High-dose IV iron decreases occurrence of first and recurrent HF events in patients on hemodialysis
Heart Failure Hospitalization in Adults Receiving Hemodialysis and the Effect of Intravenous Iron Therapy
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.
- 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.
Treatment with high-dose IV iron administered proactively, compared to low-dose IV iron administered reactively, decreased the occurrence of first and recurrent HF events in adults receiving hemodialysis.