Lower risk of HF hospitalizations with ferric carboxymaltose in patients with iron deficiency, stabilized after acute HF
Ferric carboxymaltose for iron deficiency at discharge after acute heart failure: a multicentre, double-blind, randomised, controlled trial
Introduction and methods
Iron deficiency in patients with acute heart failure is common and associated with poor prognosis [1-5], regardless of anemia. Two randomized clinical trials (FAIR-HF and CONFIRM-HF) have shown that intravenous (IV) ferric carboxymaltose (FCM) improved symptoms, exercise tolerance, and quality of life in iron deficient patients with HFrEF [6,7]. And a meta-analysis reported that FCM therapy was associated with decreased total HF hospitalizations and CV deaths in these patients. However, the effect of FCM treatment on outcomes of CV death or HF hospitalization in patients with iron deficiency who were admitted to hospital for acute HF has not prospectively been investigated.
This study assessed the effect of IV FCM or placebo on morbidity and mortality in patients with iron deficiency after hospitalization for acute HF.
The AFFIRM-AHF was a multicenter, randomized, double-blind, placebo-controlled trial that included patients hospitalized with acute HF, LVEF <50% and iron deficiency between March 21, 2017 and July 30, 2019. Iron deficiency was defined as serum ferritin < 100 ng/mL or 100-299 ng/mL with transferrin saturation levels <20%. Patients (n=1132) were randomized (1:1) to receive FCM or placebo shortly before discharge from the hospital. The second dose was administrated at week 6. Subsequent doses of study treatment were given to patients with persistent iron deficiency at weeks 12 and 24. Efficacy and safety outcomes were assessed at week 4, 12, 36, and 52. Primary outcome was a composite of total HF hospitalizations and CV death up to 52 weeks after randomization. Secondary outcomes included the composite of total CV hospitalization and CV death, total HF hospitalizations, CV death, total CV hospitalization, time to first HF hospitalization or CV death, and days lost because of HF hospitalization or CV death. Follow-up was 52 weeks.
- The primary event was 293 times observed in 558 patients treated with FCM compared to 372 events in 550 patients receiving placebo (RR 0.79, 95% CI: 0.62-1.01, P=0.059). The effect of FCM was consistent across prespecified subgroups and independent from age, anemia, and NT-proBNP levels.
- 370 CV hospitalizations and CV deaths occurred in the FCM group compared to 451 events in the placebo group (RR 0.80, 95% CI: 0.64-1.00, P=0.050).
- Patients on FCM were less frequently hospitalized for HF compared to those on placebo (217 vs. 294 hospitalizations, respectively, RR 0.74, 95% CI: 0.58-0.94, P=0.013).
- The incidence of CV death was similar in both groups (HR 0.96, 95% CI: 0.70-1.32).
- 32% Of patients treated with FCM had a first HF hospitalization or CV death compared to 38% of patients on placebo (HR 0.80, 95% CI: 0.66-0.98, P=0.030).
- Patients treated with FCM lost 369 days per 100 patient-years due to HF hospitalization and CV death compared to 548 days per 100 patient-years for patients receiving placebo (RR 0.67, 95% CI: 0.47-0.97, P=0.035).
- There were 295 CV hospitalizations in the FCM group compared to 374 in the placebo group (RR 0.77, 95% CI: 0.62-0.95, P=0.015).
- In the FCM group, 80% of patients received either 1 or 2 administrations of IV FCM throughout the treatment phase. The mean total dose of FCM during the trial was 1352 mg (SD 568 mg).
- FCM treatment was safe and well tolerated.
- There was a significant reduction in the primary composite endpoint for patients on FCM compared to placebo when applying a pre-COVID-19 sensitivity analysis (RR 0.75, 95% CI: 0.59-0.96, P=0.024). CV death was not reduced by FCM compared to placebo in this sensitivity analysis.
Patients with iron deficiency hospitalized for acute HF, who were treated with IV FCM were less frequently hospitalized for HF compared to those receiving placebo. FCM treatment had no effect on CV death.