Effect of iron supplementation in patients with heart failure and iron deficiency: A systematic review and meta-analysis

Abstract

Background The effectiveness of oral and intravenous iron supplementation in reducing the risk of mortality and hospitalizations in HF patients with iron deficiency is not well-established. Methods A thorough literature search was conducted across 2 electronic databases (Medline and Cochrane Central) from inception through March 2021. RCTs assessing the impact of iron supplementation on clinical outcomes in iron deficient HF patients were considered for inclusion. Primary end-points included all-cause mortality and HF hospitalization. Evaluations were reported as odds ratios (ORs) or risk ratios (RRs) with 95% confidence intervals (CI) and analysis was performed using a random effects model. I 2 index was used to assess heterogeneity. Results From the 2599 articles retrieved from initial search, 10 potentially relevant studies (n = 2187 patients) were included in the final analysis. Both oral (OR: 0.93; 95% CI: 0.08–11.30; p = 0.951) and intravenous (OR: 0.97; 95% CI: 0.73–1.29; p = 0.840) iron supplementation did not significantly reduce all-cause mortality. However, intravenous iron supplementation significantly decreased the rates of overall (OR: 0.52; 95% CI: 0.33–0.81; p = 0.004) and HF (OR: 0.42; 95% CI: 0.22–0.80; p = 0.009) hospitalizations. In addition, intravenous ferric carboxymaltose therapy significantly reduced the time to first HF hospitalization or cardiovascular mortality (RR = 0.70; 95% CI = 0.50–1.00; p = 0.048), but had no effect on time to first cardiovascular death (RR: 0.94; 95% CI: 0.70–1.25; p = 0.655). Conclusion Oral or intravenous iron supplementation did not reduce mortality in iron deficient HF patients. However, intravenous iron supplementation was associated with a significant decrease in overall and HF hospitalizations.

Expression of Iron Metabolism Proteins in Patients with Chronic Heart Failure

“…In HF hearts, the highest number of significant correlations (p < 0.05) we found for: DMT-1 (11); L-CH (10); and TfR-1, FT-H, ACO-1. The highest number of moderate/strong correlations r ≥ 0.5, p < 0.05 we found for L-CH (4). The main correlations between iron transport, storage and regulatory proteins were positive, except hepcidin, which was negatively correlated with L-CH and FPN.…”

“…Several studies and clinical trials have demonstrated that iron supplementation in HF patients has improved their quality of life and functional capacity, significantly reducing the risk of first hospitalization and hospital readmissions, and improving peak oxygen consumption and functional capacity (measured by a 6-min test walk) [17]. However, some of cardiologists question the beneficial role of iron supplementation in the course of HF, pointing to the lack of significant improvement in the patient's condition or lack of reduction in the risk of cardiovascular death [4,18]. Moreover, iron overload by supplementation is toxic to the organism.…”

“…Systemic ID is associated with reduced exercise tolerance, increased symptom severity and higher mortality rates independent of coexisting anemia. Randomized clinical trials have shown that in the case of ID, intravenous iron supplementation improves symptoms, exercise capacity and quality of life in ambulatory patients with chronic HF [3,4]. Very recently, Ponikowski et al showed that in patients with ID who were stabilized after an episode of acute HF, iv.…”

Systematic review and meta‐analysis of intravenous iron‐carbohydrate complexes in HFrEF patients with iron deficiency

“…A more recent meta‐analysis conducted by Yamani et al . 30 separately examined oral and IV iron supplementation and found that IV iron‐carbohydrate supplementation significantly reduced overall and HF hospitalizations compared with control. Consistent with these previous meta‐analyses, the present study found that IV iron‐carbohydrate therapy reduced the rates of hospitalization for worsening HF and also first hospitalization for worsening HF or death, but did not significantly alter the rate of all‐cause mortality.…”

“…of RCTs including patients with HF, regardless of LVEF, found that iron supplementation (oral or IV) improved HF hospitalization rates, cardiac function, and QoL, but did not impact on mortality rates. A more recent meta‐analysis conducted by Yamani et al 30 . separately examined oral and IV iron supplementation and found that IV iron‐carbohydrate supplementation significantly reduced overall and HF hospitalizations compared with control.…”