Research study that involved researchers from the National Heart Centre Singapore (NHCS) together with their partners from Europe, Middle East, and South America. Findings affirmed that iron therapy significantly reduces heart failure hospitalisation and mortality in patients with acute heart failure (HF).
“There have been significant heart failure cases complicated with iron deficiency, resulting in poor quality of life and composite outcomes, with higher risk of hospitalisation and deaths,” said Associate Professor David Sim, Director of Heart Failure Programme from NHCS, and the National Coordinator for Singapore in AFFIRM-AHF.
“About 30 percent of stable heart failure patients and 50 percent of hospitalised patients are found to have anaemia. Therefore, it is crucial to identify this comorbidity in heart failure patients, as some can also be iron deficient without being diagnosed with anaemia.”
Conducted from 2017 to 2020, the AFFIRM-AHF is a multicentre, randomised, double-blind, placebo-controlled trial done at 121 sites in Europe, South America, and Singapore. This trial is the first to evaluate the effect of intravenous iron on morbidity and mortality in patients with iron deficiency and acute heart failure.
The study screened a total of 1525 patients, of whom 1132 were then randomly assigned to study groups. 1110 patients were allocated randomly to the study treatment with 558 in the group given ferric carboxymaltose and 550 in the placebo group. The two groups were then compared based on total cardiovascular hospitalisation, cardiovascular death, total heart failure hospitalizations, and days lost due to heart failure hospitalizations or cardiovascular death. Both groups were given doses of intravenous iron or the placebo over a course of 52 weeks.
Formulation of intravenous iron used was known was ferric caboxymaltose. This formulation is a dark brown colloidal solution of nanoparticles. Participants from both groups were also assessed for efficacy and safety at weeks 4, 12, 36, and 52 through outpatient clinic visits or phone call to the patient.
“[Many] patients may not absorb the iron well when given orally, we do know that patients with heart failure may have issues with absorption of iron through the gut.” Shared Associate Professor Sim at a media briefing for the study.
Associate Professor Sim further explained that previous studies involving oral iron found no associated beneficial outcome among heart failure patients. He also highlighted that this form of intravenous iron is also found to pose less risk of anaphylaxis as compared to other formulations of intravenous iron.
“This newer generation of [intravenous] iron formulation causes less allergic reaction. In our experience at NHCS we have used it in many patients and have not encountered any case of serious allergic reaction with this current formulation,” said Associate Professor Sim.
Based on the results of the trial it was found that there was no effect on cardiovascular death between the group given intravenous iron and the placebo group. However, further analysis demonstrated that within the study population, patients who were given intravenous iron had reduced risk of heart failure hospitalizations as compared to patients who were administered the placebo.
“Iron deficiency is very common among Asian populations with about 60 percent of heart failure patients have it. It is something that can be very easily detected using simple blood test, and it should be assessed in all patients who come to the hospital for acute decompensated heart failure.” Said Associate Professor Sim.
“We know from clinical trials that this is an important therapeutic target because by targeting [iron deficiency], we can [improve] the quality of life and more importantly, reduce heart failure hospitalizations.”
Conclusion and Application of Study Findings
Findings from the study have been translated into recommendations for clinical practice at NHCS, where specific guidelines are implemented to identify and treat iron deficiency in patients with heart failure.
“We are happy that our research findings have been translated into clinical practice, as part of the overall treatment strategy for patients with HF, so that patients can lead a better quality of life and reduce their readmissions to hospitals,” said Associate Professor David Sim, who is also a Senior Consultant from the Department of Cardiology at NHCS.
This multi-national clinical trial has shown that intravenous iron therapy for heart failure patients can significantly reduce re-hospitalization and improve health outcomes, this would translate into reduce burden for healthcare resources.
- Ponikowski, P., Kirwan, B. A., Anker, S. D., McDonagh, T., Dorobantu, M., Drozdz, J., Fabien, V., Filippatos, G., Göhring, U. M., Keren, A., Khintibidze, I., Kragten, H., Martinez, F. A., Metra, M., Milicic, D., Nicolau, J. C., Ohlsson, M., Parkhomenko, A., Pascual-Figal, D. A., Ruschitzka, F., … AFFIRM-AHF investigators (2020). Ferric carboxymaltose for iron deficiency at discharge after acute heart failure: a multicentre, double-blind, randomised, controlled trial. Lancet (London, England), 396(10266), 1895–1904. https://doi.org/10.1016/S0140-6736(20)32339-4