Intravenous Iron Supplementation Research Articles

A randomized double-blind pilot study to evaluate the efficacy, safety, and tolerability of intravenous iron versus oral iron for the treatment of restless legs syndrome in patients with iron deficiency anemia.

Restless legs syndrome (RLS) is a neurological disorder that can have a profound effect on sleep and quality of life. Idiopathic RLS is associated with brain iron insufficiency despite normal peripheral iron stores. There is, however, a five- to six-fold increase in prevalence of RLS in patients with iron deficiency anemia (IDA). Several open-label trials have demonstrated symptomatic improvement in RLS following treatment of IDA using oral or intravenous iron supplementation. To date, there have been no randomized double-blind controlled trials of intravenous iron compared with oral iron for the treatment of RLS patients with IDA. In the current study, oral ferrous sulfate and ferumoxytol were compared for efficacy and speed of response for treatment of RLS occurring in patients with IDA. The planned recruitment for this study was 70 patients with RLS and IDA, to be randomly assigned 1:1 to oral or intravenous iron, using double-blind, double-dummy procedures. At Week 6, the primary outcomes of Clinical Global Impression-Improvement score and change from baseline in the International Restless Legs Syndrome Study Group rating scale score were assessed. Due to challenges, performing the clinical trial during the COVID-19 pandemic, final-week data were found missing for 30 patients. As a result, in order to maintain the prespecified statistical analysis, an additional 30 patients were recruited. Both IV and oral iron were associated with a marked improvement in RLS symptoms, with no statistically significant difference between treatment groups. No serious adverse events were observed in either treatment group.

Jehovah’s Witness Needing Critical Care: A Narrative Review on the Expanding Arsenal

Present day Jehovah’s Witness (JW) religion accounts for 8.5 million followers. A tenant feature of the JW faith is religious objection to transfusions of blood and blood products. Interpatient variability, as it pertains to blood and blood products may occur; hence, a confidential interview will determine which products individual may consent to (Marsh and Bevan, 2002). This belief and practice place great restrictions on treating medical professionals in scenarios of life-threatening anaemia and active haemorrhage. The review to follow explores the physiological and pathophysiological consequences of severe anaemia. Non-blood transfusion practices are explored, many of which are potentially lifesaving. Particular attention is drawn to the evolving science involving artificial oxygen carriers and their use in emergency situations. A greater safety profile ensures its future use amongst religious objectors to be greatly beneficial. Intravenous iron supplementation has enjoyed a lively debate within the critical care community. A review of recent systematic and meta-analysis supports its use in the ICU; however, more investigation is needed into the complementary use of hepcidin.

Imbalance of Iron Availability and Demand in Patients With Acute and Chronic HeartFailure.

Iron deficiency (ID) is a frequent comorbidity in patients with acute (AHF) and chronic heart failure (CHF) associated with morbidity and death. We aimed to better characterize iron homeostasis in patients with heart failure applying different biomarkers and to evaluate the accuracy of current ID definition by the European Society of Cardiology/American College of Cardiology/American Heart Association to indicate tissue iron availability and demand. We performed a retrospective cohort study investigating 277 patients with AHF and 476 patients with CHF between February 2021 and May 2022. Patients with AHF had more advanced ID than patients with CHF, reflected by increased soluble transferrin receptor and soluble transferrin receptor-ferritin index, and lower ferritin, serum iron, transferrin saturation, hepcidin, and reticulocyte hemoglobin. Decreased iron availability or increased tissue iron demand, reflected by increased soluble transferrin receptor-ferritin index and decreased reticulocyte hemoglobin, was found in 84.1% (AHF) and 28.0% (CHF) with absolute ID and in 50.0% (AHF) and 10.5% (CHF) with combined ID according to the current European Society of Cardiology/American College of Cardiology/American Heart Association-based ID definition. Low hepcidin expression as an indicator of systemic ID was found in 91.1% (AHF) and 80.4% (CHF) of patients with absolute ID and in 32.3% (AHF) and 18.8% (CHF) of patients with combined ID. ID definitions with higher specificity reduce the need for iron supplementation by 25.5% in patients with AHF and by 65.6% in patients with CHF. Our results suggest that the current European Society of Cardiology/American College of Cardiology/American Heart Association-based ID definition might overestimate true ID, particularly in CHF. More stringent thresholds for ID could more accurately identify patients with heart failure with reduced tissue iron availability who benefit from intravenous iron supplementation.

