Heart failure patients who are diagnosed with iron deficiency appear to avoid return trips to the hospital if they are treated with intravenous ferric carboxymaltose to replete iron stores, researchers reported at the 2020 scientific sessions of the American Heart Association, writes MedPage. Findings of the journal article in The Lancet may change treatment guidelines.
In the Affirm-AHF trial, patients treated with ferric carboxymaltose had a relative risk reduction of 21% in the primary composite endpoint of hospitalisation and cardiovascular death when compared with patients who received placebo (P=0.059), reported Professor Piotr Ponikowski of Wroclaw Medical University in Poland.
Ed Susman of MedPage reported on 13 November 2020 that the result was primarily driven by a reduction in hospitalisations – which achieved statistical significance with a relative risk reduction of 26% (P=0.013).
This result was achieved with only one or two injections in 80% of the patients in the ferric carboxymaltose group, Ponikowski said at an American Heart Association press conference.
He said that the COVID-19 epidemic had an impact on the trial, and the researchers performed an overall analysis as well as a sensitivity analysis that was based on results before the pandemic set in. This pre-COVID-19 analysis found a 25% relative risk reduction in the primary endpoint which did achieve statistical significance (P=0.024).
"Treatment with ferric carboxymaltose was safe and well-tolerated," Ponikowski said. "The pre-COVID-19 sensitivity analyses revealed statistically significant differences in favour of ferric carboxymaltose for the primary and secondary endpoints.
“Administration of ferric carboxymaltose in patients with heart disease and left ventricular ejection fraction of 50% or less, stabilised after an episode of acute heart failure reduces the risk of subsequent heart failure hospitalisations."
According to MedPage, the Affirm-AHF trial enrolled 1,108 patients in 15 countries who were being discharged after hospitalisation for acute heart failure and were found to have
iron deficiency during their hospital stay. Participants' average age was 71 and 56% were men, with average heart ejection fraction measures of 33%.
After their heart condition was stabilised, patients received either intravenous ferric carboxymaltose, dosed according to the level of iron deficiency, or placebo infusion during the following 24 weeks.
"This is the first study demonstrating the benefits of iron supplementation initiated in stabilised patients hospitalised for acute heart failure, and only two doses were needed in the vast majority of patients," Ponikowski said, the MedPage story continues.
"Health care professionals should screen patients with heart failure for the presence of iron deficiency, and intravenous iron should be considered for those with iron deficiency and ejection fraction of 50% or lower."
Likely to change treatment guidelines
American Heart Association discussant Dr Nancy Sweitzer of the University of Arizona, Tucson, said, the study is likely to change treatment guidelines.
"The trial demonstrates, in more than 1,100 patients, that intravenous ferric carboxymaltose treatment in iron deficient patients hospitalised with heart failure reduces subsequent hospitalisations without an impact on mortality," she said.
She noted that Affirm-AHF "targeted one of the highest risk populations we have in heart failure", MedPage reports. She noted that the patients with heart failure and iron deficiency tend to be older, have more comorbidities, have longer hospital stays and are more frequently re-admitted due to heart failure complications.
Ponikowski disclosed relevant relationships with Vifor Pharma (which sponsored the trial), Amgen, Bayer, Novartis, Boehringer Ingelheim, Abbott Vascular, Merck, Pfizer, Servier, AstraZeneca, Berlin Chemie, Cibiem, Renal Guard Solutions, Bristol Myers Squibb and Impulse Dynamics. Other authors also reported relationships with numerous commercial entities. Sweitzer disclosed relevant relationships with Merck, Novartis and MyoKardia.
Ferric carboxymaltose for iron deficiency at discharge after acute heart failure: a multicentre, double-blind, randomised, controlled trial
The Lancet. 13 November 2020
Piotr Ponikowski, Bridget-Anne Kirwan, Stefan D Anker, Theresa McDonagh, Maria Dorobantu, Jaroslaw Drozdz et al.
