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Abstract: SA-OR37

Time-Dependent Covariate Analysis of Hemoglobin Values on Risk of Major Adverse Cardiovascular Events in the ASCEND Trials

Session Information

Category: Anemia and Iron Metabolism

  • 200 Anemia and Iron Metabolism


  • Obrador, Gregorio T., Universidad Panamericana School of Medicine, Mexico City, Mexico
  • Johansen, Kirsten L., Hennepin Healthcare, Minneapolis, Minnesota, United States
  • Waikar, Sushrut S., Boston University School of Medicine and Boston Medical Center, Boston, Massachusetts, United States
  • Jha, Vivekanand, George Institute for Global Health, New Delhi, India
  • Correa-Rotter, Ricardo, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
  • Del Vecchio, Lucia, Azienda Socio Sanitaria Territoriale Lariana, Como, Italy
  • Cases, Aleix, Universitat de Barcelona, Barcelona, Spain
  • Robertson, Michele, Robertson Centre for Biostatistics, University of Glasgow, Glasgow, United Kingdom
  • Mallett, Stephen, R&D, GSK, Brentford, United Kingdom
  • Bailey, Christine K., R&D, GSK, Collegeville, Pennsylvania, United States
  • Cobitz, Alexander Ralph, R&D, GSK, Collegeville, Pennsylvania, United States
  • Singh, Ajay K., Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, United States

The evidence supporting an association between rapid changes in hemoglobin (Hb) and cardiovascular (CV) outcomes is limited. We performed a time-dependent covariate analysis in patients with chronic kidney disease on dialysis (ASCEND-D, NCT02879305) or not on dialysis (ASCEND-ND, NCT02876835) treated with daprodustat or erythropoiesis-stimulating agent (ESA).


ASCEND-D and ASCEND-ND were event-driven CV outcomes trials, enrolling 2694 and 3872 patients, respectively. Major adverse CV events (MACE) were a composite of death from any cause, non-fatal myocardial infarction, and non-fatal stroke. In this post-hoc analysis, two Hb-related time-dependent covariates were constructed based on 12-weekly intervals for each patient: most recent 4-week Hb change (>1, ≥0 to ≤1, ≥-1 to <0, <-1g/dL) and most recent Hb level (low <10, medium 10 to 11.5, high >11.5 g/dL). Associations between time-varying Hb and change in Hb and risk of adjudicated first MACE were explored using a piece-wise exponential model adjusted for baseline and other covariates (Figure). Odds ratios and 95% confidence intervals are reported.


Results were consistent between daprodustat and ESA treatment arms in ASCEND-D and ASCEND-ND. A most recent 4-week Hb change >1g/dL and most recent 4-week Hb change <-1g/dL vs an Hb change ≥0 to ≤1g/dL, and low Hb vs medium Hb, were associated with higher MACE risk (Figure). No increased risk was seen with Hb changes ≥-1 to <0g/dL or with high Hb.


Our data suggest that rapid Hb changes and low absolute Hb values may be associated with higher MACE risk in patients treated with daprodustat or ESA. Additional analyses are needed to delineate these associations further.

Figure. Hb-related time-dependent covariate analyses for ASCEND-D (A) and ASCEND-ND (B)


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