Ferric carboxymaltose and exercise capacity in heart failure with preserved ejection fraction and iron deficiency: the FAIR-HFpEF trial

Abstract

Background and aims: Evidence is lacking that correcting iron deficiency (ID) has clinically important benefits for patients with heart failure with preserved ejection fraction (HFpEF).

Methods: FAIR-HFpEF was a multicentre, randomized, double-blind trial designed to compare intravenous ferric carboxymaltose (FCM) with placebo (saline) in 200 patients with symptomatic HFpEF and ID (serum ferritin < 100 ng/mL or ferritin 100-299 ng/mL with transferrin saturation < 20%). The primary endpoint was change in 6-min walking test distance (6MWTD) from baseline to week 24. Secondary endpoints included changes in New York Heart Association class, patient global assessment, and health-related quality of life (QoL).

Results: The trial was stopped because of slow recruitment after 39 patients had been included (median age 80 years, 62% women). The change in 6MWTD from baseline to week 24 was greater for those assigned to FCM compared to placebo [least square mean difference 49 m, 95% confidence interval (CI) 5-93; P = .029]. Changes in secondary endpoints were not significantly different between groups. The total number of adverse events (76 vs. 114) and serious adverse events (5 vs. 19; rate ratio 0.27, 95% CI 0.07-0.96; P = .043) was lower with FCM than placebo.

Conclusions: In patients with HFpEF and markers of ID, intravenous FCM improved 6MWTD and was associated with fewer serious adverse events. However, the trial lacked sufficient power to identify or refute effects on symptoms or QoL. The potential benefits of intravenous iron in HFpEF with ID should be investigated further in a larger cohort.

Keywords: Exercise capacity; Heart failure; Iron deficiency; Preserved ejection fraction.

Structured Graphical Abstract

Main design features and outcomes of the FAIR-HFpEF trial. AF, atrial fibrillation; BNP, B-type natriuretic peptide; HF, heart failure; LVEF, left ventricular ejection fraction; NT-proBNP, N-terminal pro-B-type natriuretic peptide; NYHA, New York Heart Association; TSAT, transferrin saturation.

Figure 1

Consort diagram for trial disposition

Figure 2

Detailed results on changes in 6-min walking test distance. (A) Results over time until week 52 for the whole population (arrows indicate dosing visits). (B) Individual data (baseline to week 24) for patients with haemoglobin (Hgb) < 12.0 g/dL or ≥ 12.0 g/dL

Figure 3

Results over time for (A) Kansas City Cardiomyopathy Questionnaire and (B) European Quality of Life-5 Dimensions-3L