Intravenous iron supplement for iron deficiency in patients with severe aortic stenosis scheduled for transcatheter aortic valve implantation: results of the IIISAS randomised trial

Abstract

Aims: The aim of this trial was to evaluate whether intravenous iron could provide benefit beyond transcatheter aortic valve implantation (TAVI) in iron-deficient patients with severe aortic stenosis.

Methods and results: In this randomised, placebo-controlled, double-blind, single-centre trial, we enrolled patients with severe aortic stenosis and iron deficiency (defined as ferritin <100 µg/L, or 100-299 µg/L with a transferrin saturation <20%) who were evaluated for TAVI. Patients were randomly assigned (1:1) to receive intravenous ferric derisomaltose or placebo ∼3 months before TAVI. The primary endpoint was the between-group, baseline-adjusted 6-min walk distance measured 3 months after TAVI. Secondary outcomes included quality of life, iron stores, hand grip strength, New York Heart Association (NYHA) class, and safety. Between January 2020 and September 2021, we randomised 74 patients to ferric derisomaltose and 75 patients to placebo. The modified intention-to-treat population comprised the 104 patients who completed the 6-min walk test at baseline and 3 months after successful TAVI. Iron stores were restored in 76% of the patients allocated to iron and 13% of the patients allocated to placebo (p < 0.001). There was no difference in the baseline-adjusted 6-min walk distance between the two treatment arms (p = 0.82). The number of serious adverse events, quality of life, hand grip strength, and NYHA class did not differ between the treatment arms.

Conclusion: Treatment with intravenous iron did not provide clinical benefit beyond TAVI in iron-deficient patients with severe aortic stenosis.

Clinical trial registration: ClinicalTrials.gov NCT04206228.

Keywords: Aortic stenosis; Iron deficiency; Randomized controlled trials; Safety.

© 2022 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.

Figures

Figure 1

Flowchart of the IIISAS study population. AVR, aortic valve replacement; TAVI, transcatheter aortic valve implantation.

Figure 2

Changes in ferritin and 6‐min walk distance. The left panel illustrates the change in ferritin (µg/L) stratified by treatment allocation. The right panel illustrates the change in the 6‐min walk distance (m) stratified by treatment allocation. P‐value for the between‐treatment group difference in the baseline adjusted values of ferritin and walk distance. Boxes: 25–75 percentiles; whiskers: 10–90 percentiles.

Figure 3

Subgroup analyses. The plot shows the impact of intravenous iron on the 6‐min walk distance in five prespecified subgroups. The boxes represent the between‐group difference in the 6‐min walk distance and the lines indicate the lower and upper boundaries for the confidence intervals. Box sizes are proportional to the number of patients in each subgroup. 6MWT, 6‐min walk test; TSAT, transferrin saturation.