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Revised data show higher iron levels reduce cardiovascular and mortality risk in patients with ESRD
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A re-analysis of data from the results of the Proactive IV Iron Therapy in Haemodialysis Patients trial, originally presented at a High Impact Clinical Trial Session during Kidney Week 2018, shows that higher iron stores in patients with ESRD not only help reduce the dosing levels for erythropoiesis-stimulating agents needed to treat anemia but also prove more effective in reducing cardiovascular-related hospitalizations and the risk of myocardial infarction compared with lower iron levels.
“[T]he effect of iron levels on cardiovascular events in hemodialysis patients has previously been given little recognition,” Javed Butler, MD, professor of cardiology at the University of Mississippi, said in a Vifor Pharma press release on the re-analysis. “The PIVOTAL trial has demonstrated the significant benefits of effective treatment with intravenous iron by improving major cardiovascular outcome parameters in this high-risk population.” Vifor manufactures Venofer, the IV iron drug used in the trial, and provided an unrestricted grant to Kidney Research UK to conduct the PIVOTAL trial.
The original results, published in the New England Journal of Medicine by McDougall and colleagues simultaneously with the Kidney Week 2018 session, concluded that the higher levels of iron stores reduced erythropoiesis-stimulating agent (ESA) doses and were not associated with higher risks of death, major adverse cardiovascular events or infection. However, the greater iron doses had no influence on cardiovascular or mortality risk.
The trial followed 2,141 patients (1,093 patients randomized to the high-dose group and 1,048 to the low-dose group) from 50 sites in the United Kingdom with a median follow-up of 2.1 years.
Patients in the high-dose group received a median monthly iron dose of 264 mg as compared with 145 mg in the low-dose group. For use of ESAs, the median monthly dose was 29,757 IU in the high-dose group and was 38,805 IU in the low-dose group. The study allowed ferritin levels of up to 700 µg/L and TSAT up to 40% in the high-dose group; the low-dose group allowed for serum ferritin of 200 µg/L and TSAT of 20%.
In the updated results, Vifor said the primary endpoint the composite of nonfatal myocardial infarction, nonfatal stroke, hospitalization for heart failure, or death – reached statistically significant superiority for the proactive, high-dose Venofer regimen compared with the low-dose Venofer group.
“Similarly, the rates of the individual components of fatal or non-fatal myocardial infarction and hospitalization for heart failure were lower among patients receiving high-dose IV iron. Results on deaths, as well as all safety endpoints (vascular access thrombosis, hospitalization for any cause and for infection), reduction in ESA dose requirements and number of blood transfusions did not differ between the two treatment arms,” Vifor said in the press release. The re-analysis was necessitated after “identification of a programming error in the original analysis by the investigators,” the company said.
Francesco Locatelli, MD , professor of nephrology at Hospital Alessandro Manzoni in Lecco, Italy, said in the release that the PIVOTAL trial “was a long-awaited landmark study in nephrology and the results mark a significant milestone in the treatment of hemodialysis patients. It is expected that the results from this study will impact guidelines and clinical practice for the benefit of these patients.” – by Mark E. Neumann
References:
MacDougall IC, et al. N Engl J Med. 2018;doi:10.1056/NEJMoa1810742.