Intravenous Iron Supplementation Research Articles

Background: Iron deficiency is a common comorbidity in patients with pulmonary hypertension (PH), affecting approximately 43–60% of this population. Iron plays a crucial role in oxygen transport and cellular energy metabolism, and its deficiency has been associated with impaired exercise tolerance and worse clinical outcomes. While intravenous iron supplementation, has shown promise in improving functional parameters in heart failure, its role in PH remains less well defined. A systematic synthesis of the evidence is warranted to better understand the potential therapeutic value of iron supplementation in this high-risk population. Hypothesis: Our hypothesis proposes that iron supplementation may significantly improve functional outcomes in PH patients with documented iron deficiency. Methods: We conducted a systematic review and meta-analysis to evaluate the effect of iron supplementation on the functional capacity in adults with PH. We used PubMed, MEDLINE and EMBASE for our systematic search of relevant studies published between 2014-2024. The studies reported a change in functional capacity with a 6-minute walk test (6MWT) distance. To assess study quality, we used the Newcastle- Ottawa Scale for observational studies and Jadad score for randomized controlled trials (RCTs). Using random-effects models, we calculated the mean differences with a 95% confidence interval. Results: From the collected studies, nine studies met the inclusion criteria (Figure 1). The pooled effect showed a significant improvement in 6MWT distance following iron supplementation (28.64 meters; 95% CI: 16.64 to 40.64; p < 0.01) with a substantial heterogeneity (78.5%) (Figure 2) . Of the studies considered, high-quality RCTs displayed smaller, non-significant changes (10.65 meters; 95% CI: -10.81 to 32.11) and non-randomized studies showed larger effects on functional capacity (31.68 meters; 95% CI: 21.90 to 41.45) (Figure 3). Improvements were more evident in patients with anemia at baseline. Conclusions: Iron supplementation may improve functional capacity in patients with pulmonary hypertension, particularly those with anemia. However, heterogeneity, potential bias, and differences between randomized and non-randomized studies limit the strength of current evidence. Well-designed, adequately powered trials are needed to clarify the clinical benefits and underlying mechanisms. Until then, iron therapy should be considered on a case-by-case basis.

Cognitive dysfunction after successful heart transplantation (HTx) is not uncommon. Lower hemoglobin levels have previously been associated with cognitive dysfunction in heart transplant recipients (HTx recipients). In a randomized, placebo-controlled, double-blind treatment trial, we assessed as a pre-specified secondary outcome whether a single intravenous iron supplement for iron deficiency in HTx recipients resulted in changes in cognitive function after 6 months. In the "Intravenous Iron Supplement for Iron Deficiency in Cardiac Transplant Recipients" (IronIC) trial, we assessed cognitive function at baseline and at 6-month follow-up with the following tests of the Cambridge Neuropsychological Test Automated Battery: Reaction Time, Paired Associates Learning, and Spatial Working Memory. Of 94 participants with cognitive data at baseline and follow-up, 49 were randomized to the single intravenous iron supplement, while 45 received placebo. Raw score changes from baseline to follow-up did not differ statistically significantly between study groups (two measures of each test analyzed). In the total sample, 27%-44% of participants performed at baseline at least one standard deviation below the normative mean on measures of memory and working memory/executive functions. Exploratory analyses indicated that performance on measures of memory might decrease more than expected with increasing age. A single intravenous iron supplement for iron deficiency in HTx recipients did not result in statistically significant cognitive changes after 6 months. The group as a whole performed approximately half a standard deviation below the normative mean on measures of memory and working memory/executive functions. Regular cognitive screening after HTx is recommended. Trial Registration: ClinicalTrials.gov identifier: NCT03662789.

Anaesthetic Considerations for Patient Blood Management in Cancer Surgery: A Narrative Review.

