Ferric Carboxymaltose In Iron Deficient Patients Admitted For Acute Heart Failure (AFFIRM-AHF)

Presented during the AHA Scientific Sessions 2020 by Piotr Ponikowski (Wroclaw Medical University, Wroclaw, Poland).

Introduction and methods

In patients with heart failure (HF), iron deficiency is common. Iron deficiency in HF patients is associated with reduced exercise capacity, poor quality of life, increased risk of hospitalization and death. In patient with acute HF, iron deficiency is observed in up to 70% of patients and a predictor of poor outcomes, independent of history of HF, natriuretic peptides and ejection fraction.

The AFFIRM-AHF trial examined the effect of intravenous ferric carboxymaltose given shorty before discharge compared to placebo on recurrent HF hospitalizations and CV death after 52 weeks in patients with acute HF and iron deficiency.

Due to the outbreak of COVID-19, management and follow-up of patients was affected. Therefore, a COVID-19 sensitivity analysis was performed, censoring patients at the date of the country’s first reported COVID-19 patient.

1132 Patients hospitalized for acute HF with iron deficiency, LVEF <50% and hemoglobin 8-15 g/dL were included. After clinical stabilization, they were randomized in a 1:1 ratio to IV ferric carboxymaltose (given dose was based on the iron need) or to placebo, administered at randomisation and week 6. If iron deficiency persisted, study drug was administered to week 12 and week 24 (80% of patients required only 1 or 2 additional injections during the study period). Primary outcome was a composite of total HF hospitalizations and CV death at week 52. Secondary outcomes included total HF hospitalizations, CV death, time to first HF hospitalizations or CV death.

Main results

• There were 293 primary endpoint events in the IV ferric carboxymaltose group and 372 events in the placebo group (RR 0.79, 95%CI: 0.62-1.01, P=0.059).
• The individual outcome total HF hospitalizations was reduced in the IV ferric carboxymaltose group compared to the placebo group (217 events vs. 294 events, RR 0.74, 95%CI: 0.58-0.94, P=0.013).
• The secondary endpoint of first HF hospitalization or CV death was reduced in the IV ferric carboxymaltose group compared to the placebo group (181 events vs. 209 evens, RR 0.80, 95%CI: 0.66-0.98, P=0.030).
• The COVID-19 sensitivity analysis showed similar results, with a significant reduction for the primary endpoint of total HF hospitalization and CV death and the individual endpoint of total HF hospitalization with IV ferric carboxymaltose compared to placebo (RR 0.75, 95%CI: 0.59-0.96, P=0.024, and RR 0.70, 95%CI: 0.55-0.90, P=0.005, respectively).
• No reduction in CV death was observed, neither in the ITT population nor in the COVID-19 sensitivity analysis.
• Treatment with IV ferric carboxymaltose was safe and well tolerated.

Conclusion

In patients with acute HF and iron deficiency, administration of IV ferric carboxymaltose before discharge reduced the risk of HF hospitalization, but not CV death, when compared to placebo. In addition, the composite endpoint of first HF hospitalization or CV death was reduced by IV ferric carboxymaltose compared to placebo.

Discussion

Discussant Nancy Sweitzer, MD, PhD (Tucson, AZ,USA) started her presentation by discussing the poor outcomes in HF patients with chronic iron deficiency. Iron deficiency impairs cellular energetics and immunity, independent of anemia. She said that previous studies with IV iron replacement had been performed and demonstrated improvements in exercise capacity and quality of life, but data on harder outcomes were lacking. Therefore, the AFFIRM-HF trial was undertaken and demonstrated benefit on HF hospitalization with IV ferric carboxymaltose. She did raise some further questions of the mechanism of reduction in hospitalization, relationship of benefit to hemoglobin levels, outcomes of subgroupanalyses and challenges of implementation. In the end, she congratulated the investigators for conduct of such an important trial, that will likely change the guidelines.

- Our reporting is based on the information provided during AHA Scientific Sessions 2020 -

The findings of this study were simultaneously published in The Lancet