Intravenous Iron Dosing and Infection Risk in Patients on Hemodialysis: A Prespecified Secondary Analysis of the PIVOTAL Trial

Significance StatementExperimental and observational data have raised concerns that intravenous (IV) iron might increase the risk of infections. In this analysis from the Proactive IV Iron Therapy in Haemodialysis Patients (PIVOTAL) trial involving 2141 patients on hemodialysis randomly assigned to receive either a high-dose or low-dose IV iron regimen, investigators reported finding no evidence that the two groups differed in incidence of infection, hospitalization for infection, or death from infection. Given the potential cardiovascular benefits of higher-dose IV iron seen in the PIVOTAL trial (due to either a direct effect of the IV iron or a decreased use of erythropoiesis-stimulating agents and thus, less exposure to associated cardiotoxic effects), this analysis provides reassurance for administering higher doses of IV iron than are currently given in many units worldwide. BackgroundExperimental and observational studies have raised concerns that giving intravenous (IV) iron to patients, such as individuals receiving maintenance hemodialysis, might increase the risk of infections. The Proactive IV Iron Therapy in Haemodialysis Patients (PIVOTAL) trial randomized 2141 patients undergoing maintenance hemodialysis for ESKD to a high-dose or a low-dose IV iron regimen, with a primary composite outcome of all-cause death, heart attack, stroke, or hospitalization for heart failure. Comparison of infection rates between the two groups was a prespecified secondary analysis.MethodsSecondary end points included any infection, hospitalization for infection, and death from infection; we calculated cumulative event rates for these end points. We also interrogated the interaction between iron dose and vascular access (fistula versus catheter).ResultsWe found no significant difference between the high-dose IV iron group compared with the lose-dose group in event rates for all infections (46.5% versus 45.5%, respectively, which represented incidences of 63.3 versus 69.4 per 100 patient years, respectively); rates of hospitalization for infection (29.6% versus 29.3%, respectively) also did not differ. We did find a significant association between risk of a first cardiovascular event and any infection in the previous 30 days. Compared with patients undergoing dialysis with an arteriovenous fistula, those doing so via a catheter had a higher incidence of having any infection, hospitalization for infection, or fatal infection, but IV iron dosing had no effect on these outcomes.ConclusionsThe high-dose and low-dose IV iron groups exhibited identical infection rates. Risk of a first cardiovascular event strongly associated with a recent infection.