Correction of hyperphosphatemia in a patient with end-stage chronic kidney disease and a complex case of anemia. A clinical case

Iron supplements and/or blood transfusions in combination with recombinant human erythropoietin injections are routinely used to correct renal anemia, which is a common complication of end-stage renal disease. However, massive blood transfusions and inadequate intravenous iron supplementation can lead to iron overload syndrome, and anemia is not always nephrogenic. A rare clinical case of a patient with end-stage chronic kidney disease with complex genesis of anemia, who is on hemodialysis, is presented. The case is interesting because the prescription of first-line drugs was life-threatening in nature, and sevelamer was the drug chosen for the correction of mineral-bone disorders.

Intravenous Iron Supplementation in Pregnancy: A Quality Improvement Project on Maternal Transfusion Reduction [ID 2683469

INTRODUCTION: Intravenous (IV) iron supplementation for patients with iron deficiency anemia in pregnancy has been shown to improve hemoglobin (Hb) levels in the peripartum period and ultimately lead to a decrease in severe maternal morbidity (SMM), specifically blood transfusion. The objective of this study was to analyze the effects of IV iron supplementation on maternal pre-delivery Hb levels after the implementation of an institution-based protocol focused on maternal red blood cell transfusion reduction. METHODS: We performed a retrospective review of patients who received IVFe supplementation after the implementation of a maternal transfusion reduction bundle at our Level IV maternal care center in 2020. We reviewed changes in maternal Hb pre-infusion and pre-delivery over a 3-year period (2020–2023), along with rates of postpartum blood transfusion. Patients were excluded if they received an antepartum blood transfusion. Maternal demographics, ferritin and Hg levels were compared between the two groups using GraphPad Prism software. RESULTS: Two hundred ninety-five patients met inclusion criteria; most patients were Hispanic (71.9%), had Medicaid (51.9%), and underwent a vaginal delivery (76.9%). Mean gestational age at time of infusion was 34.2 weeks (95% CI, 33.7–34.7) The average Hb pre-infusion and pre-delivery were 8.9 (95% CI, 8.8–9.0) and 10.6 (95% CI, 10.4–10.8), respectively. The change in maternal Hb at time of delivery increased by 2 points (P<.0001). Only two patients received a blood transfusion postpartum. CONCLUSION: Implementation of a standardized antenatal IV iron infusion protocol can improve maternal pre-delivery Hb levels and reduce morbidity associated with blood transfusion.

Intravenous Iron Supplementation Timing in Pregnancy: A Quality Improvement Project on Maternal Transfusion Reduction [ID 2683470

INTRODUCTION: Intravenous iron supplementation (IVFe) for pregnant patients with iron deficiency anemia improves hemoglobin (Hb) levels in the peripartum period. Optimal timing of this therapy, however, is unknown. We analyzed the effects of IVFe as part of an institution-based protocol on maternal Hb levels, stratifying by gestational age (GA). METHODS: We reviewed changes in maternal Hb pre-infusion and pre-delivery over a 3-year period (2020–2023) after the implementation of a maternal transfusion reduction bundle was incorporated at our Level IV maternal care center in 2020. Pregnant patients who received IVFe and delivered at our institution were included and compared by gestational age (<34 or ≥34 weeks) at time of IVFe. We excluded patients with known antepartum blood transfusion. Maternal demographics, ferritin and Hg levels were compared between the two groups using GraphPad Prism software. RESULTS: Of 295 patients who met inclusion criteria, maternal age, body mass index, nulliparity, and ferritin levels were similar in both groups. Mean GA for the cohorts at time of IV iron transfusion were 29.6 ± 4.9 weeks (early third trimester) and 36.6 ± 2.4 weeks (late third trimester), respectively (P<.0001). Higher delta Hb (2.5 g/dL at <34 weeks versus 1.3 g/dL at ≥34 weeks) and improved mean pre-delivery Hb were seen when IV iron was given in the early third trimester (P<.0001). CONCLUSION: Early third-trimester IVFe improves maternal pre-delivery Hb levels and may reduce significant maternal morbidity hemorrhage complications.

