Normalization of haemoglobin: why not?

It has been suggested that normalization of haemoglobin with epoetin in anaemic chronic renal failure (CRF) patients might result in even greater benefits than those currently achieved with partial haemoglobin correction. Four prospective randomized trials recently examined this hypothesis. The Scandinavian Multicentre Trial, which was completed in February 1998, included 416 haemodialysis, continuous ambulatory peritoneal dialysis and predialysis patients. Preliminary analysis of the data found no differences with respect to safety between patients treated to achieve subnormal haemoglobin (9.0-12.0 g/dl) and those in whom haemoglobin was normalized (13.5-16.0 g/dl). The Canadian Multicentre Trial included 159 haemodialysis patients with asymptomatic left ventricular (LV) dysfunction. In patients with a normal LV cavity volume at enrolment, the change in LV cavity volume at 48 weeks was significantly greater in the control group (target haemoglobin 9.5-10.5 g/dl) than in the intervention group (target haemoglobin 13.0-14.0 g/dl). The Normal Hematocrit Cardiac Trial in the US included 1233 haemodialysis patients with clinically evident ischaemic heart disease or congestive heart failure. The trial was stopped in 1996 after an interim analysis showed increased mortality in the intervention group (target haematocrit 42%) compared with the control group (target haematocrit 30%). The higher haematocrit values themselves, however, did not appear to be responsible for the differences in mortality, as the mortality rates within each group decreased with increasing haematocrit. Nonetheless, until evidence is available from other trials demonstrating a benefit of normalizing haemoglobin, it has been recommended that a target haematocrit value of 42% be avoided in haemodialysis patients with clinically evident ischaemic heart disease or congestive heart failure. Further studies are also required to determine whether increasing haemoglobin to normal may prove to be beneficial in other patient groups. The Spanish Quality of Life Study of 134 haemodialysis patients found a significant improvement in all quality-of-life parameters when haemoglobin was increased to a mean of 12.5 g/dl. The investigators suggested that in patients without severe co-morbidity, the target haemoglobin should be as close to normal as possible.