Table 1.
Main trials of iron supplementation in heart failure.
| Trial | Pts (n) | Design | Study drug | Inclusion criteria | Primary endpoint | Results |
|---|---|---|---|---|---|---|
| IRON-5 HF | 54 | Double blind randomized controlled | Oral ferrous sulfate 200 mg t.i.d for 90 days | LVEF <50% NYHA II-III (able to perform 6MWT) | Change 6MWT | Terminated early |
| IRONOUT HF | 225 | Phase 2 double-blind placebo-controlled randomized | Oral iron polysaccharide 150 mg twice daily for 16 weeks | LVEF ≤ 40% with NYHA II through IV symptoms | Change in peak VO2 from baseline to 16 weeks | High-dose of oral iron did not improve exercise capacity over 16 weeks |
| FERRIC HF | 35 | Randomized controlled observer-blinded | IV iron sucrose weekly for 16 weeks (Each dose was administered as 200-mg aliquots in 50 ml normal saline infused over 30 min) | CHF (NYHA II or III) with LVEF ≤ 45% | Change in absolute pVO2 | Intravenous iron loading improved exercise capacity and symptoms |
| FAIR HF | 459 | Double-blind placebo-controlled randomized | FCM (intravenous bolus injection of 4 ml) weekly until iron repletion was achieved, then every 4 weeks during the maintenance phase, which started at week 8 or week 12 | CHF (NYHA II or III), LVEF of 40% or less (for patients with NYHA II) or 45% or less (for NYHA III) | Self-reported Patient Global Assessment and NYHA functional class at week 24 | Intravenous ferric carboxymaltose improves symptoms, functional capacity, and quality of life |
| CONFIRM HF | 304 | Double-blind placebo-controlled randomized | FCM solution given as undiluted bolus i.v., injections of 500 or 1,000 mg of iron, administered over at least 1 min | Ambulatory symptomatic HF patients with LVEF ≤ 45% | Change 6 MWT distance from baseline to Week 24 | Sustainable improvement in functional capacity, symptoms, and QoL in patients treated with FCM |
| EFFECT HF | 172 | Prospective randomized controlled multicenter open-label trial with blinded end-point evaluation | FCM as an undiluted intravenous bolus injection or an infusion of 500 or 1,000 mg administered diluted in ≈100 mL of sodium chloride solution and given in ≥6 min for 10 mL | HFrEF (LVEF ≤ 45%) | Change in peak VO2 from baseline to 24 weeks measured by CPET | Favorable effect on peak VO2 was observed in patients treated with FCM. |
| AFFIRM-AHF | 1,132 | Double-blind placebo-controlled randomized | FCM administered as an undiluted bolus injection | Patients Admitted for Acute Heart Failure with LVEF <50% | The composite of recurrent HF hospitalizations and CV death up to 52 weeks | Pts actively treated had significantly fewer hospitalization for HF |
Pts, patients; FCM, ferric carboxymaltose; iv, intravenous; LVEF, left ventricular ejection fraction; HFrEF, heart failure with reduced ejection fraction; 6MWT, six minute walking test; CPET, cardiopulmonary exercise test.