Longer-term Outcomes of Darbepoetin Alfa Versus Epoetin Alfa in Patients With ESRD Initiating Hemodialysis: A Quasi-experimental Cohort Study

Abstract

Background Adequately-powered studies directly comparing hard clinical outcomes of darbepoetin alfa (DPO) versus epoetin alfa (EPO) in patients undergoing dialysis are lacking. Study Design Observational, registry-based, retrospective cohort study; we mimicked a cluster-randomized trial by comparing mortality and cardiovascular events in US patients initiating hemodialysis in facilities (almost) exclusively using DPO versus EPO. Setting & Participants Non-chain US hemodialysis facilities; each facility switching from EPO to DPO (2003–2010) was matched on location, profit status, and facility type with one EPO facility. Patients subsequently initiating hemodialysis in these facilities were assigned their facility-level exposure. Intervention DPO versus EPO. Outcomes All-cause mortality, cardiovascular mortality; composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Measurements Unadjusted and adjusted HRs from Cox proportional hazards regression models. Results Of 508 dialysis facilities that switched to DPO, 492 were matched with a similar EPO facility; 19,932 (DPO: 9465 [47.5%]; EPO: 10,467 [52.5%]) incident hemodialysis patients were followed up for 21,918 person-years during which 5550 deaths occurred. Almost all baseline characteristics were tightly balanced. The demographics-adjusted mortality HR for DPO (versus EPO) was 1.06 (95% CI, 1.00–1.13) and remained materially unchanged after adjustment for all other baseline characteristics (HR, 1.05; 95% CI, 0.99–1.12). Cardiovascular mortality did not differ between groups (HR, 1.05; 95% CI, 0.94–1.16). Non-fatal outcomes were evaluated among 9455 patients with fee-for-service Medicare: 4542 (48.0%) in DPO and 4913 (52.0%) in EPO facilities. Over 10,427 and 10,335 person-years, 246 strokes and 370 MIs were recorded, respectively. We found no differences in adjusted stroke or MI rates, or their composite with cardiovascular death (HR, 1.10; 95% CI, 0.96–1.25). Limitations Non-random treatment assignment, potential residual confounding. Conclusions In incident hemodialysis patients, mortality and cardiovascular event rates did not differ among patients treated at facilities predominantly using DPO versus EPO.

Comparative outcomes of predominant facility-level use of ferumoxytol versus other intravenous iron formulations in incident hemodialysis patients

“…Specifically, we used administrative data to mimic a cluster-randomized design, with clustering based on facility by assigning facilities and their incident hemodialysis patients to a treatment arm based on the predominant practice pattern of their facility. We have recently applied this design in a comparative safety study among erythropoiesis-stimulating agents [8].…”

Patterns of Erythropoiesis-Stimulating Agent Use in European Hemodialysis Patients: The Dialysis Outcomes and Practice Patterns Study

“…To wit, we observed that nearly 70% of European facilities use more than 1 ESA type, and nearly 30% use 3 or more. Comparative studies of established ESA products have generally been unable to detect substantial differences in efficacy or safety outcomes [11][12][13]. The decision to use 1 ESA over another can thus be summarized by several other factors: chiefly cost, availability, and preferences for dosing fre- quency [14].…”

Safety of Intravenous Iron in Hemodialysis: Longer-term Comparisons of Iron Sucrose Versus Sodium Ferric Gluconate Complex

“…We have recently used this design in two comparative safety studies of erythropoiesis-stimulating agents and of ferumoxytol, and the following resembles the methods described therein. (8, 9) This approach is particularly attractive for the intermittent nature of iron treatment, where iron storage parameters and (temporary and sometimes relative) contraindications will lead to potentially strong, and partly unobserved, time-dependent confounding that may be difficult to accommodate using traditional or novel (marginal-structural models) methods for time-dependent exposures.…”