Proactive IV Iron Therapy in Hemodialysis Patients - PIVOTAL

Jun 29, 2021
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Author/Summarized by Author:
Dharam J. Kumbhani, MD, SM, FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, MBA, FACC
Trial Sponsor:
Kidney Research UK (supported by an unrestricted grant from Vifor Fresenius Medical Care Renal Pharma).
Date Published:
06/28/2021
Date Updated:
06/29/2021
Original Posted Date:
06/29/2021
References

Contribution To Literature:

The PIVOTAL trial showed that high-dose iron therapy was superior to low-dose iron therapy (used in a reactive fashion) in reducing HF events among patients with ESRD on hemodialysis.

Description:

The goal of the trial was to assess the safety and efficacy of high-dose vs. low-dose iron infusion on heart failure (HF) events among end-stage renal disease (ESRD) patients.

Study Design

Patients were randomized in an open-label 1:1 fashion to either a regimen of high-dose intravenous (IV) iron administered proactively (n = 1,093) or a regimen of low-dose IV iron administered reactively (n = 1,048). In the high-dose group, 400 mg of iron sucrose was prescribed, with safety cutoff limits (ferritin >700 mg/L or a transferrin saturation [TSAT] >40%) above which further iron was withheld until the next test 1 month later. Patients in the low-dose group were prescribed 0-400 mg of iron sucrose monthly, as needed, to maintain ferritin ≥200 mcg/L and TSAT ≥20%.

  • Total number of enrollees: 2,141
  • Duration of follow-up: 2.1 years (median)
  • Mean patient age: 64 years
  • Percentage female: 35%

Inclusion criteria:

  • End-stage kidney disease in whom maintenance hemodialysis had been initiated no more than 12 months previously
  • Ferritin concentration <400 m g/L and TSAT <30%
  • Receiving an erythropoiesis stimulating agent (ESA)

Other salient features/characteristics:

  • Hemoglobin: 10.6 g/dl
  • Ferritin: 216 mcg/L

Principal Findings:

The primary endpoint, first fatal or nonfatal HF event for high-dose vs. low-dose iron, was 4.7% vs. 6.7% (p = 0.023).

Secondary outcomes:

  • HF hospitalizations: 3.8% vs. 6.5% (p = 0.003)
  • All-cause mortality: 22.5% vs. 25.7% (p = 0.054)
  • Cardiovascular death or HF hospitalization: 11.6% vs. 13.4% (p = 0.092)
  • First and recurrent HF events: 2.85 vs. 4.75 events per 100 person-years (p = 0.0084)

Interpretation:

The results of this trial indicate that high-dose iron therapy was superior to low-dose iron therapy (used in a reactive fashion) in reducing HF events among patients with ESRD on hemodialysis. Significant reductions in total and recurrent HF events were noted. Similar benefits have been noted among patients with HF with reduced ejection fraction and iron deficiency anemia.

References:

Jhund PS, Petrie MC, Robertson M, et al., on behalf of the PIVOTAL Investigators and Committees. Heart Failure Hospitalization in Adults Receiving Hemodialysis and the Effect of Intravenous Iron Therapy. JACC Heart Fail 2021;9:518-27.

Clinical Topics: Dyslipidemia, Heart Failure and Cardiomyopathies, Prevention, Lipid Metabolism, Acute Heart Failure

Keywords: Anemia, Iron-Deficiency, Dialysis, Ferritins, Heart Failure, Hemoglobins, Iron, Kidney Failure, Chronic, Renal Dialysis, Secondary Prevention, Stroke Volume, Transferrins, Vascular Diseases


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