Intravenous Iron Supplementation in Pregnancy: Comparisons of Dosage and Latency of Infusion Based on a Quality Improvement Project on Maternal Transfusion Reduction [ID 2683380

INTRODUCTION: Optimal dosing of intravenous iron supplementation (IVFe) and latency of the infusion for pregnant patients with iron deficiency anemia has been minimally evaluated. We analyzed the effects of specific IVFe dosage parameters as part of an institution-based protocol on maternal peripartum hemoglobin (Hb) levels stratifying by time of infusion to delivery. METHODS: We reviewed average changes in maternal Hb pre-infusion and pre-delivery over a 3-year period (2020–2023) after the implementation of a maternal transfusion reduction bundle was incorporated at our Level IV maternal care center in 2020. Pregnant patients who received IVFe and delivered at our institution were included and compared by IVFe dosage forms (800 mg) and infusion latency (by 2-week increments). We excluded patients with known antepartum blood transfusion. Maternal demographics and all comparison groups were analyzed among each other using GraphPad Prism software. RESULTS: Two hundred ninety-five patients met inclusion criteria. Demographics of maternal age, body mass index (BMI), nulliparity, and ferritin levels were similar in all groups. We found a statistically significant difference in improved pre-delivery Hb with larger IVFe doses (P=.002) and longer infusion-delivery periods (P=.049). A Tukey post-hoc test revealed that the highest yield on mean delta Hb was after 6–8 weeks or longer of latency with doses greater than 800 mg versus less than 2 weeks at doses of 800 mg or lower (2.6–3.1 g/dL; P<.0001). CONCLUSION: Latency periods of at least 6 weeks with IVFe dosages of 800 mg or greater, regardless of maternal BMI or starting ferritin, may markedly improve pre-delivery Hb levels and ultimately reduce maternal morbidity hemorrhage complications.

Comparison of Oral Versus Intravenous Iron Therapy in Improving Hemoglobin Status in Patients of Chronic Kidney Disease

Anemia (particularly iron deficiency) is an important concern in patients with chronic kidney disease (CKD) as it reflects the outcome of the disease. Objective: To compare the treatment efficacy of oral versus intravenous iron supplementation in improving the hemoglobin status of patients with chronic kidney disease not on hemodialysis or erythropoietin. Methods: Randomized controlled trial was carried out in Medicine Department of Pak Emirates Military Hospital, Rawalpindi from Jun 2023 to Dec 2023. Patients in Group I received intravenous iron sucrose 200 mg once a week diluted in 500 ml of 0.9% normal saline given over 60-90 minutes. Patients in Group O received oral iron supplementation in a dose of 325 mg (containing 65 mg of elemental iron) thrice a day taken one hour before taking their meals with a glass of water. The treatment was continued for 4 weeks. Results: Mean values of serum iron were 84.41±5.56 mcg/dl in Group I versus 84.67±5.43 mcg/dl in Group O before the start of therapy (p=0.726). Serum values for iron post-therapy were 143.40±6.01 mcg/dl in Group I versus 125.35±6.68 mcg/dl in Group O (p<0.001). Mean values for serum hemoglobin were 7.74±0.74 g/dl in Group I versus 7.61±0.82 g/dl in Group O before the start of therapy (p=0.256). Serum values of Hb post-therapy were 12.31±0.71 g/dl in Group I versus 9.91±0.82 g/dl in Group O (p<0.001). Conclusions: We conclude that Intravenous (IV) iron is superior to oral iron supplementation in improving iron stores and Hb levels in CKD patients not on dialysis and/or erythropoietin

Utilisation of intravenous iron and erythropoietin in dialysis patients: A prospective observational study

In this prospective observational study, the utilization of intravenous iron and erythropoietin in dialysis patients was thoroughly investigated. The study aimed to assess the effectiveness of these treatments in managing anaemia, a common complication in individuals undergoing dialysis. Anaemia is a significant concern in this population due to impaired erythropoiesis and iron deficiency resulting from renal dysfunction. The study followed a cohort of dialysis patients, tracking their response to intravenous iron supplementation and erythropoietin therapy over a specified period. Through regular monitoring and evaluation, the study sought to determine the impact of these interventions on haemoglobin levels, transfusion requirements, and overall patient outcomes. Additionally, the study likely analysed factors such as dosing regimens, adverse effects, and the need for additional interventions to achieve optimal haemoglobin levels. By conducting a prospective observational study, researchers aimed to provide valuable insights into the real-world effectiveness and safety of intravenous iron and erythropoietin in managing anaemia in dialysis patients, which could inform clinical practice and improve patient care strategies.

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.

Iron supplementation in patients with chronic inflammatory bowel disease: recommendations for a practical approach

Iron deficiency is the predominant cause of anemia. Iron deficiency anemia plays a major role, especially in patients with inflammatory bowel disease (IBD), and is the most common extraintestinal manifestation and IBD-associated systemic complication. The presence of anemia leads to a reduction in quality of life in patients with IBD associated with limitations in physical, emotional, and cognitive function. In addition, it is associated with an increased hospitalization rate. For this reason, iron supplementation is of particular importance. Oral and intravenous iron supplements are used to treat iron deficiency. Due to the lack of absorption and gastrointestinal side effects of oral substitution, intravenous supplementation is becoming increasingly important. However, there are still certain concerns about intravenous administration.With the help of this review, we want to address the topic of iron substitution in patients with IBD, summarize current guideline recommendations, and provide a practical approach.

Chemotherapy-Induced Anemia in Adults Incidence and Treatment

Chemotherapy-induced anemia is the predominant adverse event observed in individuals undergoing cancer treatment, resulting in a reduction in red blood cells and hemoglobin levels. This condition manifests through indicators such as diminished quality of life and fatigue. Effective approaches for managing recurrent chemotherapy-induced anemia encompass the use of erythropoietin-stimulating agents, blood transfusions, and intravenous iron supplementation. Each of these interventions presents distinct pros and cons, with selecting a particular treatment modality contingent upon the severity of anemia and the duration of malignancy. A comprehensive review of scholarly literature reveals a high prevalence of anemia among cancer patients receiving chemotherapy. Ongoing research endeavors are focused on developing pharmacological agents for cancer treatment that are devoid of adverse effects, particularly concerning anemia, a common complication associated with this therapeutic approach.

Strategies for Managing Anemia in Chronic Kidney Disease

Anemia is a common complication in chronic kidney disease (CKD) and is associated with decreased quality of life, deteriorating kidney function, increased illness, higher mortality rates, and elevated healthcare costs. Management of CKD-related anemia aims to enhance renal function (when feasible) and bolster red blood cell production. Anemia in chronic kidney disease (CKD) stems from a variety of factors, including reduced erythropoietin (EPO) production, inadequate iron availability or functionality, and inflammation leading to heightened levels of hepcidin, among other causes. Typical treatment for CKD-related anemia involves administering oral or intravenous iron supplements in conjunction with erythropoiesis-stimulating agents (ESAs). Over the past decade, erythropoiesis-stimulating agents (ESAs) have proven effective in boosting hemoglobin (Hb) levels for many patients. However, concerns about their safety, particularly regarding increased cardiovascular risk—especially at high doses and in hyporesponsive patients—have emerged. As a result, there's been a shift towards adopting more cautious Hb targets. Iron deficiency is widespread among CKD patients, particularly in those not undergoing dialysis. While iron supplementation has traditionally been used to support anemia management, there's growing recognition of the potential benefits of intravenous iron therapy, especially in the context of heart failure. HIF prolyl hydroxylase inhibitors are promising new drugs being clinically evaluated as alternatives to ESAs for anemia treatment in CKD patients. Initial data suggest they effectively boost endogenous erythropoietin production with potential benefits like lower peak concentrations, efficacy in inflamed patients, and improved iron utilization. However, further research is needed to confirm their safety and efficacy in the long term use.
 Keywords: anemia, chronic kidney disease, erythropoiesis-stimulating agents, iron, HIF-prolyl-hydroxylase inhibitors

Compliance With NCCN Guidelines for Evaluation and Treatment of Anemia Among Patients With Solid Tumors.

NCCN Guidelines for Hematopoietic Growth Factors recommend evaluation and treatment of anemia in patients with cancer. However, a paucity of data exists regarding compliance with these recommendations. A retrospective cohort study was performed of patients diagnosed with any solid tumor at Vanderbilt University Medical Center from 2008 to 2017. Tumor registry-confirmed cancer cases were identified by ICD-O codes using the Synthetic Derivative database. Anemia was defined as hemoglobin (Hgb) level ≤11 g/dL and graded according to CTCAE version 5.0. Absolute, functional, and possible functional iron deficiency were defined based on NCCN Guidelines. A total of 25,018 patients met inclusion criteria. Median age was 60 years. The most common malignancies were respiratory tract, prostate, and nonprostate urologic (11% each). Among 8,695 patients with Hgb levels available prior to diagnosis, 1,484 (17%) were noted to be anemic proximal to diagnosis. Of the 25,018 patients, 11,019 (44%) were anemic within 6 months of diagnosis. Of these patients, 4,686 (43%) had grade 2 (moderate) anemia and 9,623 (87%) had normocytic anemia. Patients with retroperitoneal/peritoneal cancers had the highest prevalence of anemia (83/110; 75%). A total of 4,125 (37%) underwent any evaluation of their anemia, of whom 1,742 (16%) had iron studies performed and 1,528 (14%) had vitamin B12 or folate studies performed. Fewer than half of patients with anemia received treatment (n=4,318; 39%), including blood transfusion (n=3,528; 32%), oral iron supplementation (n=1,279; 12%), or intravenous iron supplementation (n=97; 1%). Anemia treatment was significantly more frequent as the grade of anemia increased (any treatment among grade 1/mild: 12%; grade 2/moderate: 31%; grade 3/severe: 77%; χ2 [2, n=11,019]=3,020.6; P<.001). Patients with penile and testicular cancers had the highest prevalence of anemia evaluation (n=57; 79%). Anemia is common in patients with solid tumors; yet, compliance with NCCN Guidelines for evaluation and treatment of anemia remains low. There are opportunities to improve compliance with guidelines across the spectrum of cancer care.

Iron deficiency in pernicious anemia: Specific features of iron deficient patients and preliminary data on response to iron supplementation

While vitamin B12 (B12) deficiency is considered as the hallmark of pernicious anemia (PA), iron deficiency (ID) is also prevalent. Indeed, this auto immune gastritis is responsible for parietal cell atrophy and increase in gastric pH, leading to impaired iron absorption. We compared PA patients' features according to their iron status at PA diagnosis, and we assessed the iron status recovery after oral or intravenous iron supplementation. We prospectively included patients presenting with a newly diagnosed PA in a tertiary referral hospital between November 2018 and October 2020. Iron status was assessed at PA diagnosis then regularly during a standardized follow-up. In case of ID, the decision of treatment with oral and/or intravenous iron supplementation was left to the clinician convenience. We included 28 patients with newly diagnosed PA. ID was observed in 21/28 (75.0%) patients: from the PA diagnosis in 13 patients, or during the follow-up in 8 patients. Iron deficient PA patients had higher plasma B12 (p=0.04) and lower homocysteine levels (p=0.04). Also, ID was independently associated with the 'APCA (anti-parietal cell antibodies) alone' immunological status (absence of anti-intrinsic factor antibodies) after adjustment for age, gender and B12 level (aOR 12.1 [1.1-141.8], p=0.04). High level of APCA was associated with lower ferritin level. After 3 months of supplementation, 3/11PA patients normalized the iron status with oral iron supplementation, versus 7/8 with intravenous iron supplementation (p=0.02). The high frequency of iron deficiency in PA highlights the interest of regular assessment of iron status in this condition. ID was associated with a profile including APCA alone and less pronounced B12 deficiency. Intravenous iron supplementation seemed to be more efficient than an oral supplementation in these preliminary data.

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.

