Dataset Information

Low versus high dose erythropoiesis-stimulating agents in hemodialysis patients with anemia: A randomized clinical trial.

ABSTRACT: The increased risks of death and adverse events with erythropoiesis-stimulating agent (ESA) therapy targeting a higher hemoglobin level are established. It is uncertain whether the adverse effects of ESA therapy are related to dose and are mitigated when a fixed low ESA dose is used. We conducted a multicenter, prospective randomized open-label, blinded-endpoint (PROBE) trial to evaluate fixed low versus high dose ESA therapy on patient outcomes. We intended to recruit 2104 hemodialysis patients >18 years with anemia or receiving ESA treated at dialysis clinics in Italy. The intervention was fixed low (4000 IU epoetin alfa equivalent weekly) or high (18,000 IU epoetin alfa equivalent weekly) dose ESA for 12 months. Primary outcomes were serum transferrin, ferritin, albumin, C-reactive protein and ESA dose. Secondary outcomes were the composite of death or cardiovascular event, all-cause mortality, cardiovascular mortality, myocardial infarction, stroke, cardiovascular hospitalization, and quality of life. Study recruitment was terminated after inclusion of 656 participants with convergence of ESA dose between groups during follow up. Fixed low dose ESA had uncertain effects on serum ferritin (delta of delta (DD) 3.9 ng/ml, 95% CI -85.0 to 92.8), transferrin (9.2 mg/dl, -6.3 to 24.8), transferrin saturation (3.7%, -5.0 to 12.3), serum albumin (-0.03 g/dl, -0.2 to 0.1), or C-reactive protein (-0.6 mg/l, -3.3 to 2.1). In addition, fixed dose therapy had inconclusive effects on the composite endpoint of mortality and cardiovascular events (hazard ratio [HR] 0.95, 95% CI 0.66 to 1.37), death (0.98, 0.64 to 1.52), nonfatal myocardial infarction (0.52, 0.18 to 1.52), nonfatal stroke (no events), hospital admission for cardiovascular causes (0.93, 0.50 to 1.72) or health-related quality of life. A fixed low ESA dose in hemodialysis patients has uncertain effects on serum parameters, mortality, cardiovascular events, and quality of life. Hemoglobin targets may be so entrenched in nephrology practice that a trial of ESA dose is no longer possible.

SUBMITTER: Saglimbene V

PROVIDER: S-EPMC5332066 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Low versus high dose erythropoiesis-stimulating agents in hemodialysis patients with anemia: A randomized clinical trial.

Saglimbene Valeria V Palmer Suetonia C SC Craig Jonathan C JC Ruospo Marinella M Nicolucci Antonio A Tonelli Marcello M Johnson David D Lucisano Giuseppe G Williams Gabrielle G Valentini Miriam M D'Alonzo Daniela D Pellegrini Fabio F Strippoli Paolo P Salomone Mario M Santoro Antonio A Maffei Stefano S Hegbrant Jörgen J Tognoni Gianni G Strippoli Giovanni F M GF

PloS one 20170301 3

The increased risks of death and adverse events with erythropoiesis-stimulating agent (ESA) therapy targeting a higher hemoglobin level are established. It is uncertain whether the adverse effects of ESA therapy are related to dose and are mitigated when a fixed low ESA dose is used. We conducted a multicenter, prospective randomized open-label, blinded-endpoint (PROBE) trial to evaluate fixed low versus high dose ESA therapy on patient outcomes. We intended to recruit 2104 hemodialysis patients ...[more]

PMID: 28249030

Similar Datasets

Project description:Targeting higher hemoglobin levels with erythropoiesis-stimulating agents (ESAs) to treat the anemia of chronic kidney disease (CKD) is associated with increased cardiovascular risk.Metaregression analysis examining the association of ESA dose with adverse outcomes independent of target or achieved hemoglobin level.Patients with anemia of CKD irrespective of dialysis status.We searched MEDLINE (inception to August 2010) and bibliographies of published meta-analyses and selected randomized controlled trials assessing the efficacy of ESAs for the treatment of anemia in adults with CKD, with a minimum 3-month duration. Two authors independently screened citations and extracted relevant data. Individual study arms were treated as cohorts and constituted the unit of analysis.ESA dose standardized to a weekly epoetin alfa equivalent, and hemoglobin levels.All-cause and cardiovascular mortality, cardiovascular events, kidney disease progression, or transfusion requirement.31 trials (12,956 patients) met the criteria. All-cause mortality was associated with higher (per epoetin alfa-equivalent 10,000-U/wk increment) first-3-month mean ESA dose (incidence rate ratio [IRR], 1.42; 95% CI, 1.10-1.83) and higher total-study-period mean ESA dose (IRR, 1.09; 95% CI, 1.02-1.18). First-3-month ESA dose remained significant after adjusting for first-3-month mean hemoglobin level (IRR, 1.48; 95% CI, 1.02-2.14), as did total-study-period mean ESA dose adjusting for target hemoglobin level (IRR, 1.41; 95% CI, 1.08-1.82). Parameter estimates between ESA dose and cardiovascular mortality were similar in magnitude and direction, but not statistically significant. Higher total-study-period mean ESA dose also was associated with increased rate of hypertension, stroke, and thrombotic events, including dialysis vascular access-related thrombotic events.Use of study-level aggregated data; use of epoetin alfa-equivalent doses; lack of adjustment for confounders.In patients with CKD, higher ESA dose might be associated with all-cause mortality and cardiovascular complications independent of hemoglobin level.

Dataset Information

Low versus high dose erythropoiesis-stimulating agents in hemodialysis patients with anemia: A randomized clinical trial.

Publications

Low versus high dose erythropoiesis-stimulating agents in hemodialysis patients with anemia: A randomized clinical trial.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets