Proactive, high-dose intravenous iron reduces mortality and major cardiovascular events in hemodialysis patients, reports a randomized trial in The New England Journal of Medicine.
The Proactive IV Iron Therapy in Dialysis Patients (PIVOTAL) trial included 2141 adults undergoing maintenance hemodialysis and receiving an erythropoiesis-stimulating agent (ESA) at 50 UK sites. One group was assigned to a proactive high-dose iron strategy: iron sucrose 400 mg IV administered monthly, unless ferritin concentration was greater than 700 µg/L or transferrin saturation was 40% or higher. The other group received a low-dose reactive iron strategy: IV iron sucrose in doses of 0 to 400 mg monthly, triggered by ferritin concentration less than 200 µg/L or transferrin saturation less than 20%.
The main outcome of interest was a composite of nonfatal myocardial infarction, nonfatal stroke, hospitalization for heart failure, or death, assessed as time to first event. The same outcomes were evaluated as recurrent events. Secondary outcomes included death, infections, and ESA dose.
At a median 2.1 years’ follow-up, median monthly iron dose was 264 mg with the proactive high-dose IV iron strategy compared to 145 mg with the reactive low-dose strategy. Median monthly ESA doses were 29,757 versus 38,805 IU, respectively, for a difference of -7539 IU.
A primary endpoint event occurred in 29.3% of patients in the high-dose group versus 32.3% in the low-dose group, with statistically significant hazard ratios for both noninferiority and superiority. The high-dose strategy was also superior on a composite secondary endpoint of fatal or nonfatal myocardial infarction: hazard ratio 0.69. There were 429 recurrent events in the high-dose group versus 507 in the low-dose group: rate ratio 0.77. Infection and hospitalization rates were similar between groups.
Intravenous iron is a standard part of care for maintenance hemodialysis patients. Large doses of iron are increasingly used to lower required doses of ESAs. With a lack of comparative studies, the use of high-dose iron varies widely.
In the PIVOTAL trial, a proactive, high-dose IV iron strategy is superior to a reactive, low-dose strategy. The high-dose strategy reduces the risk of death or major adverse cardiovascular events, as well as ESA dose. The results reflect a correction since the findings were presented at ASN Kidney Week 2018, with improvement in outcomes related to adjudicated myocardial infarction, nonfatal stroke, or hospitalization for heart failure [Macdougall IC, et al. Intravenous iron in patients undergoing maintenance hemodialysis. N Engl J Med 2019; 380:447–458].