Meta-analysis: Does FCM improve clinical outcomes in HF?

A large, pooled analysis using individual participant data to investigate the effects of ferric carboxymaltose (FCM) on clinical outcomes in patients with heart failure (HF) and iron deficiency displayed a significant reduction of the composite of cardiovascular (CV) hospitalisation and CV death at 1 year of follow up. This effect was mostly driven by a reduction in hospitalisations.

“Iron deficiency occurs in 50–80% of the patients with HF,” said Prof. Piotr Ponikowski (Medical University Wroclaw, Poland) [1]. “Although the positive effect of intravenous FCM on exercise capacity and quality-of-life has been demonstrated, its effect on clinical outcomes is less clear.” Prof. Ponikowski and colleagues conducted a pooled analysis of patient-level data including randomised, double-blind, placebo-controlled trials that investigated the effect of FCM on prospectively recorded HF hospitalisations, CV death, and all-cause death for a minimum duration of 52 weeks, in patients with HF and iron deficiency.

The CONFIRM-HF (NCT01453608), AFFIRM-AHF (NCT02937454), and HEART-FID (NCT03037931; also presented at ESC 2023) trials met the inclusion criteria [2–4]. “The meta-analysis included approximately 4,500 patients, with a mean age of 70 years, and about 40% of the patients were women,” added Dr Ponikowski. The co-primary endpoints were a composite of total CV hospitalisations and CV death through 52 weeks, and a composite of total HF hospitalisations and CV death through 52 weeks.

The endpoint of total CV hospitalisations and CV death was met, favouring FCM over placebo (rate ratio [RR] 0.86; 95% CI 0.75–0.98; P=0.029; see Figure). The endpoint of total HF hospitalisations and CV death just missed statistical significance but showed a trend towards a benefit for patients who were randomised to FCM compared with those on placebo (RR 0.87; 95% CI 0.75–1.01; P=0.076). Prof. Ponikowski added that these effects were driven by a reduction in CV hospitalisations (RR 0.83; 95% CI 0.73–0.96; P=0.009) and HF hospitalisations (RR 0.84; 95% CI 0.71–0.98; P=0.025) but not by a reduction in time to CV death (RR 0.97; 95% CI 0.80–1.17; P=0.72) or all-cause death (RR 0.93; 95% CI 0.78–1.10; P=0.39).

Furthermore, the subgroup analysis revealed one significant interaction effect: patients with transferrin saturation levels <15% benefitted significantly more from treatment with FCM in terms of CV hospitalisations and CV death than patients with transferrin saturation levels ≥24% (P_interaction=0.019). Finally, an exploratory analysis suggested that patients with a higher cumulative dose at 6 months may benefit more from treatment with FCM than those with lower cumulative doses.

Figure: Co-primary endpoint of total CV hospitalisations and CV death [1]



CI, confidence interval; CV, cardiovascular; FCM, ferric carboxymaltose; PBO, placebo.

“Based on the results of our meta-analysis, FCM should be considered as an option to reduce the risk for CV or HF hospitalisations in patients with HF with reduced or mildly reduced left ventricular ejection fraction and iron deficiency,” concluded Prof. Ponikowski. “Further research is needed to select the appropriate patients for this therapy and to assess the potential benefits of re-dosing in the first 6 months of treatment.”

1. 
   
   1. Ponikowski P, et al. Impact of ferric carboxymaltose (FCM) on heart failure-related clinical outcomes in patients with heart failure and iron deficiency: an individual participant data meta-analysis. Hot Line Session 2, ESC Congress 2023, 25–28 August, Amsterdam, the Netherlands.
   2. Ponikowski P, et al. Lancet. 2020;396(10266):1895–1904.
   3. Ponikowski P, et al. Eur Heart J. 2015;36(11):657–668.
   4. Mentz RJ, et al. The HEART-FID trial: efficacy and safety of ferric carboxymaltose as treatment for heart failure with iron deficiency. Hot Line Session 2, ESC Congress 2023, 25–28 August, Amsterdam, the Netherlands.

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Posted on 30 October, 202330 October, 2023