weight and concomitant medical therapy. A repeated measure mixed model evaluated determinants of weekly changes in Hb and BP.
  
  
  RESULTS
  Among 45 subjects (78 ± 11 years, 67% women, EF = 57 ± 9%) with a total of 780 repeated weekly Hb measures, Hb significantly increased over time in those assigned to ESA (β = 0.933, P < 0.0001), compared to placebo. Dose (β = -0.108, P < 0.0001), patient weight (β = -0.016, P = 0.0037), diuretic use (β = -0.124, P = 0.0389), and time (β = 0.003, P = 0.0331), were all significantly associated with Hb change. Increased diuretic dose and weight change were significantly inversely associated with changes in Hb. ESA administration and dose were not significant determinants of absolute BP or changes in BP from baseline.
  
  
  CONCLUSIONS
  In addition to ESA dose and duration of therapy, factors indicative of volume status including weight and diuretic use are determinants of hemoglobin levels in HF subjects.
  
  
  CONCLUSIONS
  The currently employed dosing algorithm, which adjusts the administration of ESA based on the absolute hemoglobin and weekly change in hemoglobin increases Hb with relatively a low weekly dose of ESA without significant effects on BP.
authors: Columbia University Medical Center, New York, NY 10034, USA.
authors: Arman
authors: A
authors: Altincatal
authors: Robert B
authors: RB
authors: Macarthur
authors: Sergio
authors: S
authors: Teruya
authors: Stephen
authors: S
authors: Helmke
authors: Mathew S
authors: MS
authors: Maurer
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D000740:Anemia / Q000097:blood / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects; D001810:Blood Volume / Q000187:drug effects; D015986:Confounding Factors, Epidemiologic; D004232:Diuretics / Q000627:therapeutic use; D004334:Drug Administration Schedule; D054796:Drug Dosage Calculations; D000068817:Epoetin Alfa; D004921:Erythropoietin / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006333:Heart Failure / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy / Q000503:physiopathology*; D006397:Hematinics / Q000008:administration & dosage* / Q000009:adverse effects; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D008297:Male; D015999:Multivariate Analysis; D009519:New York City; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects; D016037:Single-Blind Method; D013318:Stroke Volume; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D004232:Diuretics; D006397:Hematinics; D006454:Hemoglobins; D011994:Recombinant Proteins; D004921:Erythropoietin; D000068817:Epoetin Alfa