ferric-carboxymaltose and Deficiency-Diseases

Therapy with i.v. iron in patients with chronic heart failure (CHF) and iron deficiency (ID) improves symptoms, functional capacity, and quality of life. We sought to investigate whether these beneficial outcomes are independent of anaemia.. FAIR-HF randomized 459 patients with CHF [NYHA class II or III, LVEF ≤40% (NYHA II) or ≤45% (NYHA III)] and ID to i.v. iron as ferric carboxymaltose (FCM) or placebo in a 2:1 ratio. We analysed the efficacy and safety according to the presence or absence of anaemia (haemoglobin ≤120 g/L) at baseline. Of 459 patients, 232 had anaemia at baseline (51%). The effect of FCM on the primary endpoints of self-reported Patient Global Assessment (PGA) and NYHA class at week 24 was similar in patients with and without anaemia [odds ratio (OR) for improvement, 2.48 vs. 2.60, P = 0.97 for PGA and 1.90 vs. 3.39, P = 0.51 for NYHA). Results were also similar for the secondary endpoints, including PGA and NYHA at weeks 4 and 12, 6 min walk test distance, Kansas City Cardiomyopathy Questionnaire overall score, and European Quality of Life-5 Dimensions Visual Analogue Scale at most time points. Regarding safety, no differences were noticed in the rates of death or first hospitalization between FCM and placebo both in anaemic and in non-anaemic patients.. Treatment of ID with FCM in patients with CHF is equally efficacious and shows a similar favourable safety profile irrespective of anaemia. Iron status should be assessed in symptomatic CHF patients both with and without anaemia and treatment of ID should be considered.

Topics: Administration, Intravenous; Aged; Anemia, Iron-Deficiency; Case-Control Studies; Chronic Disease; Deficiency Diseases; Female; Ferric Compounds; Heart Failure; Hematinics; Humans; Iron Deficiencies; Male; Maltose; Middle Aged; Quality of Life; Treatment Outcome

About 2-3 % of the population participates in blood donation programmes. Each whole blood donation or ten apheresis donations cause a loss of 200-250 mg of iron. As a result, one of the most common risks of regular blood donors is iron deficiency. Although this has been known for decades, in most countries, iron status is currently not assessed or treated in this population. Premenopausal women are particularly affected, as they have lower iron reserves and higher daily requirements. Besides anaemia, iron deficiency may lead to fatigue and impaired cognitive and physical performance. Current iron preparations for intravenous administration are well tolerated and allow for application of large doses up to 1 g in one visit. Our hypothesis is that in blood donors with iron deficiency, intravenously administered iron is more efficient and as safe as oral iron supplementation. Since anaemia is one of the most frequent reasons for permanent or intermittent donor deferral, maintaining an iron-replete donor pool may help to prevent shortages in blood supply and to avoid iron deficiency-related comorbidities.. In this randomised clinical trial we include male and female blood donors aged ≥18 and ≤65 years with a ferritin value of ≤30 ng/ml. Stratified by gender, participants are randomized with a web-based randomisation tool in a 1:1 ratio to either 1 g of intravenously administered ferric carboxymaltose or 10 g of iron fumarate supplements at one to two daily doses of 100 mg each. Eight to 12 weeks after the first visit, iron status, blood count and symptoms are assessed in both groups. The primary endpoint is the difference in transferrin saturation (%) following the intervention between both groups. Secondary endpoints include other parameters of iron metabolism and red blood cell count, the number of patients with drug-related adverse events, and subjective symptoms including those of the restless legs syndrome, quality of life, and fatigue.. Iron supplementation administered intravenously in non-anaemic but iron-deficient blood donors could represent an effective strategy to protect blood donors from comorbidities related with iron deficiency and therefore improve blood donor wellbeing. Furthermore, iron supplementation will help to maintain an iron-replete blood donor pool.. EudraCT: 2013-000327-14, Clinical Trials Identifier: NCT01787526 . Registered on 6 February 2013.

Topics: Administration, Oral; Adolescent; Adult; Aged; Biomarkers; Blood Donors; Clinical Protocols; Deficiency Diseases; Erythrocyte Count; Female; Ferric Compounds; Ferrous Compounds; Hematinics; Humans; Infusions, Intravenous; Iron; Iron Deficiencies; Male; Maltose; Middle Aged; Prospective Studies; Research Design; Time Factors; Transferrin; Treatment Outcome; Young Adult

Iron deficiency without anemia is prevalent in patients with idiopathic pulmonary arterial hypertension and associated with reduced exercise capacity and survival.. We hypothesized that iron deficiency is involved in the pathogenesis of pulmonary hypertension and iron replacement is a possible therapeutic strategy.. Rats were fed an iron-deficient diet (IDD, 7 mg/kg) and investigated for 4 weeks. Iron deficiency was evident from depleted iron stores (decreased liver, serum iron, and ferritin), reduced erythropoiesis, and significantly decreased transferrin saturation and lung iron stores after 2 weeks IDD. IDD rats exhibited profound pulmonary vascular remodeling with prominent muscularization, medial hypertrophy, and perivascular inflammatory cell infiltration, associated with raised pulmonary artery pressure and right ventricular hypertrophy. IDD rat lungs demonstrated increased expression of hypoxia-induced factor-1α and hypoxia-induced factor-2α, nuclear factor of activated T cells and survivin, and signal transducers and activators of transcription-3 activation, which promote vascular cell proliferation and resistance to apoptosis. Biochemical examination showed reduced mitochondrial complex I activity and mitochondrial membrane hyperpolarization in mitochondria from IDD rat pulmonary arteries. Along with upregulation of the glucose transporter, glucose transporter 1, and glycolytic genes, hk1 and pdk1, lung fluorine-18-labeled 2-fluoro-2-deoxyglucose ligand uptake was significantly increased in IDD rats. The hemodynamic and pulmonary vascular remodeling were reversed by iron replacement (ferric carboxymaltose, 75 mg/kg) and attenuated in the presence of iron deficiency by dichloroacetate and imatinib, 2 putative treatments explored for pulmonary arterial hypertension that target aerobic glycolysis and proliferation, respectively.. These data suggest a major role for iron in pulmonary vascular homeostasis and support the clinical evaluation of iron replacement in patients with pulmonary hypertension.

Topics: Animals; Antihypertensive Agents; Arterial Pressure; Benzamides; Cell Proliferation; Deficiency Diseases; Dichloroacetic Acid; Disease Models, Animal; Erythropoiesis; Ferric Compounds; Ferritins; Glycolysis; Hematinics; Homeostasis; Hypertension, Pulmonary; Hypertrophy, Right Ventricular; Imatinib Mesylate; Iron; Iron Deficiencies; Liver; Male; Maltose; Piperazines; Pulmonary Artery; Pyrimidines; Rats, Sprague-Dawley; Signal Transduction; Time Factors; Transferrin; Vascular Remodeling