Heart failure (HF) is a chronic and progressive condition associated with significant morbidity and mortality and reduced quality of life. Among the various comorbidities that exacerbate HF outcomes, iron deficiency (ID) is increasingly recognized as a modifiable risk factor that contributes to decreased exercise capacity, fatigue, and hospitalizations, even in the absence of anemia. Approximately 30-50% of patients with HF present with ID, highlighting the need for routine screening and targeted management. The objective of this review was to summarize the pathophysiological basis, diagnostic criteria, and clinical implications of ID in HF and to provide evidence-based recommendations for its treatment based on current guidelines and clinical trials. Key clinical trials such as FAIR-HF, CONFIRM-HF, and AFFIRM-AHF have demonstrated that intravenous iron supplementation, particularly with ferric carboxymaltose, improves functional status, symptoms, and quality of life in patients with HF and ID. These benefits are observed irrespective of the presence of anemia, and treatment is associated with a favorable safety profile. Current guidelines recommend routine screening for ID in patients with chronic HF and consideration of intravenous iron supplementation in symptomatic patients with confirmed deficiency. Oral iron has shown limited efficacy in this population. In conclusion, ID is a treatable and impactful comorbidity in HF. Early detection and appropriate intravenous iron therapy can significantly improve patient-centered outcomes and should be incorporated into standard HF management strategies.

BackgroundWhile intravenous iron improves outcomes in anaemic surgical patients, the impact of iron deficiency (ID) and its treatment in non-anaemic patients remains unclear.MethodsIn this single-centre retrospective analysis, non-anaemic ID patients (age ≥ 18 years) undergoing major cardiac surgery at the University Hospital Frankfurt were included. Primary endpoints were red blood cell (RBC) transfusion rate and use of RBC units. Secondary endpoints were increase in haemoglobin levels and postoperative outcome (mortality, length of stay, mechanical ventilation, laboratory values). Patients were assigned to the following groups: No-Iron (no anaemia, ID, and no iron supplementation) and Iron (anaemia, ID, and iron supplementation).ResultsA total of 3605 patients were screened, of whom 2345 were non-anaemic. Six hundred ninety-eight non-anaemic ID patients were included in the analysis, of whom 90 received intravenous iron supplementation. The overall RBC transfusion rate (43.6% [95% CI: 39.6–47.6] versus 50.0% [95% CI: 39.9–60.1]) and number of transfused blood units (2.0 [IQR: 1.0; 4.0] versus 2.0 [IQR: 1.0; 4.0]) were similar between patients of the No-Iron and Iron groups. Hospital length of stay, mortality, and postoperative complications were similar in both groups. When applying stricter cutoff values to define ID (ferritin < 30 μg/l), a trend toward reduced transfusion rates was observed: total RBC transfusion rate was 50.0% (95% CI: 34.9–65.2) in the No-Iron group and 42.9% (95% CI: 26.8–60.5) in the Iron group. In the case of short-term (1 day prior to surgery) iron supplementation, RBC unit utilisation and postoperative outcomes were comparable between the two groups.ConclusionIn non-anaemic cardiac surgery patients, (short-term) preoperative intravenous iron supplementation showed no significant impact on RBC transfusion rate, haemoglobin levels, or postoperative outcomes. However, a stricter definition of ID revealed a trend toward reduced transfusion rates.Supplementary InformationThe online version contains supplementary material available at 10.1186/s13741-025-00596-8.

The treatment of heart failure varies depending on left ventricular ejection fraction (LVEF) and poses asignificant clinical challenge in patients with reduced (HFrEF), mildly reduced (HFmrEF), or preserved ejection fraction (HFpEF). In HFrEF/HFmrEF, the diagnosis is based on clinical symptoms such as dyspnea or peripheral edema, as well as an LVEF < 50%. Treatment primarily relies on renin-angiotensin system (RAS) inhibitors (preferably angiotensin receptor-neprilysin-inhibitors, ARNIs), beta-blockers, mineralocorticoid receptor antagonists (MRAs), and sodium-glucose co-transporter 2inhibitors (SGLT2i). These agents have aclassI recommendation and significantly reduce both mortality and hospitalization rates. Rapid and comprehensive implementation of this therapeutic strategy substantially improves prognosis. Additional agents such as ivabradine or vericiguat can be considered. With the recent publication of the DIGIT-HF study, evidence now also supports the use of digitoxin in advanced HFrEF to further reduce mortality and hospitalizations. Iron deficiency is common in HFrEF and is associated with worse outcomes. Intravenous iron supplementation improves exercise capacity and reduces the risk of hospitalization especially after adecompensation. In patients with HFpEF, treatment focuses on symptomatic relief and rigorous management of comorbidities. Diuretics for volume overload have aclassI recommendation, as they effectively alleviate symptoms. SGLT2i also play akey role in HFpEF and are recommended with classI evidence in current guidelines. FINEARTS-HF recently showed promising results for the non-steroidal MRA finerenone, which reduces cardiovascular death/hospitalizations. Furthermore, metabolically targeted therapies such as GLP‑1 receptor agonists are gaining importance in obese HFpEF patients, as they have been shown to improve quality of life and reduce heart failure-related events.

