NEW YORK (Reuters Health) – In patients with chronic kidney disease (CKD) and anemia, targeting higher hemoglobin levels with an erythropoietic agent is not helpful and is very likely harmful, according to an updated meta-analysis published online May 3 in Annals of Internal Medicine.
“Evidence for harm when targeting higher hemoglobin values in CKD has now been available for more than 20 years” and should be incorporated into clinical practice, Dr. Suetonia C. Palmer from University of Otago, Christchurch, New Zealand and colleagues conclude.
In a previous meta-analysis, pooled data from 9 randomized controlled trials and 5143 CKD patients with anemia suggested that higher hemoglobin targets increased the risk of arteriovenous access thrombosis and hypertension, and death from any cause, compared to lower targets.
Dr. Palmer and colleagues updated that meta-analysis to include 27 trials with 10,452 participants. The trials compared erythropoietic agents (erythropoietin-alfa or -beta, or darbepoetin) to placebo, no treatment, or a different erythropoiesis-stimulating medication, for achieving various hemoglobin targets.
The researchers say the high-target ranges shifted upward over time. Before 1998, the higher target range was generally 95 to 120 g/L. From 1998 to 2008, however, studies used higher target ranges between 120 and 150 g/L, with lower targets between 90 and 120 g/L – in the range considered “higher” in the earlier trials.
Overall, the median hemoglobin level achieved by treatment was 130 g/L in the high target groups (interquartile range, 120 to 140) and 101 g/L in the low target groups (IQR, 92 to 110).
Patients in the higher target groups had higher relative risks for stroke (RR, 1.51), hypertension (RR, 1.67), and vascular access thrombosis (RR, 1.33) compared to patients in the low target groups.
Targeting a higher hemoglobin level made no difference to the relative risks for all-cause mortality (RR, 1.09), serious cardiovascular events (RR, 1.15), or end-stage kidney disease (RR, 1.08), “although point estimates favored a lower hemoglobin target,” the authors report.
The results were consistent across subgroups, including all stages of CKD, the authors note.
Patients in the high-target groups had a reduced need for red blood cell transfusions, but they also had a greater need for intravenous iron therapy. There was no suggestion of any “clinically important” effects of ESA therapy quality of life.
Cancer patients with anemia also have higher mortality with higher hemoglobin targets, according to the researchers.
The National Kidney Foundation clinical practice guideline for anemia in chronic kidney disease advises a hemoglobin target of 110 to 120 g/L – but “the rationale…is unclear,” Dr. Palmer and colleagues conclude.
Ann Intern Med 2010.