Wolfgang C Winkelmayer1, Tara I Chang2, Aya A Mitani3, Emilee R Wilhelm-Leen2, Victoria Ding3, Glenn M Chertow2, M Alan Brookhart4, Benjamin A Goldstein5. 1. Section of Nephrology, Baylor College of Medicine, Houston, TX; Division of Nephrology, Department of Medicine; Stanford University School of Medicine, Palo Alto, CA. Electronic address: winkelma@bcm.edu. 2. Division of Nephrology, Department of Medicine; Stanford University School of Medicine, Palo Alto, CA. 3. Division of General Medical Disciplines, Department of Medicine; Stanford University School of Medicine, Palo Alto, CA. 4. Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC. 5. Division of General Medical Disciplines, Department of Medicine; Stanford University School of Medicine, Palo Alto, CA; Duke University School of Medicine, Durham, NC.
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 therapy in facilities (almost) exclusively using DPO versus EPO. SETTING & PARTICIPANTS: Nonchain US hemodialysis facilities; each facility switching from EPO to DPO (2003-2010) was matched for location, profit status, and facility type with one EPO facility. Patients subsequently initiating hemodialysis therapy in these facilities were assigned their facility-level exposure. INTERVENTION: DPO versus EPO. OUTCOMES: All-cause mortality, cardiovascular mortality; composite of cardiovascular death, nonfatal myocardial infarction (MI), and nonfatal 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: 9,465 [47.5%]; EPO: 10,467 [52.5%]) incident hemodialysis patients were followed up for 21,918 person-years during which 5,550 deaths occurred. Almost all baseline characteristics were tightly balanced. The demographics-adjusted mortality HR for DPO (vs EPO) was 1.06 (95% CI, 1.00-1.13) and was 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). Nonfatal outcomes were evaluated among 9,455 patients with fee-for-service Medicare: 4,542 (48.0%) in DPO and 4,913 (52.0%) in EPO facilities. During 10,457 and 10,363 person-years, 248 and 372 events were recorded, respectively, for strokes and MIs. 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: Nonrandom treatment assignment, potential residual confounding. CONCLUSIONS: In incident hemodialysis patients, mortality and cardiovascular event rates did not differ between patients treated at facilities predominantly using DPO versus EPO.
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 therapy in facilities (almost) exclusively using DPO versus EPO. SETTING & PARTICIPANTS: Nonchain US hemodialysis facilities; each facility switching from EPO to DPO (2003-2010) was matched for location, profit status, and facility type with one EPO facility. Patients subsequently initiating hemodialysis therapy in these facilities were assigned their facility-level exposure. INTERVENTION: DPO versus EPO. OUTCOMES: All-cause mortality, cardiovascular mortality; composite of cardiovascular death, nonfatal myocardial infarction (MI), and nonfatal 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: 9,465 [47.5%]; EPO: 10,467 [52.5%]) incident hemodialysis patients were followed up for 21,918 person-years during which 5,550 deaths occurred. Almost all baseline characteristics were tightly balanced. The demographics-adjusted mortality HR for DPO (vs EPO) was 1.06 (95% CI, 1.00-1.13) and was 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). Nonfatal outcomes were evaluated among 9,455 patients with fee-for-service Medicare: 4,542 (48.0%) in DPO and 4,913 (52.0%) in EPO facilities. During 10,457 and 10,363 person-years, 248 and 372 events were recorded, respectively, for strokes and MIs. 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: Nonrandom treatment assignment, potential residual confounding. CONCLUSIONS: In incident hemodialysis patients, mortality and cardiovascular event rates did not differ between patients treated at facilities predominantly using DPO versus EPO.
Authors: Yves Vanrenterghem; Peter Bárány; Johannes F E Mann; Peter G Kerr; Janet Wilson; Nigel F Baker; Stephen J Gray Journal: Kidney Int Date: 2002-12 Impact factor: 10.612
Authors: Allen R Nissenson; Suzanne K Swan; Jill S Lindberg; Steven D Soroka; Robert Beatey; Chao Wang; Nancy Picarello; Anna McDermott-Vitak; Bradley J Maroni Journal: Am J Kidney Dis Date: 2002-07 Impact factor: 8.860
Authors: Ferdinand H Bahlmann; Kirsten DeGroot; Thorsten Duckert; Eva Niemczyk; Elisabeth Bahlmann; Sascha M Boehm; Hermann Haller; Danilo Fliser Journal: Kidney Int Date: 2003-11 Impact factor: 10.612
Authors: Medha Airy; Sreedhar Mandayam; Aya A Mitani; Tara I Chang; Victoria Y Ding; M Alan Brookhart; Benjamin A Goldstein; Wolfgang C Winkelmayer Journal: Nephrol Dial Transplant Date: 2015-08-26 Impact factor: 5.992
Authors: Wolfgang C Winkelmayer; Benjamin A Goldstein; Aya A Mitani; Victoria Y Ding; Medha Airy; Sreedhar Mandayam; Tara I Chang; M Alan Brookhart; Steven Fishbane Journal: Am J Kidney Dis Date: 2017-01-04 Impact factor: 8.860