Intravenous iron reduces the risk of recurrent hospitalisation and cardiovascular death in people with chronic heart failure and iron deficiency, a UK clinical trial has shown.
Long-term treatment with IV ferric derisomaltose improved symptoms and reduced heart failure hospitalisations among in patients with heart failure, reduced ejection
fraction, and iron deficiency, according to results from the IRONMAN (Effectiveness of Intravenous iron treatment vs. standard care in patients with heart failure and iron deficiency) study presented at the American Heart Association’s Scientific Sessions 2022.
The study builds on evidence from smaller, short term studies that used ferric carboxymaltose an showed benefit of IV iron in patients hospitalised with acute heart failure who had iron deficiency.
The study investigators said iron deficiency was an important comorbidity in patients in around 40% of patients with chronic heart failure, associated with a reduction in both quality of life and exercise capacity, and an increase in hospital admissions for heart failure and mortality, irrespective of the presence of anaemia
“Despite several great therapeutic successes in recent decades, many people with heart failure still have symptoms that restrict their daily lives, and the rates of hospital admissions and mortality remain high,” said study investigator Dr Paul Kalra, a consultant cardiologist and heart failure specialist at Portsmouth Hospitals University National Health Service Trust and honorary senior lecturer at the University of Glasgow in the United Kingdom.
“There is an urgent need for new treatments that are safe and affordable.”
Dr Kalra and his colleagues developed the IRONMAN trial to investigate whether long-term administration of IV iron improved outcomes among adults with heart failure (LVEF ≤45% ) and iron deficiency (transferrin saturation less than 20% or serum ferritin less than 100 μg/L ) compared to the current guideline-recommended care that does not include IV iron treatment.
The study was conducted across 70 UK hospital sites and included 1,137 adults, median age 73 years, of whom most were outpatients without recent hospitalisation for heart failure, with.
Those assigned to the IV iron group received additional doses at the one-month review and every four months after if iron deficiency returned. Study participants were followed for a median length of just over 2.5 years, with follow up clinic visits every four months.
After adjusting for disruptions in care during the Covid-19 pandemic, the primary outcome of recurrent hospital admissions for heart failure and cardiovascular death was reduced by 24% in the IV iron group compared to usual care.
The reduction in the primary endpoint was statistically significant (210 primary endpoints [22.3 per 100 patient-years] in the ferric derisomaltose group vs 280 [29.3 per 100 patient-years] in the usual care group; RR 0.76 [95% CI 0.58 to 1.00]; p=0.047).
People in the IV iron group also reported improved well-being based on heart failure-related quality-of-life questionnaires when initially assessed at 4 months, but not when re-assessed at 20 months.
Long-term IV iron use was not associated with greater risk of infection and was associated with significantly fewer serious adverse cardiac events as compared to usual care.
“These results demonstrate that repeated dosing with IV iron is a beneficial, safe and well-tolerated treatment option that may improve the well-being of adults with heart failure and iron deficiency within a few months,” said Dr Kalra said.
He said it was important to highlight that the beneficial results were seen despite the fact that approximately one in six patients randomized to standard care alone received IV iron outside the trial, which likely reduced the level of benefit seen with IV iron in the study.
“This study builds on existing evidence such that intravenous iron may benefit a broad range of people with heart failure, including those who are hospitalized, recently discharged or attending office or out-patient clinic appointments,” he concluded
The findings are published in The Lancet (link here), with an accompanying commentary stating that additional research is needed to establish whether the benefits seen in the IRONMAN trial also extend to patients across the entire heart failure spectrum “to include those with heart failure with preserved ejection fraction or asymptomatic left ventricular dysfunction.
The study investigators said the efficacy of oral iron in patients with heart failure compared with the intravenous preparations had not been studied in large outcome trials. But they noted that parenteral administration of iron was required to correct iron deficiency rapidly and oral iron, even if well absorbed, would take many months to do so.
The trial was funded by the British Heart Foundation and Pharmacosmos.