United Kingdom treatment of iron deficiency in heart failure: are we missing opportunities?

Br J Cardiol 2021;28(suppl 1):S7–S9doi:10.5837/bjc.2021.s02 Leave a comment
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This supplement was fully funded by an unrestricted grant from Vifor Pharma UK Limited. The content of the articles was independently developed by the authors and according to a brief agreed between Vifor Pharma UK and the BJC. Vifor Pharma reviewed the final version of each article for Code Compliance only. Prescribing information for Ferinject ▼ (ferric carboxymaltose) can be found here.

Job code: UK-FCM-2100010
Date of preparation: January 2021

Iron deficiency in patients with reduced ejection fraction heart failure is common. Restoration of iron levels has been shown to improve quality of life, exercise tolerance and reduce hospitalisations. Oral iron therapy has been shown not to improve iron stores. Using intravenous iron improves iron stores, however, there is disparity in guidelines, with no mention within the National Institute of Health and Care Excellence guidelines, while the European Society Cardiology guidance recommends consideration of treating patients with iron deficiency with intravenous iron.

Across the UK, heart failure services vary hugely with care being delivered within primary care, secondary care or a combination of both. Some services are based mainly in primary care while others are primarily provided in hospitals. There is a third group with a combination of care delivered by primary care and hospitals. Therefore, when developing an intravenous iron service, there is no one model that fits all. In this manuscript, we provide an overview of iron deficiency in heart failure patients along with describing the key considerations when setting up an intravenous iron therapy service for heart failure patients as well as our experience at the University Hospital of North Midlands.

Introduction

Iron deficiency in patients with heart failure with reduced ejection fraction (HFrEF) is common, affecting 60% of patients with hospitalisation for heart failure or worsening heart failure in the outpatient setting.1 Patients with heart failure are iron deficient for multiple reasons, including poor nutrition, malabsorption, reduced intracellular uptake of iron and blood loss.2 Two meta-analyses of randomised-controlled trials (RCTs) have shown the benefits of restoring iron levels in improving quality of life, exercise tolerance and reducing hospitalisation for heart failure, although, as of yet, no mortality benefit has been seen.3,4

Giving oral supplementary iron has not been shown to improve iron stores,5 hence, the need to use intravenous (IV) iron. The evidence for the use of IV iron in heart failure has been demonstrated in three RCTs,6-8 showing that IV ferric carboxymaltose in patients with chronic heart failure and iron deficiency improves functional capacity and quality of life with an acceptable side effect profile.7,8

However, although there is evidence that treating iron deficiency in patients with HFrEF can improve quality of life, exercise tolerance and reduce hospital admissions, measurement of iron levels in these patients remains sporadic. Services vary across the country with some patients given IV iron by dedicated heart failure teams, other heart failure services requiring renal or gastroenterology teams to support IV iron and other areas having no facilities at all to treat their patients.

There is disparity in guidelines, with no mention within the National Institute of Health and Care Excellence (NICE) guidance10 for use of IV iron for treatment of patients, whereas the European Society of Cardiology (ESC) guidance recommends consideration of treating patients with iron deficiency.11 Furthermore, the lack of mortality benefit seen in the current published data leaves many clinicians questioning the benefits of treating iron deficiency and, therefore, investing in local IV iron services.

The optimum treatment for iron deficiency in heart failure

Although there remain no published data for improvement in prognosis for treating patients for iron deficiency, there are benefits with regards to symptom relief and reduced hospitalisations. While treatments that show mortality benefit are important, among patients with heart failure and clinicians managing patients with heart failure, symptomatic improvement is of a high priority.

The optimal treatment for iron deficiency in heart failure is correction of the iron deficiency and improvement of the exercise capacity and quality of life of patients. However, it is important that healthcare professionals are aware that the ESC guidelines recommend that the serum ferritin <100 µg/L or ferritin between 100–299 µg/L and transferrin saturation <20% is grounds for IV ferric carboxymaltose,11 and that every contact, whether as an inpatient admission, outpatient clinic or general practitioner consultation, is an opportunity to identify iron deficiency and potentially improve the quality of life of patients with HFrEF by treating it. Therefore, when patients are identified to have heart failure, full blood counts and iron studies should be requested. Like management of iron-deficiency anaemia in the general adult, it is important to also consider potentially reversible or treatable causes, such as low iron bioavailability of the diet, malabsorption from coeliac disease, and chronic blood loss.12

How to set up an optimum heart failure iron treatment service using the experience of authors’ centre

Across the UK, heart failure services vary hugely. Some services are based mainly in primary care, while others are primarily provided in hospitals, and there is a third group where there is a combination of care delivered by primary care and hospitals. Therefore, when developing an IV iron service, there is no one model that fits all. A heart failure iron treatment service can be set up as an independent service or as an integrated service within heart failure care. However, there remains a number of key considerations when developing an IV iron service. We will highlight a few of the key areas as follows:

