Intravenous Ferric Carboxymaltose Research Articles

Randomized Controlled Trial of Intravenous Ferric Carboxymaltose vs Oral Iron to Treat Iron Deficiency Anemia After Variceal Bleed in Patients With Cirrhosis.

Limited evidence exists on the optimal strategy to correct iron deficiency anemia after variceal bleeding (VB) in cirrhosis. This trial compared the efficacy and safety of intravenous ferric carboxymaltose (IV-FCM) with those of oral iron therapy in this cohort. In this open-label, single-center, randomized controlled trial, eligible patients with hemoglobin <10 g/dL and iron deficiency (ferritin <100 ng/mL) after VB received either IV-FCM (1,500-2,000 mg) divided into 2 doses (n = 48) or oral carbonyl iron (100 mg elemental iron/day) (n = 44) for 3 months. The primary outcome was change in hemoglobin at 3 months. Secondary outcomes included improvement in anemia (last hemoglobin >12 g/dL), normalization of iron stores (ferritin >100 ng/mL), liver-related adverse events, adverse drug reactions, and changes in quality of life (CLDQOL questionnaire). Baseline characteristics, including median Child-Turcotte-Pugh score 7 (interquartile range [IQR] 6-9), Model for End-Stage Liver Disease score 12 (IQR 10-17), blood hemoglobin (8.25 ± 1.06 g/dL), and ferritin (30.00 ng/mL [15.00-66.50]), were comparable in both arms. The median increase in hemoglobin at 3 months in the IV and oral arms was 3.65 g/dL (IQR 2.55-5.25) and 1.10 g/dL (IQR 0.05-2.90 g/dL) ( P < 0.001), respectively. Iron stores normalized in 84.6% and 21% of the IV and oral arms, respectively ( P < 0.001). Anemia improved in 50% and 21.9% in the IV and oral arms, respectively ( P < 0.009). Patients in the IV arm showed a significant improvement in all domains of CLDQOL. Liver-related adverse events were comparable in both arms. Transient mild/moderate hypophosphatemia developed in 43% of patients receiving IV-FCM. Intravenous iron replacement is efficacious and safe to treat iron deficiency anemia after VB in patients with cirrhosis.

Intravenous iron supplementation improves energy metabolism of exercising skeletal muscles without effect on either oxidative stress or inflammation in male patients with heart failure with reduced ejection fraction.

Skeletal muscle dysfunction is a feature of heart failure (HF). Iron deficiency (ID) is prevalent in patients with HF associated with exercise intolerance and poor quality of life. Intravenous iron in iron deficient patients with HF has attenuated HF symptoms, however the pathomechanisms remain unclear. The aim of study was to assess whether intravenous iron supplementation as compared to placebo improves energy metabolism of skeletal muscles in patients with HF. Men with heart failure with reduced ejection fraction (HFrEF) and ID were randomised in 1:1 ratio to either intravenous ferric carboxymaltose (IV FCM) or placebo. In vivo reduction of lactates by exercising skeletal muscles of forearm was analyzed. A change in lactate production between week 0 and 24 was considered as a primary endpoint of the study. There were two study arms: the placebo and the IV FCM (12 and 11 male patients with HFrEF). At baseline, there were no differences between these two study arms. IV FCM therapy as compared to placebo reduced the exertional production of lactates in exercising skeletal muscles. These effects were accompanied by a significant increase in both serum ferritin and transferrin saturation in the IV FCM arm which was not demonstrated in the placebo arm. Intravenous iron supplementation in iron deficient men with HFrEF improves the functioning of skeletal muscles via an improvement in energy metabolism in exercising skeletal muscles, limiting the contribution of anaerobic reactions generating ATP as reflected by a lower in vivo lactate production in exercising muscles in patients with repleted iron stores.

Clinical Efficacy and Safety of Intravenous Ferric Carboxymaltose for Treatment of Restless Legs Syndrome: A Multicenter, Randomized, Placebo-controlled Clinical Trial.

Iron therapy is associated with improvements in restless legs syndrome (RLS). This multicenter, randomized, double-blind study evaluated the effect of intravenous ferric carboxymaltose (FCM) on RLS. A total of 209 adult patients with a baseline International Restless Legs Syndrome (IRLS) score ≥15 were randomized (1:1) to FCM (750mg/15mL) or placebo on study Days 0 and 5. Ongoing RLS medication was tapered starting on Day 5, with the goal of discontinuing treatment or achieving the lowest effective dose. Co-primary efficacy endpoints were change from baseline in IRLS total score and the proportion of patients rated as much/very much improved on the Clinical Global Impression-investigator (CGI-I) scale at Day 42 in the "As-Treated" population. The "As-Treated" population comprised 107 FCM and 101 placebo recipients; 88 (82.2%) and 68 (67.3%), respectively, completed the Day 42 assessment. The IRLS score reduction was significantly greater with FCM versus placebo: least-squares mean (95% confidence interval [CI]) -8.0 (-9.5, -6.4) versus -4.8 (-6.4, -3.1); P = 0.0036. No significant difference was observed in the proportion of FCM (35.5%) and placebo (28.7%) recipients with a CGI-I response (odds ratio 1.37 [95% CI: 0.76, 2.47]; P = 0.2987). Fewer patients treated with FCM (32.7%) than placebo (59.4%) received RLS interventions between Day 5 and study end (P = 0.0002). FCM was well tolerated. The IRLS score improved with intravenous FCM versus placebo, although the combination of both co-primary endpoints was not met. Potential methodological problems in the study design are discussed.

A comparative study of ferric carboxymaltose and iron sucrose as a parenteral iron treatment in iron deficiency anemia during pregnancy in a tertiary care hospital

Background: Anemia from the Greek word (anhaima) meaning “without blood” is the deficiency of red blood cell and/or hemoglobin which result in reduced oxygen-carrying capacity of blood causing tissue hypoxia. Aims and Objectives: To study the efficacy and safety of intravenous ferric carboxymaltose (FCM) versus iron sucrose in the management of iron deficiency anemia in pregnancy. Materials and Methods: A prospective, single-center, comparative interventional randomized study was carried among 180 antenatal mother admitted to antenatal ward in the Department of Obstetrics and Gynaecology of Burdwan Medical College and Hospital, from July 1st, 2020, to December 30th, 2021. Results: A total of 180 patients, 90 patients in each FCM and iron sucrose group, were included in the study. There was significant (P=0.001) mean change in hemoglobin (Hb) level in both the groups from pre-treatment to 3 and 6-week post-treatment. There was also a significant (P=0.001) mean change in ferritin level in both the groups from pre-treatment to 3 and 6-week post-treatment. The mean change in Hb level and ferritin level was higher among patients of FCM compared to iron sucrose. The adverse reactions were lower among patients of FCM than iron sucrose. Conclusions: This study found that FCM is safer than iron sucrose. Treatment with FCM resulted in rapid replenishment of iron stores in pregnant women with significantly high rise of Hb and ferritin levels over a 6-week period with lesser adverse effects.

Retrospective Study Comparing Treatment Outcomes in Obstetric Patients With Iron Deficiency Anemia Treated With and Without Intravenous Ferric Carboxymaltose.

Introduction Iron deficiency anemia is associated with an increased risk of adverse maternal and perinatal outcomes. Intravenous iron preparation containing ferric carboxymaltose has been shown to be a safe and effective way of increasing hemoglobin (Hb) and mean corpuscular volume (MCV) levels and reducing the need for blood transfusion. In our center, it used to be given as an inpatient procedure because of the risks of potential drug reactions. In 2021, we initiated the administration of intravenous ferric carboxymaltose as an outpatient procedure. We compared the outcomes of patients between 2021 and 2023 after the initiation of outpatient administration of intravenous ferric carboxymaltose in 127 obstetric patients with iron deficiency anemia in the second and third trimesters. Methods In this study conducted in a large maternity unit in Singapore between 2021 to 2023, we compared the changes in maternal hematological parameters among obstetric patients with iron deficiency anemia presenting to the day care unit in the second or third trimester with a Hb level of <8 g/dl treated with a single dose of ferric carboxymaltose injection (Ferinject) against a control group who were referred for treatment but defaulted on and declined treatment. Results Ferric carboxymaltose significantly increased the Hb and MCV levels at delivery in obstetric patients with iron deficiency. The mean Hb at delivery was 10.8 g/dL in the case group compared to 8.8 g/dL in the control group. The percentage of patients with Hb ≥10.0 g/dL was 73.4% in the case group compared to 27.8% in the control group. The incidence of adverse side effects was low and mild (2/127; 1.6%). None of the patients received were hospitalized because of ferric carboxymaltose. Conclusion A single injection dose of ferric carboxymaltose as an outpatient antenatal procedure was easily administered and well tolerated. Obstetric patients with iron deficiency anemia who received intravenous ferric carboxymaltose had a significantly higher level of Hb than those who did not.

The Impact of Intravenous Ferric Carboxymaltose on Reverse Electrical Remodeling Following Cardiac Resynchronization Therapy.

The influence of intravenous ferric carboxymaltose (FCM) on reverse electrical remodeling (RER) in patients with heart failure with reduced ejection fraction (HFrEF) post-cardiac resynchronization therapy (CRT) is unknown. This study examines the effect of iron replacement using intravenous FCM on RER in CRT-implanted HFrEF patients with iron deficiency anemia. We retrospectively analyzed 65 patients with successful CRT-defibrillator between March 2017 and January 2020, all with iron deficiency anemia at implantation. The cohort comprised 35 patients in the FCM group and 30 in the non-FCM group. Follow-up data were obtained from visits 6 months post-CRT implantation including baseline characteristics, echocardiographic left ventricular measurements, and electrocardiograms. Changes in intrinsic QRS duration (iQRS) and left ventricular ejection fraction (LVEF) from baseline to 6 months were assessed. The FCM group showed a greater reduction in iQRS duration compared to the non-FCM group (-10.4 ± 2.2 ms vs. -3 ± 2.9 ms, p < 0.0001). Additionally, at the 6-month follow-up, the increase in LVEF was higher in the FCM group than in the non-FCM group (+3.6 ± 1.6% vs. -0.1 ± 1.7%, p < 0.0001). Correlations were found between changes in ferritin levels and iQRS duration (r = -0.725, p < 0.0001) and LVEF (r = 0.712, p < 0.0001). Multivariate regression analysis revealed that elevated ferritin independently influenced the increase in LVEF (p = 0.006, β = 0.554) and the decrease in iQRS (p < 0.001, β = -0.685). Intravenous iron treatment with FCM may reduce iQRS duration and improve LVEF and functional status in HFrEF patients with iron deficiency anemia following CRT.

Benefits of intravenous iron supplementation in heart failure.

Introduction: Iron deficiency (ID) is one of the most frequent comorbidities in patients with heart failure (HF) and is estimated to be present in up to 80% of acute patients regardless of their ejection fraction. Randomized controlled trials have shown that supplementary intravenous iron results in improved clinical outcomes; however, the current understanding of the effects of intravenous iron on morbidity and mortality remains limited. Study and results: The meta-analysis pooled individual participant data from three randomized placebo-controlled trials of ferric carboxymaltose (FCM) in adult patients (n = 4,501) with heart failure and iron deficiency (CONFIRM-HF, AFFIRM-AHF, and HEART-FID). FCM therapy significantly reduced the co-primary composite endpoint of total cardiovascular hospitalizations and cardiovascular death, with a rate ratio (RR 0.86; 95% CI 0.75 to 0.98; p = 0.029). FCM therapy was associated with a 17% relative rate reduction in total cardiovascular hospitalizations (RR 0.83; 95% CI 0.73 to 0.96; p = 0.009) and a 16% relative rate reduction in total heart failure hospitalizations (RR 0.84; 95% CI 0.71 to 0.98; p = 0.025). Lessons learned: The meta-analysis shows that in iron-deficient patients with heart failure and reduced or mildly reduced left ventricular ejection fraction, intravenous ferric carboxymaltose (FCM) is associated with a reduced risk of total cardiovascular hospitalization and cardiovascular mortality. These findings indicate that intravenous FCM should be considered in iron-deficient patients with heart failure and reduced or mildly reduced ejection fractions.

Maternal Fatigue after Postpartum Anemia Treatment with Intravenous Ferric Carboxymaltose vs. Intravenous Ferric Derisomaltose vs. Oral Ferrous Sulphate: A Randomized Controlled Trial

(1) Background: Postpartum anemia is a common maternal complication and is recognized as a cause of impaired quality of life, reduced cognitive abilities, and fatigue. Efficient iron supplementation for the treatment of postpartum anemia is an essential component of high-quality maternal care. The optimal mode of iron supplementation has not been determined yet, whether oral or intravenous. The objective of this study was to compare postpartum anemia treatment with intravenous ferric carboxymaltose, intravenous ferric derisomaltose, and oral ferrous sulfate. (2) Methods: A single-center, open-label, randomized controlled trial. Women with hemoglobin &lt; 100 g/L within 48 h postpartum were randomly allocated to receive intravenous ferric carboxymaltose, intravenous ferric derisomaltose, or oral ferrous sulfate. Intravenous iron was given in one or two doses, while ferrous sulfate was given as two 80 mg tablets once daily. The primary outcome was maternal fatigue measured by the Multidimensional Fatigue Inventory (MFI) six weeks postpartum. Hemoglobin, ferritin, and transferrin saturation levels were analyzed as secondary outcomes. A Kruskal–Wallis test was used for group comparison (p &lt; 0.05 significant). (3) Results: Three hundred women were included. The MFI score at six weeks postpartum did not differ between groups (median 38 (inter-quartile range (IQR) 29–47) in the ferric carboxymaltose group, median 34 (IQR 26–42) in the ferric derisomaltose group, and median 36 (IQR 25–47) in the ferrous sulfate group; p = 0.26). Participants receiving oral iron had lower levels of hemoglobin (135 (131–139) vs. 134 (129–139) vs. 131 (125–137) g/L; p = 0.008), ferritin (273 (198–377) vs. 187 (155–246) vs. 24 (17–37) µg/L; p &lt; 0.001) and transferrin saturation (34 (28–38) vs. 30 (23–37) vs. 24 (17–37) %; p &lt; 0.001) than those receiving ferric carboxymaltose or ferric derisomaltose. (4) Conclusions: Intravenous ferric carboxymaltose, intravenous ferric derisomaltose, and oral ferrous sulfate had similar impacts on maternal fatigue at six weeks postpartum despite improved laboratory parameters in the intravenous groups.

Clinical effectiveness of ferric carboxymaltose (iv) versus iron sucrose (iv) in treatment of iron deficiency anaemia in pregnancy: A systematic review and meta-analysis.

Iron deficiency anaemia (IDA) during pregnancy is treated with oral and parenteral iron. The objective of this review was to compare the clinical effectiveness, safety, pregnancy and neonatal outcomes of intravenous (iv) ferric carboxymaltose (FCM) and iv iron sucrose (IS) in treating IDA in pregnancy. The Department of Health Research funded this study. PubMed, Cochrane Library, EMBASE and Scopus were searched to include studies published till November 2022. The protocol was registered in PROSPERO (CRD42022306092). Pregnant women (15-49 yr) in second and third trimesters, diagnosed with moderate-to-severe iron deficiency anaemia, treated with either of the drugs were included. The included studies were critically assessed using appropriate tools. We conducted a qualitative synthesis of the studies and meta-analysis for improvement in haematological parameters and incidence of adverse events. A total of 18 studies were included. The risk of bias was low to moderate. A rise in haemoglobin up to four weeks was higher with FCM than IS by 0.57 (0.24, 0.9) g/dl. Intravenous FCM is associated with fewer adverse events than IS [pooled odds ratio: 0.5 (0.32, 0.79)]. The included studies had limited evidence on pregnancy and neonatal outcomes after iv iron treatment. Intravenous FCM is effective and safer than intravenous IS in terms of haematological parameters, in treating IDA in pregnancy. Further research is required on the effects of iv FCM and iv IS on the pregnancy and neonatal outcomes when used for treating IDA in pregnancy.

Demir Eksikliği Anemili Kadın Hastalarda İntravenöz Demir Tedavisinin Etkinliği

Abstract: In this study, it was aimed to show the efficacy of intravenous (IV) ferric carboxymaltose treatment for iron deficiency anemia (IDA), which is a public health problem due to its high prevalence in the world and in Turkey. Since it is the first study in the region, its importance is increasing even more. Eighty female diagnosed with IDA and treated with IV iron carboxymaltose, who applied to Siirt Training and Research Hospital Internal Diseases Polyclinics between June 2018 and September 2019, were included in the study. After obtaining voluntary consent of female patients, biochemical data of pre- and post-treatment were included in the study retrospectively. After treatment, hemoglobin (HGB), hematocrit (HTC), mean cell volume (MCV), ferritin, iron and B12 values increased statistically (p

Iron deficiency in heart failure with preserved ejection fraction: rationale and design of the FAIR-HFpEF trial

Background: Iron deficiency is highly prevalent in patients with heart failure and has well established diagnostic criteria. Its occurrence is associated with reduced quality of life, exercise capacity and increased hospitalization rates and mortality. The clinical efficacy of treating iron deficiency has not been tested in patients with heart failure with preserved ejection fraction (HFpEF). Methods: The FAIRHFpEF trial aims to enroll patients with HFpEF, reduced exercise capacity and iron deficiency (defined as serum ferritin &lt;100 ng/mL or serum ferritin 100299 ng/mL with transferrin saturation &lt;20%). Patients will be treated in a multicenter, doubleblind, randomized clinical trial with intravenous ferric carboxymaltose (FCM) at doses aimed to replenish iron stores vs. placebo. The primary endpoint is the difference in exercise capacity from baseline to week 24 as assessed by the 6minute walk test. Secondary endpoints include healthrelated quality of life assessments such as the Kansas City Cardiomyopathy Questionnaire, the European Quality of Life5 Dimensions questionnaire and global function tests. Conclusions: The FAIRHFpEF trial is designed to investigate the effect of intravenous iron repletion in iron deficient patients with HFpEF using FCM.

Iron deficiency in heart failure with preserved ejection fraction: rationale and design of the FAIR-HFpEF trial

Background: Iron deficiency is highly prevalent in patients with heart failure and has well established diagnostic criteria. Its occurrence is associated with reduced quality of life, exercise capacity and increased hospitalization rates and mortality. The clinical efficacy of treating iron deficiency has not been tested in patients with heart failure with preserved ejection fraction (HFpEF). Methods: The FAIRHFpEF trial aims to enroll patients with HFpEF, reduced exercise capacity and iron deficiency (defined as serum ferritin &lt;100 ng/mL or serum ferritin 100299 ng/mL with transferrin saturation &lt;20%). Patients will be treated in a multicenter, doubleblind, randomized clinical trial with intravenous ferric carboxymaltose (FCM) at doses aimed to replenish iron stores vs. placebo. The primary endpoint is the difference in exercise capacity from baseline to week 24 as assessed by the 6minute walk test. Secondary endpoints include healthrelated quality of life assessments such as the Kansas City Cardiomyopathy Questionnaire, the European Quality of Life5 Dimensions questionnaire and global function tests. Conclusions: The FAIRHFpEF trial is designed to investigate the effect of intravenous iron repletion in iron deficient patients with HFpEF using FCM.

Iron deficiency in heart failure with preserved ejection fraction: rationale and design of the FAIR-HFpEF trial

Background: Iron deficiency is highly prevalent in patients with heart failure and has well established diagnostic criteria. Its occurrence is associated with reduced quality of life, exercise capacity and increased hospitalization rates and mortality. The clinical efficacy of treating iron deficiency has not been tested in patients with heart failure with preserved ejection fraction (HFpEF). Methods: The FAIRHFpEF trial aims to enroll patients with HFpEF, reduced exercise capacity and iron deficiency (defined as serum ferritin &lt;100 ng/mL or serum ferritin 100299 ng/mL with transferrin saturation &lt;20%). Patients will be treated in a multicenter, doubleblind, randomized clinical trial with intravenous ferric carboxymaltose (FCM) at doses aimed to replenish iron stores vs. placebo. The primary endpoint is the difference in exercise capacity from baseline to week 24 as assessed by the 6minute walk test. Secondary endpoints include healthrelated quality of life assessments such as the Kansas City Cardiomyopathy Questionnaire, the European Quality of Life5 Dimensions questionnaire and global function tests. Conclusions: The FAIRHFpEF trial is designed to investigate the effect of intravenous iron repletion in iron deficient patients with HFpEF using FCM.

Hepcidin and Erythroferrone Levels across Human Pregnancy, and the Effect of IV Iron Infusion - a Revamp Substudy

Hepcidin is known to be suppressed in human pregnancy; and while it's known that intravenous iron infusion increases hepcidin levels, it is unknown to what degree this occurs during pregnancy. The REVAMP trial was an open label, individually randomised controlled trial, in 862 Malawian pregnant women in the second trimester, with moderate to severe anaemia (haemoglobin&amp;lt;10.0g/dL). Participants were randomised equally to either intravenous Ferric Carboxymaltose (FCM), or standard of care (Oral iron), and followed up to 28 days post partum. To evaluate hepcidin and erythroferrone levels, a total of 250 participants were randomly selected. This sample was balanced with the main trial with regards to trial arm (FCM 50%, Oral iron 50%), baseline iron deficiency (42.2%), anaemia (96.4%), parity (nulliparous 55.6%), and HIV status (HIV positive 15.3%). Hepcidin and erythroferrone levels were measured by ELISA, on serum samples collected longitudinally across 3 pregnancy timepoints (baseline, 28-days post randomisation, 36-weeks gestation), delivery, and 28-days postpartum. Serum hepcidin levels (reported as: median [IQR]) were not different between the trial arms at baseline (FCM: 11.91ng/ml [5.56-20.53], Oral iron: 12.79ng/ml [6.65-20.40]). At 28 days post randomisation, hepcidin was higher in those treated with FCM (31.92ng/ml [14.80-59.84]) than oral iron (5.85ng/ml [2.50-15.12]), p&amp;lt;0.001. Hepcidin remained significantly increased at 36 weeks gestation (FCM: 21.14ng/ml [11.84-41.62], Oral iron: 10.86ng/ml [8.34-18.03], p&amp;lt;0.001). At delivery levels were higher overall, remaining higher in those who received FCM treatment (80.56ng/ml [25.11-149.6]) than Oral iron (37.39ng/ml [16.35-91.85], p=0.001). At 28days postpartum, hepcidin remained higher in the FCM arm 39.29ng/ml [19.52-76.37] than the Oral arm 17.67ng/ml [11.05-38.21], p&amp;lt;0.001. Erythroferrone levels were not statistically different between arms at any timepoint; values were highest at baseline (FCM median 0.92ng/ml [0.42-1.45], Oral iron 1.06ng/ml [0.52-2.04]). This is the first study examining the effects of modern intravenous iron infusions on hepcidin levels during pregnancy, and demonstrates that there is a statistically significant increase in hepcidin levels after ferric carboxymaltose, throughout pregnancy, persisting to four weeks post partum.

