High-Dose IV Iron Anemia Therapy Safe in Hemodialysis

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Randomized controlled trial finds no significant difference between high- and low-dose intravenous iron with respect to mortality, non-fatal cardiovascular outcomes, and infection.
Randomized controlled trial finds no significant difference between high- and low-dose intravenous iron with respect to mortality, non-fatal cardiovascular outcomes, and infection.
The following article is part of conference coverage from Kidney Week 2018 in San Diego hosted by the American Society of Nephrology. Renal & Urology News staff will be reporting live on medical studies conducted by nephrologists and other specialists who are tops in their field in acute kidney injury, chronic kidney disease, dialysis, transplantation, and more. Check back for the latest news from Kidney Week 2018.

SAN DIEGO—Administering higher doses of intravenous (IV) iron to manage anemia in patients on hemodialysis significantly reduces dose requirements of erythropoiesis-stimulating agents (ESAs) without increasing the risk of death or hospitalization for infection or any other cause, according to study findings presented at the American Society of Nephrology's Kidney Week 2018 conference and published online concurrently in the New England Journal of Medicine.

In the multicenter, controlled PIVOTAL Trial, Iain C. Macdougall, MBChB, MD, of King's College Hospital in London, and colleagues randomly assigned 2141 patients who had been on hemodialysis (HD) for less than 1 year to receive either a reactive low-dose IV iron regimen or a proactive high-dose IV iron regimen.

In the reactive group, patients received low-dose iron sucrose if ferritin levels dropped below 200 µg/dL and/or transferrin saturation (TSAT) decreased below 20%. The proactive group received iron sucrose 400 mg monthly unless ferritin levels were above 700 µg/dL and/or TSAT levels were 40% or above. The primary study outcome of interest was a composite of non-fatal myocardial infarction, non-fatal stroke, hospitalization for heart failure, or death.

Patients had a median 2.1 years of follow-up. The incidence of the primary outcome was numerically lower in the high-dose than low-dose study arm (30.5% vs 32.7%). In adjusted analyses, the high-dose group had a 12% decreased risk of the primary outcome, which was significant for non-inferiority but not superiority.

In addition, the high- and low-dose groups showed no significant differences in the incidence of all-cause mortality (22.5% vs. 25.7%), all-cause hospitalization (59.6% vs 58.8%), and hospitalization for infection (29.6% vs. 29.3%). The median ESA dose was 19.7% lower in the high-dose compared with the low-dose iron group.

During a press conference at which the study findings were presented, co-investigator David C. Wheeler, MBChB, MD, University College London, noted that the reduction in ESA requirements “may be good if ESAs promote cardiovascular events.”

Observational data have suggested that patients receiving higher doses of iron are at higher risk of infection and death from infection, and in vitro studies provide evidence that iron promotes bacterial growth and inhibits the body's immune reaction to bacterial infection, Dr Wheeler said. Observational and experimental data, however, are often biased by confounding factors. The findings from the PIVOTAL Trial show that the observational and experimental data do not “stack up in real life,” Dr Wheeler said. “The best test is a randomized controlled trial, which showed no difference in infection.”


Visit Renal & Urology News' conference section for continuous coverage from Kidney Week 2018.


Reference

Macdougall IC, White C, Anker SD, et al. High-dose versus low-dose intravenous iron therapy in hemodialysis: The PIVOTAL Trial. Presented at the American Society of Nephrology's Kidney Week 2018 conference in San Diego, Oct. 23-28. Abstract FR-OR143.

Macdougall IC, White C, Anker SD, et al, for the PIVOTAL Investigators and Committees.  Intravenous iron in patients undergoing maintenance hemodialysis. N Engl J Med. 2018; published online ahead of print.

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