Ferumoxytol-Enhanced Cardiovascular Magnetic Resonance Imaging: Applications and Technical Advances.

Inflammation-Driven Differential Response to Intravenous vs. Oral Iron Supplementation in Patients on Hemodialysis: Post Hoc Analysis of the IHOPE Trial

Background: Iron deficiency (ID) is a frequent comorbidity in heart failure (HF), associated with reduced functional capacity and poor prognosis. Although the European Society of Cardiology (ESC) guidelines recommend systematic screening and intravenous iron supplementation (IS), adherence in clinical practice remains limited. This observational study aimed to evaluate how these recommendations are implemented into practice. Methods: We performed a retrospective study including 4348 patients hospitalized with HF (NYHA II-IV) in a tertiary internal medicine clinic in Eastern Europe between January 2018 and September 2022. Demographic data, comorbidities, laboratory parameters, echocardiographic findings were collected from electronic medical records. IS was defined as serum ferritin < 100 ng/mL. Results: Among HF patients, 2547 (58.7%) were screened for ID, and 1091 (42.8%) had absolute deficiency. Only 278 patients (25.5%) received intravenous ferric carbodymaltose. Treated patients were predominantly elderly (70.1% ≥ 70 years), female (60.4%), and often had ischemic or valvular disease. Patients receiving intravenous IS showed higher NT-proBNP and troponin levels. A progressive increase in IS use was observed during the study period, with a temporary decline during the COVID-19 pandemic. Conclusions: Despite relatively high screening rates, only one-quarter of HF patients with confirmed ID received intravenous IS. These findings highlight persistent gaps between guidelines and clinical practice, emphasizing the need for improved awareness and implementation of ESC recommendations to optimize outcomes in HF patients with ID.

Anemia in cardiorenal disease: From pathogenesis to treatment.

Introduction: Anemia is common in hemodialysis patients, and iron supplementation is essential for its management. However, the impact of baseline inflammation on the efficacy of oral versus intravenous iron remains unclear. Methods: This post hoc analysis of the IHOPE trial included 193 maintenance hemodialysis patients stratified by median baseline high-sensitivity C-reactive protein (hsCRP). Patients were randomized to receive intravenous iron sucrose (100 mg once biweekly) or oral polysaccharide-iron complex (150 mg twice daily) for 24 weeks. The primary outcome was hemoglobin level at 24 weeks. Secondary outcomes included hsCRP, oxidative stress markers, and iron parameters. Results: At 24 weeks, patients with high baseline hsCRP had lower hemoglobin levels than those with low hsCRP (113.82 ± 12.04 vs. 118.05 ± 13.50 g/L, p = 0.038), despite similar baseline hemoglobin values. Among patients receiving intravenous iron sucrose, those with high hsCRP had significantly lower hemoglobin (112.90 ± 13.19 vs. 121.32 ± 13.46 g/L; p = 0.005) and higher hsCRP and superoxide dismutase levels, suggesting persistent inflammation and oxidative stress. In contrast, hemoglobin levels were similar between high and low hsCRP subgroups in the oral polysaccharide-iron complex group (p = 0.913). Iron parameters and adverse events were comparable across groups. Conclusion: This post hoc analysis suggests baseline inflammation significantly modifies responses to specific iron formulations in hemodialysis patients. Patients with elevated hsCRP showed poorer hemoglobin responses to intravenous iron sucrose, while oral polysaccharide-iron complex maintained consistent efficacy across inflammatory states. These findings warrant prospective studies on inflammation-guided personalization of iron therapy.

Anaemia in cancer patients: Advances and challenges in the era of precision oncology.