Association between sex and efficacy of intravenous ferric carboxymaltose in patients with acute heart failure and iron deficiency: an AFFIRM-AHF subgroup analysis

Abstract Background/Introduction Heart failure (HF) pathophysiology, clinical presentation and treatment response is known to differ between males and females (1). In the AFFIRM-AHF trial, intravenous (IV) ferric carboxymaltose (FCM) reduced the risk of HF hospitalisations and improved quality of life vs placebo in patients with iron deficiency who had stabilised following an acute HF (AHF) episode (2,3); the effect of sex on outcomes with iron-repletion therapy in these high-risk patients has not been fully explored. Purpose To investigate the interaction between sex and the effects of FCM vs placebo on clinical outcomes in the AFFIRM-AHF population. Methods In AFFIRM-AHF, patients with left ventricular ejection fraction &amp;lt;50% and iron deficiency (defined as serum ferritin &amp;lt;100 ng/mL, or 100–299 ng/mL if transferrin saturation is &amp;lt;20%) who had stabilised following recent hospitalisation for AHF were randomised 1:1 to receive IV FCM or placebo for up to 24 weeks.2 The primary endpoint was a composite of total HF hospitalisations and cardiovascular (CV) death up to Week 52; secondary endpoints are listed in the Figure.2 In this prespecified analysis, AFFIRM-AHF patients were stratified into male and female subgroups and the interaction between sex and clinical outcomes with FCM vs placebo was explored. Results Of the 1108 patients included in the AFFIRM-AHF full analysis set, 614 (FCM: 314; placebo: 300) were male and 494 (FCM: 244; placebo: 250) were female. At baseline, a New York Heart Association functional class of III and above was more common in females (59.0%) than in males (48.4%). For the primary endpoint, the adjusted annualised event rate per 100 patient-years with FCM vs placebo was 53.3 vs 83.3 in males (rate ratio [RR] 0.64; 95% confidence interval [CI] 0.46–0.89) and 63.1 vs 60.3 in females (RR 1.05; 95% CI 0.72–1.53) (Figure). For all secondary endpoints except time to CV death, effect sizes in male and female subgroups were similar to those for the primary endpoint. The interaction between sex and treatment effect was non-significant for the primary endpoint (P-interaction=0.054) but reached significance for the secondary endpoints of total CV hospitalisations and CV death (P-interaction=0.024) and time to first HF hospitalisation or CV death (P-interaction=0.043). Conclusion(s) The results of this exploratory subgroup analysis suggest that iron deficiency treatment with IV FCM following an AHF episode may be more effective in males than in females; this may be related to baseline differences between sex subgroups, beyond the factors adjusted for in this analysis.Figure

The effect of iron deficiency treatment with intravenous ferric carboxymaltose on the arrhythmic burden of patients with HFrEF and cardiac implantable electronic devices

