Primary Care

Iron is an essential nutrient for both physical and mental wellbeing, and yet iron deficiency is a common clinical problem.1 Although women and children are most at risk,2 chronic disease can leave some patients susceptible to iron deficiency3. This is true of patients with chronic heart failure, for several reasons:

  • Inflammation and malabsorption: Chronic heart failure affects many organs, including the gastrointestinal tract.4 A generalised state of inflammation, characteristic of heart failure, causes hepcidin release, blocking intestinal absorption.3 Reduced blood flow to the gut and an increased bowel wall thickness also act to reduce the ability to absorb iron.4
  • Medication: Chronic use of aspirin or non-steroidal anti-inflammatory drugs (NSAIDs) in patients with heart failure can trigger blood loss via the intestinal tract, leading to iron deficiency.5 Drug-induced anorexia may also be caused by angiotensin-converting enzyme inhibitors, reducing iron intake.6
  • Reduced dietary intake: Chronic heart failure patients may adjust their diet, and consequently reduce their iron intake, because of reduced strength/breathlessness and gastrointestinal symptoms such as nausea, early feeling of satisfaction, or loss of appetite resulting from oedema in the stomach and intestine.6

IMPACT OF IRON DEFICIENCY IN CHRONIC HEART FAILURE

Patients with chronic heart failure and iron deficiency will experience a reduced quality of life and reduced exercise tolerability. Not only that, they will also be more likely to need a heart transplant and are at greater risk of death than those patients without iron deficiency.10

Event-free survival in patients with chronic heart failure with and without iron deficiency


Figure 1: Event-free, 8-year survival for patients with chronic heart failure with and without iron deficiency. Differences in mortality rates were significant at 6 months, and remained so through-out follow-up (p<0.001).7

IMPACT OF ANAEMIA IN CHRONIC HEART FAILURE

TREATING IRON DEFICIENCY AND ANAEMIA IN CHRONIC HEART FAILURE

The European Society of Cardiology guidelines recommend evaluation of iron status in all patients suspected of having heart failure. The underlying cause of iron deficiency and/or anaemia should be identified and treated where necessary; for example, renal disease, occult bleeding or deficiencies other than iron.13 Once the extent and cause of the patient’s iron deficiency has been established treatment options can be considered.

  • Dietary changes: Patients with chronic heart failure may have a poor or restricted diet caused by loss of appetite or dietary recommendations for a comorbidity such as renal disease.13 Advice on how to increase their intake of iron-rich foods, and coordinating foods to get maximum iron absorption, could help manage low levels of iron deficiency.
  • Oral iron supplements: Oral iron is inexpensive and  is widely used to treat iron deficiency despite its low bioavailability – in heart failure patients approximately only 5% of each dose is absorbed.13 Gastrointestinal side-effects are common, reported in up to 60% of patients, and often lead to poor compliance. Oral iron is generally considered unsuitable for patients with impaired gastrointestinal absorption, as is the case in heart failure.Studies of oral iron in heart failure patients have found no changes in haemoglobin, symptom severity and exercise tolerance for patients receiving iron, however, the evidence is limited.13
  • Erythropoiesis-stimulating agents (ESAs):ESAs such as darbepoetin alfa and epoetin are used to treat anaemia, often in patients with chronic kidney disease. However, as erythropoiesis requires iron, treatment is only useful if iron stores are replete. Epoetin can negatively affect iron absorption from the gut,a process already aggravated in chronic heart failure patients, therefore intravenous iron is recommended as the best route for iron administration to support epoetin use.5
  • Intravenous iron: Original formulations include iron sucrose, low and high molecular weight iron dextran and ferric gluconate. More recent products such as ferric carboxymaltose, iron isomaltoside 1000,and ferumoxytol are more stable and allow rapid replenishment of iron levels, without the formation of large amounts of non-transferrin-bound iron (NTBI). Delivering iron intravenously also avoids any absorption disorders in the gut.13

Intravenous iron is the preferred choice for patients with chronic heart failure due to their reduced absorption, already high medication burden and high levels of hepcidin, which can inhibit the release of stored iron.13

BENEFITS OF TREATING IRON DEFICIENCY IN CHRONIC HEART FAILURE

A recent meta-analysis of individual patient data from trials of ferric carboxymaltose compared with placebo in patients with chronic heart failure showed a significant reduction in the risk of recurrent hospitalisations or death due to cardiovascular events in the ferric carboxymaltose group.14

Another meta-analysis of randomized controlled trials of intravenous iron (ferric carboxymaltose or iron sucrose) in patients with heart failure and iron deficiency reports improvements in NYHA class, 6-minute walking test and quality of life scores.15