  • It is important to understand the aims of the service are to treat patients with HFrEF that have iron deficiency to improve symptoms and quality of life.
  • In planning to start a service, the provider needs to be aware of the number of patients they are likely to be treating and also the logistics of where and who will be giving the IV iron. This also guides business cases and funding requirements.
  • There needs to be understanding of where the patients will receive treatment, be it in primary care or hospital. The IV therapy can be delivered specifically within heart failure specialist units or integrated into services for other specialities delivering IV iron.
  • There need to be clear guidelines and protocols in place, not only for selecting patients for treatment, but also for administering IV iron therapy, with healthcare professionals capable of delivering treatment, and treating any potential complications, such as anaphylaxis.
  • There needs to be appropriate staff training and competencies, which would ensure that all staff delivering IV iron are aware of potential complications and how to safely manage them.
  • There should be ongoing data collection to support service development and regular audits. Ideally, this should include quality of life, as well as hospitalisation data.
  • There needs to be appropriate funding in place.
  • There needs to be involvement of allied health professionals, such as hospital pharmacists.
  • There needs to be patient information available and also clear clinical information, such as discharge letters for general practitioners.

An independent iron treatment service in heart failure can be helpful in settings where there is a large local population with heart failure and there could be a significant demand for IV iron therapy. Integrating iron services with routine heart failure care may be less resource intensive but requires training, developing protocols for staff and education of health professionals about the service. To determine the ideal service for a centre, clinical audit and health service evaluation can be helpful.

Local data and development of guideline

Prior to initiating the IV iron service at University Hospital North Midlands (UHNM), a service evaluation was performed to understand the likely demand for IV iron. This evaluation reviewed the medical records of 1,086 patients hospitalised for heart failure and found that 444 patients had an ejection fraction <45%, and there were very low rates of assessment of iron status in patients with heart failure (292/1,086, 29.7%). Within this group, 208 (71%) were found to be iron deficient and fulfilled the ESC guidelines for IV iron treatment. This service evaluation aided our understanding of the demand for the service and its potential impact.

We developed local guidelines based on the ESC guidance criteria for selection of patients that are appropriate for IV iron. Heart failure patients with reduced ejection fraction have ferritin and transferrin saturation measured when they make first contact with the service either as inpatients, outpatients or follow-up visits. Referrals also come from the community heart failure teams and can be made during the combined heart failure multi-disciplinary team.

Service at UHNM

UHNM has a well-developed ambulatory heart failure service with referrals from the in-hospital and community heart failure teams. We have an ideal arena for IV iron therapy. Prior to initiation of the service there was education and training for the heart failure team focusing on patient selection and administering of IV iron. Heart failure nurses identify iron deficiency during their consultations with heart failure patient, whether in clinic or as inpatients. 

The service includes a heart failure specialist nurse who has been trained to administer IV iron therapy as a day-case procedure for patients living in the community, and also provide guidance for treatment for hospitalised patients. In addition to the personnel delivering the therapy, we have space in the ambulatory unit where outpatients can be cannulated, bloods can be taken, observations can be measured and the patient monitored as they receive IV iron therapy as an outpatient. Assuming no untoward events, patients can remain at the unit for an hour before discharge home on the same day. A discharge letter is prepared for the clinical episode associated with the treatment and it is sent to the general practitioner.

Typically, patients are given the appropriate dose of IV iron and, if required, a further dose is given two weeks later. Patients normally have repeat iron levels at three to six months, which we try to correlate with follow-up appointments. At this time, we also try to collect quality-of-life data. Ongoing follow-up includes review in the heart failure clinic and blood tests before discharge to the general practitioner, unless there are ongoing patient needs.

Rationale for this approach

While oral iron salts are often used because of their low cost and ease of administration, we use IV iron therapy as first line. The reason IV iron replacement is used in our heart failure patients is because there is poor compliance with oral iron due to gastrointestinal side effects and absorption from the gastrointestinal tract may be limited by many foods, medications, gut oedema and upregulation of hepcidin.2 In addition, from our experience we found that oral iron requires a long time to correct iron deficiency and IV iron therapy can correct iron deficiency relatively quickly and is well tolerated. For some patients with heart failure, particular those with limited long-term prognosis, any measure to rapidly potentially improve quality of life can be helpful for patient’s quality of life.

Audit of service

All patients coming through the ambulatory heart failure service are recorded and we collect baseline data including measurements of quality of life. This information is required for the local commissioners and the cardiology directorate. There is ongoing service evaluation of the IV iron service, which aids in understanding the impact on of the service and supports local commissioning.

From our local data, 14 patients received IV iron therapy since February 2020. The age range of these patients was 53 to 88 years and their average baseline ferritin and transferrin saturation were 90 ± 71 and 9.1 ± 5.2, respectively. Aside from one patient who died from coronavirus 2019, all other patients are alive and discharged with no adverse reactions to IV iron therapy.