The impact of intravenous iron therapy in heart failure (HF) patients with iron deficiency (ID) is still controversial. We performed an extensive search of electronic databases for pertinent studies, encompassing all records up to March 4, 2024. Using random-effects models in a meta-analysis, the collected outcomes data were then synthesized and analyzed. Fourteen trials with 7786 participants (iron therapy: n = 3994; control: n = 3792) were included. Intravenous iron therapy can decrease the risk of composite events of total hospitalization for HF and cardiovascular (CV) death (RR = 0.82 [0.72, 0.92]), total hospitalization for HF (RR = 0.78 [0.66, 0.91]), first hospitalization for HF and CV death (OR = 0.78 [0.65, 0.93]), CV death (OR = 0.86 [0.76, 0.98]), first hospitalization for HF(OR = 0.77 [0.61, 0.99]), but not significantly reduce the risk of all-cause mortality (OR = 0.93 [0.83, 1.04]). Furthermore, intravenous iron treatment can improve the distance of 6-min walking test (6MWT) (WMD = 18.99 [7.41, 30.57]). Subgroup analyses found that intravenous iron may be more beneficial in HF patients with transferrin saturation (TSAT) <20%, and those with ischemic heart disease. Meta-regression analysis revealed that baseline hemoglobin levels served as a significant moderator of the therapeutic efficacy of intravenous iron supplementation. For HF patients with ID, intravenous iron therapy can decrease the risk of hospitalization for HF, CV death and improve their exercise capacity. Patients with ischemic cardiomyopathy or with TSAT <20% may derive greater benefit from intravenous iron therapy.

Intravenous Ferric Carboxymaltose in Ischemic Versus Non-Ischemic Heart Failure and Iron Deficiency: Insights From FAIR-HF2.

Evaluating ferric carboxymaltose administration in elderly patients: Clinical outcomes, comparative characteristics in different care settings and cost analysis. A five year study.

Altitude may influence the requirement for erythropoiesis-stimulating agent (ESA) therapy in patients undergoing hemodialysis (HD). This study aimed to compare anemia-related parameters, ESA utilization, and intravenous (IV) iron supplementation among HD patients residing at different altitudes. This retrospective-multicenter study was conducted in three provinces of Türkiye, each located at a distinct altitude: Balikesir (139 m; low-altitude-group [LA]), Malatya (964 m; moderate-altitude-group [MA]), and Hakkari (1728 m; high-altitude-group[HA]). Two hundred and twenty nine HD patients were included in the study: 99 in the LA group, 77 in the MA group, and 53 in the HA group. The mean age was 59 ± 13 years. ESA use was observed in 92 (93%) patients in the LA group, 61 (73%) in the MA group, and 43 (81%) in the HA group (p = 0.021). Age (OR: 1.102, 95% CI: 1.035-1.174, p = 0.003), female gender (OR: 6.068, 95% CI: 1.080-34.111, p = 0.041), residing at LA (OR: 12.845, 95% CI: 1.833-90.118, p = 0.010), IV iron use (OR: 21.015, 95% CI: 3.397-130.009, p = 0.001), hematocrit (OR: 0.364, 95% CI: 0.229-0.578, p < 0.001), and ferritin (OR: 1.003, 95% CI: 1.001-1.005, p = 0.007) were identified as independent predictors of ESA use. Residing at LA was associated with increased ESA requirements in HD patients, suggesting that altitude may be a relevant factor in anemia management.

Blood transfusion mediated tumor microenvironment remodeling in breast cancer.

