POS-288 THE BURDEN OF HEART FAILURE IN PATIENTS WITH NON–DIALYSIS-DEPENDENT ANAEMIA OF CHRONIC KIDNEY DISEASE RECEIVING ERYTHROPOIESIS-STIMULATING AGENTS: A SYSTEMATIC LITERATURE REVIEW

Abstract

Anaemia of chronic kidney disease (CKD) is associated with significant morbidity and increased mortality, particularly cardiovascular complications such as heart failure (HF). We performed a systematic literature review of the treatment options for anaemia of CKD in non-dialysis-dependent (NDD) patients. This abstract reports HF-related outcomes from clinical trials in patients with NDD anaemia of CKD. We identified randomised controlled trials (RCTs; phase 2+) for erythropoiesis-stimulating agents (ESAs) for the treatment of anaemia of CKD in adults, from electronic databases (Embase®, MEDLINE®, Cochrane library), grey literature and other sources. Outcomes were not used in the search to avoid excluding eligible trials. Other criteria were, English publications between database inception and 23 January 2020 (search date). Risk of bias was assessed using a quality appraisal checklist. Descriptive statistics assessed study and patient characteristics and HF-related outcomes in ESA trials. A total of 4,024 abstracts were screened and 325 full-text publications reviewed; 38 ESA RCTs that randomised 12,594 patients with NDD-CKD and anaemia met the inclusion criteria. Mean age range was 46.0–84.4 years; median study duration was 50.5 weeks. Most trials (24; 63%) were open-label; 9 (24%) were double-blind. Twenty-seven trials were determined to have a risk of bias but remained in the descriptive assessment. Comparative trials most often investigated darbepoetin alfa or its biosimilar (DPO; 12 trials), epoetin alfa (EPO A) or its biosimilar and recombinant human erythropoietin (16 trials) and continuous erythropoietin receptor activator (3 trials). HF-related outcomes were reported in 19 trials, including as the primary endpoint in 7 trials. HF occurrence as an adverse event (AE; 15 trials), change in left ventricular mass index (LVMI; 7 trials), and hospitalisation related to HF (1 trial) were reported. Heterogeneity in outcome definitions and reporting was observed. One trial comparing a low haemoglobin (Hb) target (9.0–11.0 g/dL) with low dose ESA vs. a high Hb target (11.0–13.0 g/dL) with DPO reported significant LVMI reduction from baseline in the high Hb group (−7.8 g/m2; 95% CI: −12.1 to −3.6 g/m2; P<0.001). Another study reported a significantly reduced LVMI (P=0.02) with EPO A (−5.7±14.2 g/m2) and DPO (−5.6±15.8 g/m2) vs. controls (no ESA); however, no difference in LVMI decrease was observed between treatment arms. One study included hospitalisation for congestive HF without renal replacement therapy as a component of the composite primary endpoint. Of the 222 composite events, 101 (45.5%) hospitalisations for congestive HF were reported in the high and low Hb EPO A treatment arms combined. The proportions of patients from the safety populations (n=13,082) with a congestive HF AE ranged from 0% to 9.0% across trials and treatment arms. Findings of this review suggested a potentially high occurrence of HF-related outcomes, such as LVMI reduction and hospitalisations. We observed substantial heterogeneity in the reporting and results of HF-related outcomes in ESA RCTs. Information from observational studies may also be needed to fully characterise the burden of HF in patients with NDD-CKD and anaemia on ESA treatment.