Correction of anemia with epoetin alfa in chronic kidney disease

N Engl J Med. 2006 Nov 16;355(20):2085-98. doi: 10.1056/NEJMoa065485.

Abstract

Background: Anemia, a common complication of chronic kidney disease, usually develops as a consequence of erythropoietin deficiency. Recombinant human erythropoietin (epoetin alfa) is indicated for the correction of anemia associated with this condition. However, the optimal level of hemoglobin correction is not defined.

Methods: In this open-label trial, we studied 1432 patients with chronic kidney disease, 715 of whom were randomly assigned to receive a dose of epoetin alfa targeted to achieve a hemoglobin level of 13.5 g per deciliter and 717 of whom were assigned to receive a dose targeted to achieve a level of 11.3 g per deciliter. The median study duration was 16 months. The primary end point was a composite of death, myocardial infarction, hospitalization for congestive heart failure (without renal replacement therapy), and stroke.

Results: A total of 222 composite events occurred: 125 events in the high-hemoglobin group, as compared with 97 events in the low-hemoglobin group (hazard ratio, 1.34; 95% confidence interval, 1.03 to 1.74; P=0.03). There were 65 deaths (29.3%), 101 hospitalizations for congestive heart failure (45.5%), 25 myocardial infarctions (11.3%), and 23 strokes (10.4%). Seven patients (3.2%) were hospitalized for congestive heart failure and myocardial infarction combined, and one patient (0.5%) died after having a stroke. Improvements in the quality of life were similar in the two groups. More patients in the high-hemoglobin group had at least one serious adverse event.

Conclusions: The use of a target hemoglobin level of 13.5 g per deciliter (as compared with 11.3 g per deciliter) was associated with increased risk and no incremental improvement in the quality of life. (ClinicalTrials.gov number, NCT00211120 [ClinicalTrials.gov].).

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Anemia / complications
  • Anemia / drug therapy*
  • Epoetin Alfa
  • Erythropoietin / adverse effects
  • Erythropoietin / therapeutic use*
  • Female
  • Glomerular Filtration Rate
  • Heart Failure / epidemiology
  • Heart Failure / etiology
  • Hematinics / adverse effects
  • Hematinics / therapeutic use*
  • Hemoglobins / analysis*
  • Hospitalization
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Myocardial Infarction / epidemiology
  • Myocardial Infarction / etiology
  • Recombinant Proteins
  • Renal Insufficiency, Chronic / blood
  • Renal Insufficiency, Chronic / complications*
  • Renal Insufficiency, Chronic / mortality
  • Stroke / epidemiology
  • Stroke / etiology
  • Survival Analysis

Substances

  • Hematinics
  • Hemoglobins
  • Recombinant Proteins
  • Erythropoietin
  • Epoetin Alfa

Associated data

  • ClinicalTrials.gov/NCT00211120