3807 HEART FAILURE IN ASCEND-ND AND ASCEND-D

Abstract Background and Aims Heart failure (HF) is a common cardiovascular (CV) complication in chronic kidney disease (CKD) [1]. Two CV outcome trials (ASCEND-ND [NCT02876835][2] and ASCEND-D [NCT02879305][3]) have provided the principal assessment of CV risk with daprodustat in CKD: both studies showed noninferiority of daprodustat to erythropoiesis-stimulating agent (ESA). Here, we examined the risk of HF in daprodustat-treated patients in the ASCEND-ND and ASCEND-D trials. Method The Phase 3, open-label, randomised, event-driven ASCEND trials investigated oral, once-daily daprodustat vs injectable ESA in patients with anaemia of CKD not on (ASCEND-ND) or on (ASCEND-D) dialysis. Time-to-first adjudicated major adverse CV event (MACE) was the primary CV endpoint. Time-to-first MACE or hospitalisation for heart failure (HHF) was a key secondary endpoint; the composite of time-to-first adjudicated MACE + HHF was assessed as a principal secondary endpoint, and time-to-first HHF alone as an additional secondary endpoint. To better understand HF-specific outcomes, post-hoc analyses accounting for competing risk of death were conducted via the composite endpoint of all-cause mortality (ACM) + HHF – more typically employed to evaluate HF-specific outcomes and to assess “hospitalisation-free survival”. Post-hoc subgroup analyses of patients identified as having a baseline HF history were also conducted. Results Overall, 3872 and 2964 patients were randomised in ASCEND-ND and ASCEND-D, respectively. All key prespecified and post-hoc CV endpoints in ASCEND-ND and ASCEND-D are shown in the Table, and the composite endpoint of ACM + HHF is shown in the Figure. In summary, for components of MACE for daprodustat vs ESA, respectively, ACM events were similar between treatment arms in both studies: ASCEND ND: 11.6% vs 12.2%; ASCEND-D: 14.8% vs 14.6%. For HHF alone in both studies, event rates for daprodustat vs ESA, respectively, were: 7.2% vs 5.9% (hazard ratio [HR] 95% confidence interval [CI] = 1.22 [0.95, 1.56]) in ASCEND ND; and 7.5% vs 6.8% (HR [95% CI] = 1.10 [0.84, 1.45]) in ASCEND-D. In post-hoc analyses using the composite endpoint of ACM + HHF in ASCEND-ND, the event rate for daprodustat was 20.3% (n = 393/1937), and the event rate for ESA was 19.0% (n = 368/1935) (HR [95% CI] = 1.09 [0.94, 1.26]). More HHF events were observed in patients with a history of HF (daprodustat: 20.4% [n = 54/265]; ESA: 13.4% [n = 34/254]). In ASCEND-D, ACM + HHF events were simil