Physicians' Academy for Cardiovascular Education

Effects of ferric carboxymaltose for iron deficiency in acute HF by hemoglobin level

Association Between Hemoglobin Levels and Efficacy of Intravenous Ferric Carboxymaltose in Patients With Acute Heart Failure and Iron Deficiency: An AFFIRM-AHF Subgroup Analysis

Literature - Filippatos G, Ponikowski P, Farmakis D, et al. - Circulation. 2023 Apr 13 [Online ahead of print]. doi: 10.1161/CIRCULATIONAHA.122.060757

Introduction and methods


In HF patients, both iron deficiency and anemia are associated with an increased risk of hospitalization and mortality [1-7]. Interestingly, in patients with chronic HF, baseline hemoglobin levels do not influence the prognostic role of iron deficiency and the beneficial effects of treatment with ferric carboxymaltose (FCM) [1,4,8,9]. The role of iron deficiency and its treatment in relation to hemoglobin levels remains to be elucidated in patients with recent acute HF (AHF), a population with higher morbidity and mortality than a chronic HF population.

The AFFIRM-AHF trial recently showed intravenous FCM treatment reduced the risk of HF hospitalization and improved quality of life (QoL) compared with placebo in patients with iron deficiency who had been stabilized after an AHF episode [10]. However, FCM had no significant effect on the composite primary endpoint of HF hospitalization and CV death.

Aim of the study

In a prespecified exploratory subgroup analysis of the AFFIRM-AHF trial, the authors investigated the effects of intravenous FCM compared with placebo on clinical and QoL outcomes in iron-deficient patients with baseline hemoglobin values <12 g/dL versus ≥12 g/dL after stabilization following an AHF episode.


The AFFIRM-AHF trial was an international, multicenter, double-blind, placebo-controlled, phase 4 RCT in which 1108 patients hospitalized with signs and symptoms typical of AHF who had LVEF<50% and concomitant iron deficiency were randomized to intravenous FCM or placebo administered shortly before hospital discharge and for up to 24 weeks thereafter. Iron deficiency was defined as serum ferritin <100 μg/L, or serum ferritin 100–299 μg/L with transferrin saturation (TSAT) <20%. Patients with hemoglobin >15 g/dL were excluded.

In this subgroup analysis, 1107 patients with a baseline hemoglobin measurement were included: 464 patients in the subgroup with low hemoglobin levels (i.e., <12 g/dL; 228 treated with FCM and 236 with placebo) and 643 in the subgroup with normal hemoglobin levels (i.e., ≥12 g/dL; 329 treated with FCM and 314 with placebo).


The primary endpoint was a composite outcome of total HF hospitalizations and CV death up to 52 weeks. Secondary endpoints included a composite outcome of total CV hospitalizations and CV death; time to CV death; total HF hospitalizations; time to first HF hospitalization or CV death; and days lost due to HF hospitalization or CV death.

Additional outcomes were, among others, changes in disease-specific QoL assessed using the self-administered 12-item Kansas City Cardiomyopathy Questionnaire (KCCQ-12), hemoglobin, serum ferritin, and TSAT levels, and adverse events.

Main results

Primary and secondary endpoints

Additional outcomes


In this prespecified exploratory subgroup analysis of the AFFIRM-AHF trial in patients with iron deficiency who had been stabilized after an AHF episode, no significant interaction between hemoglobin subgroup (<12 vs. ≥12 g/dL) and the effect of treatment with intravenous FCM versus placebo was observed for the composite primary endpoint of HF hospitalization and CV death or any of the related secondary endpoints . FCM improved several iron parameters over time in both hemoglobin subgroups and also improved QoL in the second month in the group with normal hemoglobin levels .


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Find this article online at Circulation.

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