Abstract Background The deleterious effect of iron deficiency (ID) on cardiomyocyte electrochemical stability is well-documented. In patients with heart failure and reduced ejection fraction (HFrEF), ID represents a key comorbidity associated with increased morbidity and mortality. Thus, it has been hypothesized that treating ID may lead to reduced incidence of arrhythmias in HFrEF patients. Purpose To study the effect of intravenous ferric carboxymaltose (IV FCM) treatment on the iron stores, arrhythmic burden, functional capacity and quality of life in HFrEF patients with ID and cardiac implantable electronic devices (CIEDs). Methods Patients with HFrEF, ID and CIEDs scheduled to receive IV FCM as per ESC guidelines were invited to participate. Follow-up lasted 12 months. The primary outcome was related to the amelioration of patients’ iron status. Secondary outcomes relative to arrhythmic burden included (i) the incidence of device-detected ventricular tachycardias (VTs) between the year before recruitment to the study and the follow-up period, (ii) patients’ Lown and Wolf classification as derived from 24hour Holter monitoring. Data related to non-invasive arrhythmic markers such as late potential, microvolt T-wave alternans and deceleration capacity were also available. Results This real-life cohort included 79 patients (84% male). Patients’ median age was 70.8 [IRQ:11.7] years. Median ferritin increased to 150 [125] ng/mL at 12 months (baseline 55 [68] ng/mL, P&amp;lt;0.001). At their final visit, 45 (57%) patients no longer met the ESC criteria for iron deficiency (P&amp;lt;0.001). The CIED-derived incidence of VT episodes decreased significantly after 12 months of IV FCM treatment (0.26±0.83 episodes per patient per year compared to 0.8±2.36, P = 0.048). Patients were also significantly likely to shift to a more favorable Lown and Wolf arrhythmic burden classification (P = 0.01). Patients’ late potential results and microvolt T-wave alternans also improved significantly (P = 0.01 for both tests). Conclusion The results of this real-life cohort analysis suggest significant reduction of the arrhythmic burden in HFrEF and ID after restitution of iron stores. Further studies are needed to further evaluate the impact of these results.

Efficacy and safety of intravenous iron repletion in patients with heart failure: a systematic review and meta-analysis

Abstract Introduction AFFIRM-AHF and IRONMAN demonstrated lower rates of the combined endpoint recurrent heart failure (HF) hospitalizations and cardiovascular death (CVD) by using intravenous (IV) ferric carboxymaltose (FCM) and ferric derisomaltose (FDI), respectively in patients with HF and iron deficiency (ID) utilizing prespecified COVID-19 analyses. Material and methods We meta-analyzed efficacy, between trial heterogeneity and data robustness for the primary endpoint and CVD in AFFIRM-AHF and IRONMAN. As sensitivity analysis, we analyzed data from all eligible exploratory trials investigating FCM/FDI in HF. Results FCM/FDI reduced the primary endpoint (RR = 0.81, 95% CI 0.69-0.95, p = 0.01, I2 = 0%), with the number needed to treat (NNT) being 7. Power was 73% and findings were robust with fragility index (FI) of 94 and fragility quotient (FQ) of 0.041. Effects of FCM/FDI were neutral concerning CVD (OR = 0.88, 95% CI 0.71-1.09, p = 0.24, I2 = 0%). Power was 21% while findings were fragile with reverse FI of 14 and reversed FQ of 0.006. The sensitivity analysis from all eligible trials (n = 3,258) confirmed positive effects of FCM/FDI on the primary endpoint (RR = 0.77, 95% CI 0.66-0.90, p = 0.0008, I2 = 0%), with NNT being 6. Power was 91% while findings were robust (FI of 147 and FQ of 0.045). Effect on CVD was neutral (RR = 0.87, 95% CI 0.71-1.07, p = 0.18, I2 = 0%). Power was 10% while findings were fragile (reverse FI of 7 and reverse FQ of 0.002). Rate of infections (OR = 0.85, 95% CI 0.71-1.02, p = 0.09, I2 = 0%), vascular disorder (OR = 0.84, 95% CI 0.57-1.25, p = 0.34, I2 = 0%) and general or injection-site related disorders (OR = 1.39, 95% CI 0.88-1.29, p = 0.16, I2 = 30%) were comparable between groups. There was no relevant heterogeneity (I2&amp;gt;50%) between the trials for any of the analyzed outcomes. Conclusions Use of FCM/FDI is safe and reduces the composite of recurrent HF hospitalizations and CVD without benefit on CVD. Findings concerning composite outcomes exhibit a high level of robustness without heterogeneity between trials with FCM and FDI.Summary

Incidence of postpartum depression after treatment of postpartum anaemia with intravenous ferric carboxymaltose, intravenous ferric derisomaltose or oral ferrous sulphate: A randomized clinical trial