Evaluation of the efficacy and safety of intravenous infusion of ferric derisomaltose in the treatment of iron deficiency anemia: a single-center retrospective analysis

Objective: To investigate the clinical efficacy and safety of ferric derisomaltose injection versus iron sucrose injection in the treatment of iron deficiency anemia (IDA) . Methods: A total of 120 patients with iron deficiency anemia admitted from June 2021 to March 2023 were given intravenous iron supplementation with ferric derisomaltose to assess the efficacy and safety of hemoglobin (HGB) elevation before and after treatment. Simultaneously, the clinical effects of iron supplementation with iron sucrose were compared to those of inpatient patients during the same period. Results: Baseline values were comparable in both groups. Within 12 weeks of treatment, the elevated HGB level in the ferric derisomaltose group was higher than that of the iron sucrose group, with a statistical difference at all time points, and the proportion of HGB increased over 20 g/L in the patients treated for 4 weeks was higher (98.7%, 75.9% ). During the treatment with ferric derisomaltose and iron sucrose, the proportion of mild adverse reactions in the ferric derisomaltose group was slightly lower than that of the iron sucrose group, and neither group experienced any serious adverse reactions. The patients responded well to the infusion treatment, with no reports of pain or pigmentation at the injection site. Conclusion: The treatment of IDA patients with ferric derisomaltose has a satisfactory curative effect, with the advantages of rapidity, accuracy, and safety. Therefore, it is worthy of widespread clinical use.

Latest pharmaceutical approaches across the spectrum of heart failure.

Despite major advances in prevention and medical therapy, heart failure (HF) remains associatedwith high morbidity and mortality, especially in older and frailer patients. Therefore, acomplete, guideline-based treatment is essential, even in HF patients with conditionstraditionally associated with a problematic initiation and escalation of the medical HFtherapy, such as chronic kidney disease and arterial hypotension, as the potential adverse effects areovercome by the overall decrease of the absolute risk. Furthermore, since the latestdata suggest that the benefit of a combined medical therapy (MRA, ARNI, SGLT2i,beta-blocker) may extend up to a LVEF of 65%, further trials on these subgroups ofpatients (HFmrEF, HFpEF) are needed to re-evaluate the guideline-directed medicaltherapy across the HF spectrum. In particular, the use of SGLT2i was recentlyextended to HFpEF patients, as evidenced by the DELIVER and EMPEROR-preservedtrials. Moreover, the indication for other conservative treatments in HF patients, suchas the intravenous iron supplementation, was accordingly strengthened in the latestguidelines. Finally, the possible implementation of newer substances, such as finerenone, in guideline-directed medical practice for HF is anticipated with great interest.

Increasing rates of screening and treatment of iron deficiency in ambulatory patients with heart failure with reduced ejection fraction: a quality improvement cohort study

IntroductionIron deficiency anaemia (IDA) is common in patients with heart failure (HF) and is associated with advanced HF and increased mortality. Intravenous iron supplementation increases exercise tolerance, improves quality of...

A novel scenario in the therapeutic management of anemia of chronic kidney disease: placement and use of roxadustat.

Anemia is a frequent and early chronic kidney disease (CKD) complication. Its management is currently based on oral or intravenous iron supplements, erythropoiesis-stimulating agents, and red blood cell transfusions, when the benefits of transfusion outweigh the risks. Anemia in CKD patients is underdiagnosed and undertreated. Current standard of care is associated with challenges and therefore new treatment approacheshave been sought. Hypoxia-inducible factor-prolyl-hydroxylase enzyme inhibitors are a new class of orally administered drugs used to treat anemia associated with CKD. Small-molecule hypoxia-inducible factor-prolyl-hydroxylase inhibitors have a novel mechanism of action that activates the hypoxia-inducible factor (oxygen-sensing) pathway resulting in a coordinated erythropoietic response, leading to increased endogenous erythropoietin production, improved iron absorption and transport, and reduced hepcidin. Roxadustat is the first hypoxia-inducible factor-prolyl-hydroxylase inhibitor approved by the European Medicines Agency (EMA) and reimbursed in Italy by the Italian Medicines Agency (AIFA) for the treatment of adult patients with symptomatic CKD-related anemia. This authorization was based on the outcome of a globally-conducted phase 3 clinical trial program comprising eight pivotal multicenter randomized studies. In the absence of up-to-date guidelines, we performed a critical appraisal of the placement and use of roxadustat in this therapeutic context.