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Previous Volume 355:2071-2084 November 16, 2006 Number 20 Next

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ABSTRACT

Background Whether correction of anemia in patients with stage 3 or 4 chronic kidney disease improves cardiovascular outcomes is not established.

Methods We randomly assigned 603 patients with an estimated glomerular filtration rate (GFR) of 15.0 to 35.0 ml per minute per 1.73 m² of body-surface area and mild-to-moderate anemia (hemoglobin level, 11.0 to 12.5 g per deciliter) to a target hemoglobin value in the normal range (13.0 to 15.0 g per deciliter, group 1) or the subnormal range (10.5 to 11.5 g per deciliter, group 2). Subcutaneous erythropoietin (epoetin beta) was initiated at randomization (group 1) or only after the hemoglobin level fell below 10.5 g per deciliter (group 2). The primary end point was a composite of eight cardiovascular events; secondary end points included left ventricular mass index, quality-of-life scores, and the progression of chronic kidney disease.

Results During the 3-year study, complete correction of anemia did not affect the likelihood of a first cardiovascular event (58 events in group 1 vs. 47 events in group 2; hazard ratio, 0.78; 95% confidence interval, 0.53 to 1.14; P=0.20). Left ventricular mass index remained stable in both groups. The mean estimated GFR was 24.9 ml per minute in group 1 and 24.2 ml per minute in group 2 at baseline and decreased by 3.6 and 3.1 ml per minute per year, respectively (P=0.40). Dialysis was required in more patients in group 1 than in group 2 (127 vs. 111, P=0.03). General health and physical function improved significantly (P=0.003 and P<0.001, respectively, in group 1, as compared with group 2). There was no significant difference in the combined incidence of adverse events between the two groups, but hypertensive episodes and headaches were more prevalent in group 1.

Conclusions In patients with chronic kidney disease, early complete correction of anemia does not reduce the risk of cardiovascular events. (ClinicalTrials.gov number, NCT00321919 [ClinicalTrials.gov] .)

Source Information

From Inserm Unité 507 and Assistance Publique–Hôpitaux de Paris, Necker Hospital, Division of Nephrology, Paris (T.B.D.); the Department of Nephrology and Dialysis, Ospedale A. Manzoni, Lecco, Italy (F.L.); the Department of Nephrology, University Hospital Lund, Lund, Sweden (N.C.); the Department of Nephrology and Hypertension, University of Erlangen-Nürnberg, Erlangen, Germany, and the First Medical Clinic, Mannheim University Hospital, University of Heidelberg, Heidelberg, Germany (K.-U.E.); the Department of Renal Medicine, King's College Hospital, London (I.C.M.); the Department of Nephrology, General Hospital of Veria, Veria, Greece (D.T.); and the Pharmaceutical Division, F. Hoffmann–La Roche, Basel, Switzerland (H.-U.B., A.S.).

Address reprint requests to Dr. Drüeke at Unité 507 de l'INSERM and Service de Néphrologie, Hôpital Necker, Université Paris-V, Paris, France, or at drueke{at}necker.fr.

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