#5749 rates of selected cardiovascular and non-cardiovascular events among dialysis patients with anemia in the us medicare population

Abstract Background and Aims The safety and efficacy of daprodustat in patients on dialysis were reported in ASCEND-D/ID trials [1,2]. Trials impose strict criteria for enrollment, making participants more narrowly selected than a broader population with disease who might benefit from treatment. We describe events, of which most were noted as safety events in ASCEND-D/ID trials, among general anemia “treatment eligible” (TE) patients on dialysis and patients similar to those in ASCEND-D/ID trials (“clinical trial-like” [CTL]) in the US. Method Using United States Renal Data System data, we conducted a retrospective cohort study of incident dialysis-dependent (IDD) patients from 2017–2019 and, separately, point prevalent dialysis-dependent (PDD) patients as of Jan 1 2018. Dialysis initiation date was the index date for IDD patients and Jan 1 2018 for PDD patients. We also required patients to have ≥6 months of continuous Medicare coverage before, and be aged ≥18 years on, index date. Patients with a history of kidney transplant or who had cancer during the year prior, and those who had a hospitalization for heart failure (HF), myocardial infarction (MI), or stroke in the 4 weeks before, the index date were excluded. For IDD patients, we required use of ESAs at the index date to support comparability to the PDD patients. The CTL cohort was a subset of the TE cohort, approximating eligibility in the ASCEND-D/ID trials. Patients were followed from index date to the earliest date of death, loss of Medicare coverage, kidney transplantation, or Dec 31 2019. We assessed cardiovascular (CV: all-cause death, HF, MI, stroke, thromboembolic events [TEEs], major cardiovascular events [MACE: death, MI, stroke] and MACE+HF) and non-CV (cancer, gastric erosions, ocular events, seizures, serious infections) events, derived from medical claims in the follow-up period using ICD-10 diagnosis, Healthcare Common Procedure Coding System, and Current Procedural Terminology codes. HF, MI, stroke, and serious infections were defined as inpatient events. First event rates for TE and CTL cohorts were calculated separately for IDD and PDD patients and expressed as number of events per 100 patient-years (PYs). Results Of IDD patients, 23,909 were in the TE and 6,962 in the CTL cohorts; corresponding numbers were 230,055 and 41,980 for PDD patients. Median follow-up was 12.6 and 13.8 months for the TE and CTL cohorts, respectively, in IDD patients; and 24 months for both TE and CTL cohorts in PDD patients. Mean ages were 70.3 and 71.0 years for the TE and CTL cohorts in IDD patients; and 63.3 and 64.1 years for the TE and CTL cohorts in PDD patients. For both IDD and PDD patients, the TE and CTL cohorts had similar demographics, but the TE cohorts had a slightly higher proportion of patients with comorbidities. First event rates are shown in the Table. TE cohorts had higher rates than CTL cohorts for most CV events (mortality, 17.3 vs 14.0 per 100 PYs in IDD and 16.8 vs 15.1 in PDD; MACE; 20.9 vs 17.5 in IDD and 20.3 vs 18.6 in PDD; MACE+HF, 25.6 vs 21.8 in IDD, 26.9 vs 25.1 in PDD). In IDD patients, HF was more common in the TE than the CTL cohort (7.1 vs 6.1) but was similar in PDD patients. MI, stroke, and TEEs (vascular access thrombosis [in hemodialysis patients only], deep venous thrombosis, and pulmonary embolism) had similar rates in the TE and CTL cohorts for both IDD and PDD patients. Serious infections were higher in the TE than the CTL cohort in both IDD and PDD patients. In PDD patients, gastric erosions were higher in the TE than the CTL cohort (40.0 vs 38.5) while ocular events and retinal hemorrhage were lower in the TE cohort. Conclusion Rates for most CV events were higher in TE cohorts, comprised of patients eligible for anemia treatment, compared with CTL cohorts mimicking trial participants. Rates of non-CV events did not show a consistent pattern. As expected, rates of VAT were higher in IDD than PDD patients. These findings further contextualize real-world event rates of interest in dialysis populations. Reported rates were crude (unadjusted) and should be interpreted with caution. Funding: GSK (study 217316).