A threshold trajectory was revealed by isolating the effects of hemoglobin rate of rise in anemia of chronic kidney disease

Gregory Fusco; Ali Hariri; Carlos Vallarino; Ajay Singh; Peter Yu; Lesley Wise

doi:10.1177/2042098617716819

A threshold trajectory was revealed by isolating the effects of hemoglobin rate of rise in anemia of chronic kidney disease

Ther Adv Drug Saf. 2017 Oct;8(10):305-318. doi: 10.1177/2042098617716819. Epub 2017 Jul 12.

Authors

Gregory Fusco¹, Ali Hariri², Carlos Vallarino³, Ajay Singh⁴, Peter Yu³, Lesley Wise⁵

Affiliations

¹ Epividian, Inc., 4819 Emperor Boulevard, Suite 400, Durham, NC 27703, USA.
² Sanofi Pharmaceuticals, Inc., Bridgewater, NJ, USA.
³ Takeda Pharmaceuticals International Inc., Deerfield IL, USA.
⁴ Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
⁵ Wise Pharmacovigilance and Risk Management, Ltd., UK.

Abstract

Background: To assess cardiovascular risk among various hemoglobin (Hb) rates of rise (RoR) in chronic kidney disease (CKD) patients with anemia who have initiated therapy with erythropoiesis stimulating agents (ESAs).

Methods: Observational cohort of CKD patients initiating ESA therapy from the Centricity^® database, 1990-2011. Proportional hazards models tested the hypothesis that a slower Hb RoR (0 < g/dl/month ⩽ 0.125) is associated with a lower cardiovascular (CV) incidence [composite of fatal/nonfatal myocardial infarction (MI) and stroke] compared with faster RoR (0.125 < g/dl/month ⩽ 2.0, and >2.0 g/dl/month).

Results: A total of 9220 patients receiving ESAs were followed for an average of 3.1 years. Slow (group B) RoR versus medium (group C') and fast (group D') RoR in Hb, throughout all Hb milestones, was associated with lower risk of the composite endpoint [B (slow) versus D' (fast) [hazard ratio (HR) = 0.20 (0.11, 0.39), p < 0.0001]; B versus C' (medium) [HR = 0.34 (0.19, 0.62), p = 0.0004], and C' versus D' [HR = 0.60 (0.42, 0.85), p = 0.005]]. Within achieved Hb milestones, HRs were: B versus D' at milestone ⩾ 14.1 g/dl [HR = 0.17 (0.05, 0.56); p = 0.004] and at milestone 12.6-14.0 [HR = 0.18 (0.07, 0.46), p = 0.0004].

Conclusion: Rapid Hb rise is associated with adverse CV outcomes, with markedly lower risk for rates below a threshold trajectory of 0.125 g/dl/month, even with complete correction.

Keywords: chronic kidney disease anemia; erythropoiesis stimulating agents; hemoglobin rate of rise; hemoglobin reconstitution; hyporesponsiveness; management of; threshold trajectory.