Systematic review and meta‐analysis of iron therapy in anaemic adults without chronic kidney disease: updated and abridged Cochrane review

Abstract

Anaemia is increasingly recognized as having an independent impact upon patient outcomes in cardiac disease. The role of novel iron therapies to treat anaemia is increasing. This systematic review and meta-analysis assesses the efficacy and safety of iron therapies for the treatment of adults with anaemia. Electronic databases and search engines were searched as per Cochrane methodology. Randomized controlled trials (RCTs) of iron vs. inactive control or placebo, as well as alternative formulations, doses, and routes in anaemic adults without chronic kidney disease or in the peri-partum period were eligible. The primary outcome of interest was mortality at 1 year. Secondary outcomes were blood transfusion, haemoglobin levels, quality of life, serious adverse events, and length of hospital stay. A total of 64 RCTs (including five studies of heart failure patients) comprising 9004 participants were included. None of the studies was at a low risk of bias. There were no statistically significant differences in mortality between iron and inactive control. Both oral and parenteral iron significantly reduced the proportion of patients requiring blood transfusion compared with inactive control [risk ratio (RR) 0.66, 95% confidence interval (CI) 0.48-0.90; and RR 0.84, 95% CI 0.73-0.97, respectively]. Haemoglobin was increased more by both oral and parenteral iron compared with inactive control [mean difference (MD) 0.91 g/dL, 95% CI 0.48 to 1.35; and MD 1.04, 95% CI 0.52 to 1.57, respectively], and parenteral iron demonstrated a greater increase when compared with oral iron (MD 0.53 g/dL, 95% CI 0.31-0.75). In all comparisons, there were no differences in the results comparing patients with and without heart failure. Both oral and parenteral iron are shown to decrease the proportion of people who require blood transfusion and increase haemoglobin levels, without any benefit on mortality.

Prevalence and clinical impact of iron deficiency and anaemia among outpatients with chronic heart failure: The PrEP Registry

“…A recent meta-analysis involving five trials, which evaluated intravenous iron therapy in iron-deficient patients with systolic heart failure, confirmed that this treatment improves clinical outcomes, exercise capacity, and quality of life, and to alleviate HF symptoms [26]. In line with these results, another meta-analysis showed that iron supplementation reduced the need for blood transfusions and increased haemoglobin levels in patients with chronic kidney disease or in the peri-partal period [27]. The recently published Oral Iron Repletion effects ON Oxygen UpTake in Heart Failure (IRONOUT) trial has underscored missing benefit of oral iron therapy, as no increase in exercise capacity and only a minimal increase in serum ferritin level were noted after 12 weeks of therapy [28].…”

Iron deficiency anemia in older adults: A review

“…23 The absence of a significant response to oral iron supplementation can be attributed to a IDA misdiagnosis, malabsorption or persistent chronic blood loss that exceeds the amount of iron that can be absorbed from an oral supplement. 24,65,[72][73][74][75] The results of iron therapy for indications other than absolute IDA, such as cancer-related anemia, chronic kidney disease, chronic heart failure, inflammatory anemia and postoperative anemia, are not discussed here. 23,24,26,53,71 Several parenteral iron preparations are available, and the most commonly prescribed preparations are iron sucrose, ferric carboxymaltose and iron dextran.…”

New concepts in iron deficiency anaemia

“…In contrast, older parenteral iron preparations, such as iron dextran, were notorious for being associated with potentially lethal anaphylactic and anaphylactoid reactions. 2 However, as our understanding of the role of hepcidin in blocking the uptake of iron from the intestine has grown and it has become clearer that parenteral iron supplementation may, particularly in patients with inflammation, be preferred, there have been encouraging pharmaceutical developments producing intravenous iron replacement products that do not contain dextran. These can be administered in some cases in relatively high doses, such as 500 mg to 1000 mg in a single infusion, offering the opportunity to replace the total body deficit with one or two infusions.…”

“…Many studies have shown that iron deficiency is associated with a longer length of stay in hospital, 2 cognitive dysfunction, 3 increased risk of falls, 4 and reduced life expectancy. 5 Paradoxically, iron is one of the most abundant minerals on earth and is plentiful in all but the most restricted diets.…”