ArticlesFerric carboxymaltose for iron deficiency at discharge after acute heart failure: a multicentre, double-blind, randomised, controlled trial
Introduction
Iron deficiency is common in patients with heart failure1, 2, 3 and is associated with exercise intolerance, poor quality of life,4, 5 and increased risk for hospitalisation and mortality,2, 3 regardless of the presence or absence of anaemia. Randomised clinical trials have shown that intravenous ferric carboxymaltose improves symptoms, exercise capacity, and quality of life in ambulatory patients with chronic heart failure and left ventricular ejection fraction of 45% or less who have iron deficiency.6, 7 An individual patient data meta-analysis reported that treatment with ferric carboxymaltose was associated with a lower rate of total heart failure hospitalisations or cardiovascular mortality in these patients.8 However, it has never been prospectively investigated whether this therapy could favourably affect outcomes in iron-deficient patients after admission for acute heart failure, when risk of rehospitalisation and mortality is high.
Hospitalisations due to acute heart failure represent a growing health-care problem associated with a high risk of adverse clinical outcomes and a large economic burden.9 Iron deficiency is common in patients with acute heart failure and is associated with poor prognosis.10, 11 Patients with an episode of acute heart failure and concomitant iron deficiency constitute a high-risk target population, in whom treatment of iron deficiency with intravenous iron could translate into a positive effect on outcomes.
AFFIRM-AHF (A Randomised, Double-blind Placebo Controlled Trial Comparing the Effect of Intravenous Ferric Carboxymaltose on Hospitalisations and Mortality in Iron Deficient Subjects Admitted for Acute Heart Failure) was designed to evaluate the effect of intravenous ferric carboxymaltose or placebo initiated shortly before hospital discharge in patients with acute heart failure and iron deficiency on total heart failure hospitalisations and cardiovascular death up to 52 weeks after randomisation.
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Study design
AFFIRM-AHF was a multicentre, randomised, double-blind, placebo-controlled trial done at 121 sites in Europe, South America, and Singapore (appendix pp 3–8). The study design has been published previously.12 The trial protocol and subsequent amendments and the statistical analysis plan are provided in the appendix (pp 181–607). The protocol and amendments were approved by the institutional review boards at each participating centre. The trial was conducted in accordance with the Declaration of
Results
Between March 21, 2017, and July 30, 2019, 1525 patients at 121 sites in 15 countries were screened. 1132 patients were randomly assigned to receive either ferric carboxymaltose (n=567) or placebo (n=565). Study treatment was started in 1110 patients and at least one post-randomisation value was available for 1108 patients (figure 1). Patient characteristics and medications at baseline were balanced between treatment groups (table 1). At trial closure (July 24, 2020), fatal and non-fatal
Discussion
The findings of AFFIRM-AHF show that, compared with placebo, treatment with ferric carboxymaltose, initiated at hospital discharge in stabilised patients with acute heart failure and concomitant iron deficiency, resulted in an RR for the combined endpoint of total heart failure hospitalisations and cardiovascular death of 0·79 (95% CI 0·62–1·01, p=0·059) which falls just short of conventional 5% statistical significance. The total number of heart failure hospitalisations was significantly lower
Data sharing
Data underlying the findings described in this manuscript may be obtained in accordance with Vifor Pharma's data sharing policy. Enquiries can be made to [email protected].
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