Intravenous iron supplementation, particularly ferric carboxymaltose (FCM), has emerged as an effective therapeutic strategy for correcting iron deficiency (ID) in patients with heart failure with reduced ejection fraction (HFrEF). However, the enhancement related to the quality of life (QoL) and functional capacity remains unclear, specifically in the Vietnam population. This study assesses the enhancement of QoL and functional capacity in intravenous FCM therapy in heart failure patients with ID. We conducted a cross-sectional analysis study in patients with chronic HFrEF. Eligible patients diagnosed with ID were treated with FCM. Endpoint was the improvement in QoL, assessed by the European Quality of Life 5 Dimensions 5 Level Version questionnaire, and functional capacity, measured by the change in the 6-minute walk test and New York Heart Association Functional Classification. A total of 132 patients with chronic HFrEF, with 35.60% of patients with ID. The study population had a mean age of 65.7 ± 9.4 years, males accounted for 56.8%. Female, New York Heart Association ≥3 and poor QoL significantly associated with ID. Notably, 12 weeks after intervention, patients with poor QoL decreased from 48.9% to 34.0% (P < .001). Functional capacity, assessed by the 6-minute walk test, improved with the median distance increasing from 239.90 (198.80–291.70) m at baseline to 262.60 (219.50–309.70) m (P < .01). Nausea was reported by a small minority at 4.25%. Our study highlights the significant burden of ID in patients with HFrEF, emphasizing its strong association with symptom severity, functional impairment, and reduced QoL. Intravenous FCM therapy demonstrated significant improvements in iron parameters, functional capacity, and QoL, with a favorable safety profile.

Intravenous iron has emerged as a guideline-recommended therapy in patients with heart failure and iron deficiency, but the potential sex-related differences in efficacy are unknown. We aimed to assess sex-specific outcomes in the Intravenous Iron in Patients with Systolic Heart Failure and Iron Deficiency to Improve Morbidity & Mortality (FAIR-HF2-DZHK05) trial. FAIR-HF2 included 1105 heart failure patients with a left ventricular ejection fraction ≤45% and iron deficiency. A total of 368 women (mean age 68.7 ± 13.0 years) and 737 men (mean age 70.5 ± 11.0 years) were randomized to intravenous ferric carboxymaltose or placebo. The three primary endpoints were (i) time to cardiovascular death or first heart failure hospitalization, (ii) total heart failure hospitalizations, and (iii) time-to-first event of cardiovascular death or heart failure hospitalization only in patients with transferrin saturation <20% at baseline. The hazard ratio (HR) for the first primary outcome was 1.07 (95% confidence interval [CI] 0.63-1.82, p = 0.80) in women and 0.74 (95% CI 0.57-0.95, p = 0.016) in men, while the rate ratios (RRs) for the second primary outcome were 1.06 (95% CI 0.55-2.05, p = 0.86) and 0.79 (95% CI 0.58-1.08, p = 0.136), respectively, and the HRs for the third primary outcome event were 1.21 (95% CI 0.62-2.36, p = 0.58) and 0.73 (95% CI 0.55-0.97, p = 0.028), respectively. Regarding safety outcomes, the HR for all-cause mortality was 1.46 (95% CI 0.78-2.76, p = 0.24) in women, suggesting increased mortality risk under iron supplementation, in contrast to 0.86 (95% CI 0.64-1.16, p = 0.33) in men (p for interaction = 0.13). This analysis indicates relevant differential efficacy of intravenous iron in heart failure across both sexes. While men receiving ferric carboxymaltose experienced a clinically relevant reduction in cardiovascular death and heart failure hospitalizations, women did not derive similar benefits. The results are clinically relevant and prompt validation in other large outcome trials of intravenous iron supplementation in heart failure. ClinicalTrials.gov NCT03036462.

Iron deficiency anaemia (IDA) is one of the most prevalent and clinically significant complications of chronic kidney disease (CKD), contributing to increased morbidity, reduced quality of life, and accelerated disease progression. The pathogenesis of IDA in CKD is multifactorial, involving absolute or functional iron deficiency, inflammation-mediated disruptions in iron homeostasis, and diminished erythropoietin production by the diseased kidneys. Elevated hepcidin levels further exacerbate iron sequestration, impairing erythropoiesis. Effective management of IDA in CKD focuses on replenishing iron stores, optimizing haemoglobin levels, enhancing the efficacy of erythropoiesis-stimulating agents (ESAs), minimizing blood transfusions, and improving patient quality of life. Pharmacological interventions include oral and intravenous iron supplementation, ESAs, and novel agents such as hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs), ferric pyrophosphate citrate (FPC), and liposomal iron formulations. Emerging therapies targeting hepcidin pathways and erythroferrone analogs offer promising avenues to address treatment limitations, especially ESA resistance and inflammation-associated anaemia. Despite these advances, therapeutic challenges persist, underscoring the need for individualized, multidisciplinary approaches and continued research into innovative therapies for IDA in CKD.