Introduction: Despite the evidence indicating beneficial effects of the treatment of iron deficiency in heart failure (HF) patients using intravenous iron supplementation, there is a lack of studies addressing the effectiveness of oral iron therapy in this population.
Purpose: Investigate the efficacy of oral iron administration in patients with stable chronic HF and iron deficiency, and correlate this response with the degree of inflammatory activity and the baseline assessment of oral iron absorption.
Methods: We conducted a placebo-controlled, double-blind and randomized clinical trial that included patients with symptomatic stable chronic HF (NYHA II-III), LVEF<45%, and iron deficiency with ferritin<100ng/mL or ferritin between 100–300ng/mL with transferrin saturation (Tsat)<20%, independently of the presence of anemia (hemoglobin values between 9–16g/dL). Total of 30 patients were allocated, in 2:1 ratio, to treatment with 180mg of ferrous sulfate (n=20) or administration of placebo (n=10), 3x/day. Primary end-point investigated was the level of Tsat after 4-months of follow-up. Secondary end-points were changes in hematimetrics indexes, LVEF in Echocardiogram, functional capacity assessed by cardiopulmonary exercise test (peak-VO2), NT-pro-BNP levels, and auto-perception of quality of life (QoL) using the Minnesota Living Heart Failure Questionare. Oral iron absorption test, and inflammatory cytokines IL-1β, IL-6 and TNF-α were performed only in the baseline.
Results: Of 30 patients initially included, 18 ended the study protocol: 7 patients in the control group (CG, 58.3±8.2 y.o., 42.9% males, LVEF=26.6±5.7%) and 11 in the intervention group (IG, 67.5±12.0 y.o., 63.6% males, LVEF=31.2±6.4%). The IG showed no significant increase in Tsat after intervention (24.4±8.5%) as compared to the baseline (22.8±9.2%), p=0.55. The Tsat in the CG was comparable to the IG in the baseline (16.1±8.2% and 22.8±9.2%, respectively, p=0.14) and after intervention (20.5±7.7% and 24.4±8.5%, respectively, p=0.33). The post-intervention results in the IG, as compared to the baseline, showed respectively: no significant change in peak-VO2 (12.1±2.9 to 10.2±3.1ml/kg/min, p=0.11), NT-pro-BNP levels (2855.0±1375.6 to 2750.7±1577.0pg/mL, p=0.77), LVEF (31.1±7.0 to 31.7±6.8%, p=0.70), and QoL score (8.3±10.0 to 8.1±5.9 points, p=0.98), but increased values of ferritin (102.5±56.2 to 67.8±29.0ng/mL, p=0.04). Iron absorption test at baseline showed significant increase of serum iron from the pre-dose (88.7±25.0μg/dL) to 180-min after oral dose (159.5±71.3μg/dL), p<0.01. The baseline IL-6 levels had negative correlation with ferritin variation and IL-1β with serum iron change. There was no difference in side effects rate in IG (25.0%) as compared to the CG (42.9%), p=1.00.
Conclusion: The results of this pilot study suggest that oral iron administration in stable systolic chronic HF patients with iron deficiency had neutral effect in Tsat, LVEF, functional capacity and QoL.