ObjectivesThis study aimed to explore whether the type of iron preparation used to treat postpartum anaemia affects the incidence of postpartum depression and whether the risk of postpartum depression is higher in postpartum patients with anaemia who were adequately treated compared to the general postpartum population. Study designSingle-center, open-label, randomized trial. Women were allocated to receive intravenous ferric carboxymaltose, intravenous ferric derisomaltose or oral ferrous sulphate. Intravenous iron was given in one or two doses, while ferrous sulphate as two 80 mg tablets once daily. Primary outcome was postpartum depression measured by Edinburgh Postnatal Depression Scale (EPDS) six weeks postpartum. Haematological parameters were analyzed as secondary outcomes. Kruskal-Wallis test was used for group comparison (p < 0.05 significant). The chi-square test was applied to compare categorical variables as well as the group of all subjects treated for anaemia in the study with the historical data for the Slovenian postpartum population. ResultsThree-hundred women with postpartum anemia (hemoglobin < 100 g/L within 48-hours postpartum) were included between September 2020 and March 2022 in tertiary perinatal center. Most characteristics were similar across groups. EPDS score at six weeks postpartum did not differ between groups. The treatment modality of postpartum anaemia did not have a statistically significant effect on the EPDS score six weeks after treatment (p = 0.10), nor did it have a statistically significant effect on the difference in EPDS scores before and after treatment (p = 0.68). The proportions of participants who scored 10 or more points on the EPDS scores at six weeks postpartum were not statistically different between the groups (p = 0.79). The proportion of participants with an EPDS score of 10 or more at six weeks postpartum in the total study population did not differ significantly from previously reported proportion of postpartum women with EPDS score of 10 or more in the general population (12 % vs. 21 %; p < 0.001). ConclusionsMaternal depression at 6 weeks postpartum did not differ in women treated for postpartum anemia with intravenous ferric carboxymaltose, intravenous ferric derisomaltose or oral ferrous sulphate. Participants with postpartum anaemia who are adequately treated with either oral or intravenous iron preparations are not at a higher risk of postpartum depression than the general population at six weeks postpartum.

Efficacy and Safety of Intravenous Ferric Carboxymaltose Treatment of Iron Deficiency Anaemia in Patients with Corpus Atrophic Gastritis: A Retrospective Study.

Corpus Atrophic Gastritis (CAG) is characterised by iron malabsorption leading to iron deficiency anaemia (IDA), which rarely responds to oral therapy. Ferric carboxymaltose (FCM), shown to be a safe and effective intravenous iron therapy in other diseases, has not been investigated yet in CAG. Thus, we aimed to assess the safety and efficacy of FCM in CAG-related IDA. A retrospective study on 91 patients identified CAG as the only cause of IDA treated with FCM. Twenty-three were excluded for incomplete follow-up. Sixty-eight were evaluated for safety and efficacy, while three were evaluated for safety only due to infusion interruption for side effects. Haemoglobin and iron storage were evaluated pre-infusion (T0), at 4 weeks (T4) and 12 weeks (T12) after infusion. An eventual IDA relapse was analysed. Two cases reported mild side effects. Haemoglobin significantly increased at T4, and T12, reaching +3.1 g/dL. Ferritin increased at T4, decreasing at T12, while transferrin saturation increased progressively until reaching a plateau. IDA relapsed in 55.4% of patients at a mean of 24.6 months. The only factor associated with relapse was female gender [OR (95% CI): 6.6 (1.5-28.6)]. FCM proved to be safe and effective in treating CAG-related IDA, ensuring quick and long-lasting recovery.

Intravenous ferric carboxymaltose and ferric derisomaltose alter the intestinal microbiome in female iron-deficient anemic mice.

Iron deficiency anemia (IDA) is a leading global health concern affecting approximately 30% of the population. Treatment for IDA consists of replenishment of iron stores, either by oral or intravenous (IV) supplementation. There is a complex bidirectional interplay between the gut microbiota, the host's iron status, and dietary iron availability. Dietary iron deficiency and supplementation can influence the gut microbiome; however, the effect of IV iron on the gut microbiome is unknown. We studied how commonly used IV iron preparations, ferric carboxymaltose (FCM) and ferric derisomaltose (FDI), affected the gut microbiome in female iron-deficient anemic mice. At the phylum level, vehicle-treated mice showed an expansion in Verrucomicrobia, mostly because of the increased abundance of Akkermansia muciniphila, along with contraction in Firmicutes, resulting in a lower Firmicutes/Bacteroidetes ratio (indicator of dysbiosis). Treatment with either FCM or FDI restored the microbiome such that Firmicutes and Bacteroidetes were the dominant phyla. Interestingly, the phyla Proteobacteria and several members of Bacteroidetes (e.g., Alistipes) were expanded in mice treated with FCM compared with those treated with FDI. In contrast, several Clostridia class members were expanded in mice treated with FDI compared with FCM (e.g., Dorea spp., Eubacterium). Our data demonstrate that IV iron increases gut microbiome diversity independently of the iron preparation used; however, differences exist between FCM and FDI treatments. In conclusion, replenishing iron stores with IV iron preparations in clinical conditions, such as inflammatory bowel disease or chronic kidney disease, could affect gut microbiome composition and consequently contribute to an altered disease outcome.