Intravenous ferric carboxymaltose for iron deficiency in heart failure patients: A meta-analysis with trial sequential analysis

BACKGROUND: Iron deficiency is present in roughly one-third to one-half of patients with chronic heart failure and is associated with worse outcomes. In this study, we aim to assess the impact of intravenous (IV) ferric carboxymaltose (FCM) administration on heart failure outcomes.

METHODS: We performed a comprehensive literature search of PubMed, Scopus, Cochrane Library, and Web of Science for randomized controlled trials (RCTs) up to May 2025. The outcomes of interest, including first heart failure hospitalization or cardiovascular death (primary outcome), total heart failure hospitalizations, and total all-cause hospitalization, were estimated using a fixed-effect model and reported as pooled risk ratios (RRs). Trial sequential analysis (TSA) was conducted to assess the robustness of the findings and estimate the required information size.

RESULTS: Nine RCTs were included, comprising 7491 patients. Compared to placebo, FCM significantly reduced the risk of hospitalization due to heart failure or cardiovascular death (RR 0.89, 95 % CI 0.83-0.96; P = 0.0016). Additionally, FCM lowered the risk of heart failure hospitalizations (RR 0.82, 95 % CI 0.77-0.87; P < 0.0001) and decreased the risk of cardiovascular death (RR 0.89, 95 % CI 0.80-0.99; P = 0.0384). However, there was no significant difference in total all-cause hospitalization between the groups (RR 0.93, 95 % CI 0.85-1.01; P = 0.0830). TSA demonstrated conclusive evidence for the primary outcome.

CONCLUSION: FCM reduces the risk of heart failure hospitalizations, cardiovascular hospitalizations, and cardiovascular death in iron-deficient heart failure patients, although it does not impact all-cause hospitalization, thereby supporting its utility as a targeted therapeutic strategy.

PROSPERO ID: CRD420251062092.