Intravenous ferric carboxymaltose in patients with heart failure and iron deficiency: a systematic review and meta-analysis of randomized controlled trials with trial sequential analysis

INTRODUCTION: Iron deficiency (ID) is common among patients with heart failure (HF), and it is associated with poor functional outcomes, increased hospitalizations, and higher mortality. This meta-analysis evaluates the efficacy of intravenous ferric carboxymaltose (FCM) in HF patients with ID. METHODS: We conducted a literature search of major bibliographic databases up to 15 April 2025, to identify randomized controlled trials (RCTs) comparing FCM with placebo or standard care in HF patients with ID. The primary outcome was a composite of recurrent hospitalizations for heart failure (HHF) or cardiovascular (CV) death assessed at 1-year and complete follow-up. Risk ratios (RR) and mean differences (MD) with 95% confidence intervals (CI) were estimated using a random-effects model. RESULTS: Eleven RCTs enrolling 6493 patients (3329 FCM; 3164 control) were included. The mean age of patients was 66.7 ± 10.6 years, 34.4% were women, mean left ventricular ejection fraction was 33.7 ± 8.8%, mean haemoglobin was 12.4 ± 1.8 g/dL, and mean transferrin saturation was 18.9 ± 10.1%. FCM significantly reduced the composite of recurrent HHF or CV death at 1-year (RR 0.73, 95% CI 0.62-0.85) and over maximum follow-up (RR 0.80, 95% CI 0.68-0.94) compared to control. Recurrent HHF was significantly reduced with FCM administration (1-year RR 0.69, 95% CI 0.57-0.84; complete follow-up RR 0.75, 95% CI 0.60-0.94). FCM demonstrated a trend towards reduced all-cause (RR: 0.86, 95% CI: 0.74-1.00) and CV mortality at 1-year (RR: 0.86, 95% CI: 0.72-1.02), but this effect was attenuated over longer follow-up. FCM significantly improved 6-minute walk test performance (MD 29.19 m, 95% CI 11.95-46.43). The trial sequential analysis confirmed robust evidence for the primary outcome. CONCLUSION: Intravenous FCM in HF patients is associated with reduced risk of adverse cardiovascular events and improved functional capacity. Further trials are needed to clarify its long-term survival impact.