Intravenous ferric carboxymaltose has been shown to improve symptoms and quality of life in patients with chronic heart failure and iron deficiency. We aimed to evaluate the effect of ferric carboxymaltose, compared with placebo, on outcomes in patients who were stabilised after an episode of acute heart failure.
AFFIRM-AHF was a multicentre, double-blind, randomised trial done at 121 sites in Europe, South America, and Singapore. Eligible patients were aged 18 years or older, were hospitalised for acute heart failure with concomitant iron deficiency (defined as ferritin <100 μg/L, or 100–299 μg/L with transferrin saturation <20%), and had a left ventricular ejection fraction of less than 50%.
Before hospital discharge, participants were randomly assigned (1:1) to receive intravenous ferric carboxymaltose or placebo for up to 24 weeks, dosed according to the extent of iron deficiency. To maintain masking of patients and study personnel, treatments were administered in black syringes by personnel not involved in any study assessments.
The primary outcome was a composite of total hospitalisations for heart failure and cardiovascular death up to 52 weeks after randomisation, analysed in all patients who received at least one dose of study treatment and had at least one post-randomisation data point.
Secondary outcomes were the composite of total cardiovascular hospitalisations and cardiovascular death; cardiovascular death; total heart failure hospitalisations; time to first heart failure hospitalisation or cardiovascular death; and days lost due to heart failure hospitalisations or cardiovascular death, all evaluated up to 52 weeks after randomisation.
Safety was assessed in all patients for whom study treatment was started. A pre-COVID-19 sensitivity analysis on the primary and secondary outcomes was prespecified.
Between March 21, 2017, and July 30, 2019, 1525 patients were screened, of whom 1132 patients were randomly assigned to study groups.
Study treatment was started in 1110 patients, and 1108 (558 in the carboxymaltose group and 550 in the placebo group) had at least one post-randomisation value. 293 primary events (57·2 per 100 patient-years) occurred in the ferric carboxymaltose group and 372 (72·5 per 100 patient-years) occurred in the placebo group (rate ratio [RR] 0·79, 95% CI 0·62–1·01, p=0·059). 370 total cardiovascular hospitalisations and cardiovascular deaths occurred in the ferric carboxymaltose group and 451 occurred in the placebo group (RR 0·80, 95% CI 0·64–1·00, p=0·050).
There was no difference in cardiovascular death between the two groups (77 [14%] of 558 in the ferric carboxymaltose group vs 78 [14%] in the placebo group; hazard ratio [HR] 0·96, 95% CI 0·70–1·32, p=0·81). 217 total heart failure hospitalisations occurred in the ferric carboxymaltose group and 294 occurred in the placebo group (RR 0·74; 95% CI 0·58–0·94, p=0·013).
The composite of first heart failure hospitalisation or cardiovascular death occurred in 181 (32%) patients in the ferric carboxymaltose group and 209 (38%) in the placebo group (HR 0·80, 95% CI 0·66–0·98, p=0·030).
Fewer days were lost due to heart failure hospitalisations and cardiovascular death for patients assigned to ferric carboxymaltose compared with placebo (369 days per 100 patient-years vs 548 days per 100 patient-years; RR 0·67, 95% CI 0·47–0·97, p=0·035). Serious adverse events occurred in 250 (45%) of 559 patients in the ferric carboxymaltose group and 282 (51%) of 551 patients in the placebo group.
In patients with iron deficiency, a left ventricular ejection fraction of less than 50%, and who were stabilised after an episode of acute heart failure, treatment with ferric carboxymaltose was safe and reduced the risk of heart failure hospitalisations, with no apparent effect on the risk of cardiovascular death.
MedPagearticle – Pumping Iron: IV Supplement Helps Heart Failure Patients
Article in The Lancet – Ferric carboxymaltose for iron deficiency at discharge after acute heart failure: a multicentre, double-blind, randomised, controlled trial