Erythropoietin-stimulating agents (ESAs) continue to be widely prescribed despite the absence of evidence demonstrating benefit. TREAT– the first and only large trial to test clinical outcomes with the drugs–showed that ESAs did not reduce clinical events, though it did raise concerns that the drugs might increase the risk of stroke. Critics say that the drugs are still being used to treat the surrogate endpoint of hemoglobin level. Some doctors believe that ESAs can help improve the quality of life of their patients.
Now a large systematic review and meta-analysis published in Annals of Internal Medicine looks at whether ESAs might improve quality of life. Canadian researchers analyzed data from 17 studies testing either erythropoietin alfa or darbepoetin in more than 10,000 patients with chronic kidney disease. They found no significant improvements in various measures of quality-of-life, and were unable to identify a subgroup that might benefit from ESA treatment. The results were the same for hemodialysis patients and pre-dialysis patients.
Viewed with previous research in the field, the results “rule out meaningful positive effects” of the drugs on health-related quality-of-life measures, write the authors. The results might be used to support “further limitations on ESA use.” They acknowledge that it remains possible that the drugs could have significant benefits in younger patients under 40 years of age who are relatively healthy. However, they note, patients in this category “are uncommon in most North American dialysis facilities and CKD clinics.”
This is yet “another study showing the failure of surrogate outcomes,” commented Harlan Krumholz (Yale University). “Treating anemia with these expensive agents neither improves quality or quantity of life – and yet we have spent billions on them.”
Marc Pfeffer (Brigham & Women’s Hospital) was the principal investigator of TREAT, the first large randomized, placebo-controlled trial of ESAs with clinical outcomes. In an interview Pfeffer said that there is not enough placebo-controlled data to evaluate use of these drugs to improve quality of life. In the case of severely anemic patients in dialysis he said that it’s easy to see improvements when giving an ESA. The use of ESAs in this context is not considered controversial.
But for less severely anemic patients or for patients who are not on dialysis the effect on quality of life is unclear, said Pfeffer. He warned that even if a trial shows a statistically significant effect it may not be clinically significant. An additional concern is stroke, a safety signal that emerged in TREAT and received support in RED HF, an ESA trial in patients with heart failure.
Since the appearance of TREAT ESA use has been reduced. Unless they have severe anemia fewer people are starting treatment, and where it is being used doctors are not pushing the dose as high, according to Pfeffer. “Fewer people with moderate anemia are receiving it and the doses are not being pushed as high as before.”