High-dose IV iron decreases occurrence of first and recurrent HF events in patients on hemodialysis

Introduction and methods

Patients with CKD are at high risk of developing HF [1,2]. To date, no treatment has been shown to reduce HF events in hemodialysis patients. The current analysis of the PIVOTAL trial assessed the effect of IV iron therapy either administered proactively in a high-dose regimen or administered reactively in a low-dose regimen on HF events in adults receiving hemodialysis.

The PIVOTAL trial [3,4] enrolled adults with end-stage kidney disease receiving maintenance hemodialysis for no more than 12 months. Included patients had ferritin <400 µg/L, TSAT <30% and were receiving erythropoiesis stimulating agents (ESAs). Existing iron therapy was stopped and ferritin concentration and TSAT were measured monthly. A total of 2141 patients were randomized (1:1) to receive either high-dose IV iron administered proactively (a monthly dose of 400 mg of iron sucrose. Safety cutoff limits were ferritin >700 µg/L or TSAT >40%) or low-dose IV iron administered reactively (0 to 400 mg of iron sucrose monthly, to maintain ferritin ≥200 µg/L and TSAT ≥20%). The primary composite outcome of the PIVOTAL trial was MI, stroke, HF hospitalization or all-cause death. HF hospitalization was an adjudicated outcome, component of the primary composite outcome and prespecified secondary outcome of the trial. The current analysis focused on the following outcomes: first HF hospitalization or HF death (i.e. first fatal or nonfatal HF event), first HF hospitalization or CV death, and total (first and recurrent) HF events. Median follow-up was 2.1 years.

Main results

• The composite outcome of first fatal or nonfatal HF event (HF death or HF hospitalization) occurred less often during follow-up in the high-dose iron group (51 of 1093 patients, 4.7%), compared to the low-dose iron group (70 of 1048 patients, 6.7%; HR 0.66, 95%CI 0.46-0.94, P=0.023).
• HF hospitalization occurred in 3.8% of patients (42 of 1093) in the high-dose group and 6.5% of patients (68 of 1048) in the low-dose group (HR 0.56, 95%CI 0.38-0.82, P=0.003). The composite outcome of CV death or HF hospitalization occurred in 11.6% of patients (126 of 1093) in the high-dose group and in 13.4% of patients in the low-dose group (140 of 1048; HR 0.81, 95%CI 0.64-1.03, P=0.092). There was no significant difference between groups for the outcomes of HF death, CV death or all-cause death.
• A total of 63 first and recurrent events occurred in the high-dose group (2.83 events per 100 person-years), compared to 98 in the low-dose group (4.75 events per 100 person-years; rate ratio 0.59, 95%CI 0.40-0.87, P=0.0084).
• Independent predictors of first HF hospitalization or HF death were history of diabetes and history of HF at baseline.

Conclusion

References

Find this article online at JACC Heart Fail.