Erythropoiesis-stimulating agent use among non-dialysis-dependent CKD patients before and after the trial to Reduce Cardiovascular Events With Aranesp Therapy (TREAT) using a large US health plan database

Am J Kidney Dis. 2014 Nov;64(5):706-13. doi: 10.1053/j.ajkd.2014.05.013. Epub 2014 Jul 8.


Background: In a landmark study, TREAT (Trial to Reduce Cardiovascular Events With Aranesp Therapy) examined the use of erythropoiesis-stimulating agent (ESA) therapy to treat anemia among patients with chronic kidney disease (CKD) and found no benefit compared to placebo.

Study design: A retrospective observational design was used to determine the impact of TREAT on clinical practice.

Setting & participants: A large US health plan database with more than 1.2 million claims for patients with non-dialysis-dependent CKD stages 3 and 4.

Factor: ESA prescribing 2 years before and after publication of TREAT.

Outcomes: Rate of ESA prescribing for ESA-naive and -prevalent cohorts.

Measurements: (1) Monthly ESA prescribing in the 2 years before and after publication of TREAT (ordinary least squares regression), (2) adjusted likelihood of prescribing ESA after TREAT (clustered logistic regression), and (3) probability of receiving ESA therapy based on anemia status (χ(2) test).

Results: For patients with CKD stage 3, the proportion prescribed ESA therapy declined from 17% pre-TREAT to 11% post-TREAT (a 38% decline), and for those with CKD stage 4, from 34% to 27% (a 22% decline). Prescribing of ESA therapy was declining even before TREAT, but the decline accelerated in the post-TREAT period (stage 3: change of slope, -0.08 [P<0.001]; stage 4: change of slope, -0.16 [P<0.001]). ESA prescribing declined after TREAT regardless of anemia status; among patients with hemoglobin levels <10g/dL, only 25% of patients with CKD stage 3 and 33% of patients with stage 4 were prescribed ESAs 2 years after TREAT, a notable 50% decline. After adjusting for all covariates, the probability of prescribing ESAs was 35% lower during the 2-year period after versus before publication of TREAT (OR, 0.65; 95% CI, 0.63-0.67).

Limitations: The cumulative effect of adverse safety concerns in the period before TREAT also influenced physician prescribing of ESA therapy and could not be separated from the influence of TREAT.

Conclusions: TREAT appears to be a watershed study that was followed by a marked decline in ESA prescribing for patients with CKD.

Keywords: Choose Wisely campaign; Erythropoietin-stimulating agent (ESA); MarketScan; TREAT (Trial to Reduce Cardiovascular Events With Aranesp Therapy); Thomson Reuters; anemia; darbepoetin; epoetin (EPO); hemoglobin; predialysis chronic kidney disease (CKD); prescribing patterns.

Publication types

  • Comparative Study
  • Observational Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Cardiovascular Diseases / chemically induced*
  • Cardiovascular Diseases / epidemiology
  • Cardiovascular Diseases / prevention & control*
  • Cohort Studies
  • Darbepoetin alfa
  • Databases, Factual / trends
  • Erythropoiesis / drug effects*
  • Erythropoiesis / physiology
  • Erythropoietin / adverse effects
  • Erythropoietin / analogs & derivatives*
  • Erythropoietin / pharmacology
  • Female
  • For-Profit Insurance Plans / trends
  • Humans
  • Male
  • Medicare / trends
  • Middle Aged
  • Renal Dialysis*
  • Renal Insufficiency, Chronic / epidemiology
  • Renal Insufficiency, Chronic / therapy*
  • Retrospective Studies
  • Treatment Outcome
  • United States / epidemiology


  • Erythropoietin
  • Darbepoetin alfa