FCM Reduces Recurrent HF and CV Hospitalizations in Patients With HF and Iron Deficiency

Intravenous ferric carboxymaltose (FCM) is associated with a significantly decreased risk for hospital admissions for heart failure (HF) and cardiovascular (CV) causes among iron-deficient patients with HF and reduced left ventricular ejection fraction (LVEF), according to a study in the European Heart Journal.

Researchers conducted a meta-analysis using individual participant data from 3 long-term, placebo-controlled, double-blind, randomized clinical trials (CONFIRM-HF, AFFIRM-AHF, and HEART-FID). The trials included adult patients with HF and iron deficiency, used FCM as an active treatment for iron deficiency, had 52 weeks or longer of follow-up, and prospectively reported outcomes including first and recurrent HF and CV hospitalizations, CV death, and all-cause death. A systematic review was performed in PubMed for trials published between July 19, 2013, and July 18, 2023, and the results of the IRONMAN trial were included in a sensitivity analysis.

The prespecified coprimary efficacy endpoints were a composite of recurrent CV hospitalizations and death for any CV reason and a composite of recurrent HF hospitalizations and CV death at 52 weeks.

The 3 trials randomly assigned 4501 patients to receive FCM (n=2251) or placebo (n=2250). The cohort had a mean age of 69.2 (SD 11.0) years, a mean LVEF of 31.6% (SD 8.1%), and 63% were men.

FCM therapy significantly decreased the coprimary composite endpoint of CV death and total CV hospitalizations vs placebo (rate ratio [RR], 0.86; 95% CI, 0.75-0.98; P =.029), without evidence of trial heterogeneity. A similar trend toward a decrease of the coprimary composite endpoint of CV death and total HF hospitalizations also was observed (RR, 0.87; 95% CI, 0.75-1.01; P =.076), without evidence of trial heterogeneity.

FCM therapy was associated with a 17% relative rate reduction in total CV hospitalizations (RR, 0.83; 95% CI, 0.73-0.96; P =.009) as well as a 16% relative rate reduction in total HF hospitalizations (RR, 0.84; 95% CI, 0.71-0.98; P =.025). FCM therapy did not affect the time to CV death (hazard ratio [HR], 0.97; 95% CI, 0.80-1.17; P =.72).

In subanalyses, evidence was observed for a significant interaction between transferrin saturation (TSAT) and the composite of CV hospitalization and CV death (P_interaction =.019) and for CV death (P_interaction =.035). Participants in the lowest TSAT tertile (<15%) had a greater treatment effect compared with those who had a higher baseline TSAT. A similar pattern occurred regarding the effect of TSAT on total HF hospitalizations and CV death (P_interaction =.095).

FCM therapy was associated with a decreased time to first CV death or HF hospitalization by 12% (HR, 0.88; 95% CI, 0.78-0.99; P =.039) as well as the time to first CV death or CV hospitalization by 11% (HR, 0.89; 95% CI, 0.80-0.99; P =.033).

The FCM and placebo groups had rates of serious treatment-emergent infections of 9.9 per 100 patient-years and 9.6 per 100 patient-years, respectively. No deaths were reported as resulting from serious treatment-related treatment-emergent adverse events.

Among several limitations, the researchers did not have access to the individual participant data from the IRONMAN trial, and the follow-up was limited to 12 months in the main analyses. “Importantly, our findings support continued research to identify those patients who are most likely to benefit from treatment with intravenous iron, particularly as it relates to the criteria used to identity ID [iron deficiency] and eligibility for initial and repeat iron doses,” the investigators wrote.