Abstract: FR-OR145
Cardiovascular Safety of Methoxy Polyethylene Glycol-Epoetin Beta in Treatment of Anemia of CKD
Session Information
- High-Impact Clinical Trials
October 26, 2018 | Location: 20A, San Diego Convention Center
Abstract Time: 11:15 AM - 11:30 AM
Category: Anemia and Iron Metabolism
- No subcategory defined
Authors
- Locatelli, Francesco, Alessandro Manzoni Hospital, ASST Lecco, Lecco, Italy
- Hannedouche, Thierry P., University of Strasbourg School of Medicine, Strasbourg, France
- Fishbane, Steven, North Shore University Hospital, New York, New York, United States
- Morgan, Zoe, F. Hoffmann-La Roche Ltd, Basel, Switzerland
- Oguey, Delphine, F. Hoffmann-La Roche Ltd, Basel, Switzerland
- White, William B., University of Connecticut School of Medicine, Farmington, Connecticut, United States
Background
Erythropoiesis-stimulating agents (ESAs) may increase the risk of cardiovascular events when used in the treatment of anemia of CKD. We compared cardiovascular outcomes and all-cause mortality for monthly methoxy polyethylene glycol-epoetin beta (continuous erythropoietin receptor activator, C.E.R.A.) with those of reference ESAs epoetin alfa/beta and darbepoetin alfa in the MIRCERA Post-Approval Safety Study (PASS).
Methods
MIRCERA PASS was a prospective, multicenter, open-label, blinded endpoints, non-inferiority trial. CKD patients with anemia were randomized either to start or switch to C.E.R.A., or to a reference ESA for correction or in the maintenance setting. The primary endpoint was the composite of all-cause mortality and non-fatal myocardial infarction or stroke, adjudicated by an independent committee unaware of treatment assignment. Non-inferiority was defined as the two-sided 95% confidence interval (CI) upper boundary of the hazard ratio [HR] <1.2.
Results
2825 patients were randomized between December 2008 and November 2011 and 2818 were treated for a median of 3.4 years (maximum 8.5 years). The primary endpoint occurred in 640/1409 patients (45.4%) in the C.E.R.A. arm and 644/1409 (45.7%) in the reference ESAs arm (HR 1.03; 95% CI, 0.93–1.15; p=0.0039 for non-inferiority). Subgroup analyses showed no significant differences between treatment groups for patients on dialysis or not, those with or without diabetes, or in the maintenance or correction setting. Similar findings were seen for individual components of the primary endpoint, all-cause mortality (HR 1.06, 95% CI 0.94–1.19), and non-fatal myocardial infarction or stroke (HR 0.91, 95% CI 0.74–1.12). Mean hemoglobin was maintained at 10–12 g/dL throughout the trial and was comparable between treatment arms, as were serum iron parameters. Gastrointestinal bleeding and thromboembolic events were also similar between treatment groups. No patient developed antibody-mediated pure red cell aplasia.
Conclusion
In patients with anemia of CKD, long-term treatment with monthly C.E.R.A. resulted in overall rates of major cardiovascular events and all-cause mortality similar to those associated with reference ESAs administered more frequently. Study registered at clinicaltrials.gov (NCT00773513).
Funding
- Commercial Support – F Hoffmann-La Roche Ltd