Evaluating Darbepoetin Treatment Strategies for Managing Anaemia in Haemodialysis Patients: Effects on All‐Cause Mortality From a Target Trial Emulation Using Electronic Health Record Data

ABSTRACT Purpose Anaemia is a common complication of chronic kidney disease, often treated with erythropoiesis‐stimulating agents (ESAs), but the optimal haemoglobin (Hb) target remains uncertain. Using electronic health records, we emulated a target trial comparing different Hb targets in haemodialysis patients to estimate their effects on mortality. Methods We used electronic health records from UK kidney centres reporting to the UK Renal Registry. Adults aged ≥ 18 years, receiving haemodialysis for ≥ 3 months, and without marked ESA resistance were eligible. Using the clone‐censor‐weight method, we emulated trials comparing Hb targets: (1) 105–125 versus 95–115 g/L and (2) 125–145 versus 95–115 g/L. Darbepoetin dosing followed a standardised protocol with predefined dose adjustments and a maximum dose of 150 μg/week. The outcome was all‐cause mortality over 8 months. Results The study included 8628 patients from 10 centres between 2004 and 2016; 62% male, median age 66 years (IQR 52–76). At baseline, mean Hb was 97.7 g/L (SD 15.1), and 79% of patients were receiving darbepoetin. The hazard ratio for mortality was 0.92 (95% CI 0.75–1.12) for the 105–125 versus 95–115 g/L comparison, and 1.20 (95% CI 0.94–1.54) for the 125–145 versus 95–115 g/L comparison. Adherence to the highest Hb target was lower, limiting precision. Conclusions Targeting an Hb range of 105–125 g/L under controlled ESA dosing was not associated with increased mortality compared with 95–115 g/L. Targeting Hb levels above 125 g/L may increase mortality risk, consistent with previous trial findings.