Francesco Locatelli1, Thierry Hannedouche2, Steven Fishbane3, Zoe Morgan4, Delphine Oguey5, William B White6. 1. Retired from Alessandro Manzoni Hospital, ASST Lecco, Lecco, Italy; f.locatelli@asst-lecco.it. 2. School of Medicine, University of Strasbourg, Strasbourg, France. 3. Department of Medicine, Zucker School of Medicine at Hofstra/Northwell, Great Neck, New York. 4. Biostatistics, F. Hoffmann-La Roche Ltd., Basel, Switzerland. 5. Clinical Science, F. Hoffmann-La Roche Ltd., Basel, Switzerland; and. 6. Calhoun Cardiology Center, University of Connecticut School of Medicine, Farmington, Connecticut.
Abstract
BACKGROUND AND OBJECTIVES: Erythropoiesis-stimulating agents correct anemia of CKD but may increase cardiovascular risk. We compared cardiovascular outcomes and all-cause mortality associated with monthly methoxy polyethylene glycol-epoetin beta with those of the shorter-acting agents epoetin alfa/beta and darbepoetin alfa in patients with anemia of CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We conducted a multicenter, open-label, noninferiority trial in which patients were randomized to receive methoxy polyethylene glycol-epoetin beta or reference erythropoiesis-stimulating agents, stratified by maintenance or correction treatment status and C-reactive protein level. The trial had a prespecified noninferiority margin of 1.20 for the hazard ratio (HR) for the primary end point (a composite of all-cause mortality, nonfatal myocardial infarction or stroke, adjudicated by an independent blinded committee). This trial is registered with ClinicalTrials.gov, number NCT00773513. RESULTS: In total, 2818 patients underwent randomization, receivedmethoxy polyethylene glycol-epoetin beta or a reference agent, and were followed for a median of 3.4 years (maximum, 8.4 years). In the modified intention-to-treat analysis, a primary end point event occurred in 640 (45.4%) patients in the methoxy polyethylene glycol-epoetin beta arm, and 644 (45.7%) in the reference arm (HR 1.03; 95% confidence interval [95% CI], 0.93 to 1.15, P=0.004 for noninferiority). All-cause mortality was not different between treatment groups (HR 1.06; 95% CI, 0.94 to 1.19). Results in patient subgroups on dialysis or treated in the correction or maintenance settings were comparable to the primary analysis. CONCLUSIONS: In patients with anemia of CKD, once-monthly methoxy polyethylene glycol-epoetin beta was noninferior to conventional, shorter-acting erythropoiesis-stimulating agents with respect to rates of major adverse cardiovascular events or all-cause mortality.
RCT Entities:
BACKGROUND AND OBJECTIVES: Erythropoiesis-stimulating agents correct anemia of CKD but may increase cardiovascular risk. We compared cardiovascular outcomes and all-cause mortality associated with monthly methoxy polyethylene glycol-epoetinbeta with those of the shorter-acting agents epoetin alfa/beta and darbepoetin alfa in patients with anemia of CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We conducted a multicenter, open-label, noninferiority trial in which patients were randomized to receive methoxy polyethylene glycol-epoetinbeta or reference erythropoiesis-stimulating agents, stratified by maintenance or correction treatment status and C-reactive protein level. The trial had a prespecified noninferiority margin of 1.20 for the hazard ratio (HR) for the primary end point (a composite of all-cause mortality, nonfatal myocardial infarction or stroke, adjudicated by an independent blinded committee). This trial is registered with ClinicalTrials.gov, number NCT00773513. RESULTS: In total, 2818 patients underwent randomization, received methoxy polyethylene glycol-epoetinbeta or a reference agent, and were followed for a median of 3.4 years (maximum, 8.4 years). In the modified intention-to-treat analysis, a primary end point event occurred in 640 (45.4%) patients in the methoxy polyethylene glycol-epoetinbeta arm, and 644 (45.7%) in the reference arm (HR 1.03; 95% confidence interval [95% CI], 0.93 to 1.15, P=0.004 for noninferiority). All-cause mortality was not different between treatment groups (HR 1.06; 95% CI, 0.94 to 1.19). Results in patient subgroups on dialysis or treated in the correction or maintenance settings were comparable to the primary analysis. CONCLUSIONS: In patients with anemia of CKD, once-monthly methoxy polyethylene glycol-epoetinbeta was noninferior to conventional, shorter-acting erythropoiesis-stimulating agents with respect to rates of major adverse cardiovascular events or all-cause mortality.
Authors: A Levin; C R Thompson; J Ethier; E J Carlisle; S Tobe; D Mendelssohn; E Burgess; K Jindal; B Barrett; J Singer; O Djurdjev Journal: Am J Kidney Dis Date: 1999-07 Impact factor: 8.860
Authors: Francesco Locatelli; Pedro Aljama; Peter Bárány; Bernard Canaud; Fernando Carrera; Kai-Uwe Eckardt; Walter H Hörl; Iain C Macdougal; Alison Macleod; Andrzej Wiecek; Stewart Cameron Journal: Nephrol Dial Transplant Date: 2004-05 Impact factor: 5.992
Authors: Douglas S Fuller; Lindsay Zepel; Brian A Bieber; Bruce M Robinson; Ronald L Pisoni Journal: Am J Kidney Dis Date: 2015-10-31 Impact factor: 8.860
Authors: Rafael Pérez-García; Javier Varas; Alejandro Cives; Alejandro Martín-Malo; Pedro Aljama; Rosa Ramos; Julio Pascual; Stefano Stuard; Bernard Canaud; José Ignacio Merello Journal: Nephrol Dial Transplant Date: 2018-04-01 Impact factor: 5.992
Authors: Valeria M Saglimbene; Suetonia C Palmer; Marinella Ruospo; Patrizia Natale; Jonathan C Craig; Giovanni Fm Strippoli Journal: Cochrane Database Syst Rev Date: 2017-08-07
Authors: A Besarab; W K Bolton; J K Browne; J C Egrie; A R Nissenson; D M Okamoto; S J Schwab; D A Goodkin Journal: N Engl J Med Date: 1998-08-27 Impact factor: 91.245
Authors: Francesco Locatelli; Peter Bárány; Adrian Covic; Angel De Francisco; Lucia Del Vecchio; David Goldsmith; Walter Hörl; Gerard London; Raymond Vanholder; Wim Van Biesen Journal: Nephrol Dial Transplant Date: 2013-04-12 Impact factor: 5.992
Authors: Miguel G Uriol-Rivera; Aina Obrador-Mulet; Sonia Jimenez-Mendoza; Antonio Corral-Baez; Leonor Perianez-Parraga; Angel Garcia-Alvarez; Francisco J de la Prada Journal: J Hematol Date: 2021-11-29