Thilly_EU_Neuro.qxp 9/7/07 10:42 am Page 16
Anaemia Management
achieve an Hb level of 13.5g/dl or a dose targeted to achieve a level of 11g/dl, using a target Hb level of greater than 13g/dL. The control group
11.3g/dl. The median study duration was 16 months. The primary end- is administered a placebo, with Hb level allowed to decrease to 9g/dl, at
point was a composite of death, myocardial infarction, hospitalisation for which level darbepoetin alfa therapy is started.
congestive heart failure and stroke. The results recorded more events in
the high-Hb group compared with the low-Hb group (125 events versus Conclusion
97; p=0.03). However, two major limitations of this study should be Despite the results of two large RCTs,
34,35
two literature reviews
28,37
and
emphasised. First, the two groups differed at baseline in two important one meta-analysis
36
published in 2006–2007, the treatment of renal
cardiovascular characteristics: coronary artery bypass grafts (17% in the anaemia remains the focus of multiple questions and the Hb target
high-Hb group versus 14% in the low-Hb group; p=0.03); and debate is still open. CREATE and CHOIR studies have helped to focus
hypertension (95% in the high-Hb group versus 92% in the low-Hb attention on the need for large, well-conducted RCTs, but have not yet
group; p<0.02). In spite of the imbalance regarding coronary artery sufficiently answered the question of the target Hb level. Faced with this
bypass grafts and hypertension prevalence, comparisons between the controversy, what behaviour should clinicians adopt in current practice?
groups were not adjusted to take these characteristics into account. While waiting for the results of the ongoing trials, the CREATE and
Second, of the original 1,432 cohort, over half were lost in each group, CHOIR authors stated that: “taken together, these two studies suggest
thus the final numbers were closer to those in CREATE. caution in the full correction of anaemia in patients with CKD”.
38
Furthermore, costs involved in achieving normal Hb levels are extremely
One meta-analysis and one literature review on the topic, including the high; for the target of 14g/dl compared with 12–2.5g/dl, costs per
CREATE and CHOIR results, were published. In his meta-analysis,
36
quality-adjusted life-year gained is US$828,215.
39
Can we invest such
Phrommintikul et al. included nine RCTs that compared different target additional cost for a clinical benefit that remains uncertain? Probably not.
Hb concentrations in 5,143 patients both on dialysis and not on dialysis.
All-cause mortality was increased by about 20%, arteriovenous access What About Current Clinical Practice?
thrombosis by 30% and poorly controlled blood pressure by 30% in However, in current clinical practice, is the Hb level of CKD patients too
patients in the higher Hb target group compared with those in the lowest high? Are they over-treated by ESAs? Despite greater use of ESA
target group. A Cochrane library review
38
was also published at the end therapy and higher mean Hb levels over time, all epidemiological
of 2006. This review included 32 RCTs and quasi-RCTs evaluating the studies seems to show that therapeutic anaemia care remains
effects of different Hb targets in different stages on 3,707 patients both suboptimal in clinical practice.
18-27
For example, in a recent French
on dialysis and not on dialysis. The authors concluded that there was no report of 6,271 incident hemodialysis patients, 63.6% of them had an
significant difference in the risk of death for low (<12g/dl) versus higher Hb level lower than 11 g/dl and only 1% an Hb greater than 13.5g/dl
Hb targets (>13.3 g/dl). However, lower Hb targets were associated with at the dialysis initiation.
40
Off the 63.6% of patients having an Hb level
an increased risk of seizures (hazard ratio (HR) = 5.25, 95% confidence lower than 11 g/dl, 68% were not prescribed an ESA therapy. These
interval (CI) = 1.13–24.34) but a reduced risk of hypertension (HR = 0.50, results are similar in comparison with practices in different settings,
95% CI = 0.33–0.76). where this percentage ranges from 70 to 80%,
19,21,24
and confirm the
need for improvement in healthcare delivery for CKD anaemic patients.
Currently, there are several additional RCTs of complete – rather than So, how can we explain this gap between clinical practice and research
partial – correction of anaemia in patients with CKD. For example, the concerns, and what will be the impact of research results suggesting
TREAT study
37
of more than 4,000 diabetic CKD patients having an caution in anaemia correction on a clinical practice remaining
estimated GFR of 20–60ml/min started in 2005. In the intervention suboptimal? We can just hope that they will not dissuade clinicians
group, darbepoetin alfa is prescribed to patients with an Hb less than from prescribing ESAs to CKD patients. ■
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16 EUROPEAN RENAL DISEASE 2007
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