title: Erythropoiesis-stimulating agents and thrombotic events in dialysis patients.
abstract: BACKGROUND
  Erythropoiesis-stimulating agents (ESA) have been associated with a higher cardiovascular event and mortality rate in dialysis patients. The ESA-associated risk of arterial thrombotic events is mainly based on composite endpoints of anemia-correction trials targeting high hemoglobin levels. The ESA-associated risk of venous thromboembolism (VTE) has not been studied in dialysis patients yet. We therefore aimed to determine the association between ESA use and dose with ischemic stroke, myocardial infarction (MI) and VTE.
  
  
  METHODS
  In NECOSAD, a Dutch cohort study of incident dialysis patients, data on ESA use and dose, comorbidities and laboratory parameters were routinely collected every 6 months. Thrombotic events were collected by chart review of all dialysis patients from 6 participating centers. Time-dependent Cox regression analysis was performed to calculate hazard ratios (HR) with 95% confidence interval (CI) for ischemic stroke, MI and VTE with updated information on ESA use and dose.
  
  
  RESULTS
  Patients with ESA had a 2 times lower ischemic stroke rate than patients without ESA: adjusted HR 0.45 (95% CI 0.23-0.90), and an adjusted HR of 1.12 (95% CI 0.58-2.14) for MI. No evident ESA dose response effect was present. Unadjusted HR for VTE was 0.41 (95% CI 0.11-1.50) for patients with ESA compared to patients without, but the low event rate made further adjustments impossible.
  
  
  CONCLUSIONS
  In our observational cohort of dialysis patients, reflecting everyday clinical practice, ESA was not associated with an excess of thrombotic events. Further investigation is needed to enlighten the true cause of ESA-associated cardiovascular events and mortality.
authors.affiliation: Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: M.M.Suttorp@lumc.nl.
authors.forename: Marit M
authors.initials: MM
authors.lastname: Suttorp
authors.affiliation: Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Tiny
authors.initials: T
authors.lastname: Hoekstra
authors.affiliation: Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Gürbey
authors.initials: G
authors.lastname: Ocak
authors.affiliation: Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands; Department of Nephrology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Anouk T N
authors.initials: AT
authors.lastname: van Diepen
authors.affiliation: Deutsches Herzzentrum der Technischen Universität München, Munich, Germany.
authors.forename: Ilka
authors.initials: I
authors.lastname: Ott
authors.affiliation: Department of Medicine, Tel Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv, Israel.
authors.forename: Moshe
authors.initials: M
authors.lastname: Mittelman
authors.affiliation: Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Ton J
authors.initials: TJ
authors.lastname: Rabelink
authors.affiliation: Department of Nephrology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Raymond T
authors.initials: RT
authors.lastname: Krediet
authors.affiliation: Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Friedo W
authors.initials: FW
authors.lastname: Dekker
mesh_terms: D000328:Adult; D000368:Aged; D015331:Cohort Studies; D004920:Erythropoiesis / Q000187:drug effects; D005260:Female; D006397:Hematinics / Q000009:adverse effects*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000139:chemically induced; D016016:Proportional Hazards Models; D006435:Renal Dialysis / Q000009:adverse effects; D020521:Stroke / Q000139:chemically induced; D054556:Venous Thromboembolism / Q000139:chemically induced*
chemical_list: D006397:Hematinics
keywords: Chronic kidney disease; Dialysis; Erythropoietin; Ischemic stroke; Myocardial infarction; Venous thrombosis