How is the treatment of iron deficiency organised in the UK

IV iron services across the UK are varied, with some regions having well-developed and integrated services, while other heart failure services do not currently have the provision to treat iron-deficient patients. Furthermore, although research shows a quality-of-life improvement, the lack of mortality benefit likely hinders commissioning of IV iron services, and setting up services is a challenge at present. Currently, a multi-centre randomised trial, IRONMAN10 is investigating whether IV iron treatments in iron-deficient heart failure patients has an impact upon hospitalisation rates, cardiovascular morbidity and all-cause mortality. If a clear benefit is shown it may alter NICE guidance, and may enable a more streamlined and efficient iron-deficiency heart failure treatment service to be widely available across the UK.

Conclusion

The use of IV iron for the treatment of iron-deficient patients with reduced ejection heart failure across the UK is variable. The lack of mortality data and NICE guidance means commissioning IV services is challenging. However, it is important for clinicians to realise the benefits for symptomatic improvement, quality of life and potential reduction in hospitalisations. A survey performed by Pumping Marvellous highlighted that patients prioritise quality of life above prognosis as common worries. By not providing IV iron as a treatment for our heart failure patients, we are potentially failing our patients and missing an opportunity to improve their quality of life.

Key messages

  • The use of intravenous (IV) iron for the treatment of iron-deficient patients with heart failure with reduced ejection fraction (HFrEF) in the UK is variable.
  • The lack of mortality data and National Institute of Health and Care Excellence (NICE) guidance around the use of IV iron in this setting means commissioning IV services is challenging
  • However, it is important for clinicians to realise the benefits of IV iron for symptomatic improvement, quality of life and potential reduction in hospitalisations
  • By not providing IV iron as a treatment for our heart failure patients, we are potentially failing our patients and missing an opportunity to improve their quality of life

Conflicts of Interest

None declared.

Chun Shing Kwok
Clinical Lecturer in Cardiology and Cardiology Registrar

Sarah McDermott
Heart Failure Specialist Nurse

Sadie Bennett
Clinical Scientist

Simon Duckett
Consultant Cardiologist
(simon.duckett@uhnm.nhs.uk)

Royal Stoke University Hospital, Newcastle Road, Stoke-on-Trent, ST4 6QG

Articles in this supplement

Prevalence, causes, diagnosis and guidelines for treatment

Intravenous iron therapies and their differences

Iron deficiency – the invisible comorbidity in HF: prioritising QoL as a target for treatment

Conclusions

References

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2. Kocyigit D, Gurses KM. Iron deficiency and its treatment in heart failure: indications and effect of prognosis. E-Journal of Cardiology Practice 2016;14. Available from: https://www.escardio.org/Journals/E-Journal-of-Cardiology-Practice/Volume-14/Iron-deficiency-and-its-treatment-in-heart-failure-indications-and-effect-on-prognosis

3. Anker SD, Kirwan BA, van Vedlhuisen DJ et al. Effect of ferric carobxymaltose on hospitalisations and mortality rates in iron-deficient heart failure patients: an individual patient data meta-analysis. Eur J Heart Fail 2018;20:125–33. https://doi.org/10.1002/ejhf.823

4. Jankowska EA, Tkaczyszyn M, Suchoki T et al. Effects of intravenous iron therapy in iron-deficient patients with systolic heart failure: a meta-analysis of randomized controlled trials. Eur J Heart Fail 2016;18:786–95. https://doi.org/10.1002/ejhf.473

5. Lewis GD, Malhotra R, Hernandez AF et al. Effect of oral iron repletion on exercise capacity in patients with heart failure with reduced ejection fraction and iron deficiency. JAMA 2017;317:1958–66. https://doi.org/10.1001/jama.2017.5427

6. Anker SD, Colet JC, Filippatos G et al. Ferric carboxymaltose in patients with heart failure and iron deficiency. N Engl J Med 2009;361:2436–48. https://doi.org/10.1056/NEJMoa0908355

7. Ponikowski P, van Veldhuisen DJ, Comin-Colet J et al. Beneficial effects of long-term intravenous iron therapy with ferric carboxymaltose in patients with symptomatic heart failure and iron deficiency. Eur Heart J 2015;36:657–68. https://doi.org/10.1093/eurheartj/ehu385

8. Van Veldhuisen DJ, Ponikowski P, van der Meer P et al. Effect of ferric carboxygmaltose on exercise capacity in patients with chronic heart failure and iron deficiency. Circulation 2017;136:1374–83. https://doi.org/10.1161/CIRCULATIONAHA.117.027497

9. National Institute for Health and Care Excellence (NICE). Chronic heart failure in adults: diagnosis and management. London: NICE, 2018. Available from: www.nice.org.uk/guidance/ng106 [accessed 20 July 2020].

10. Ponikowski P, Voors AA, Anker SD et al. 2016 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J 2016;37:2129–200. https://doi.org/10.1093/eurheartj/ehw128

11. Johnson-Wimbley TD. Diagnosis and management of iron deficiency anemia in the 21st century. Therap Adv Gastroenterol 2011;4:177–84. https://doi.org/10.1177/1756283X11398736

12. Clinicaltrials.gov. Intravenous iron treatment in patients with heart failure and iron deficiency: (IRONMAN). Available at: https://clinicaltrials.gov/ct2/show/NCT02642562

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