AFFIRM-AHF: IV iron cuts risk of HF readmissions

Intravenous (IV) iron supplementation with ferric carboxymaltose (FCM) reduces the risk of subsequent hospitalization for heart failure (HF) in iron-deficient patients after an episode of acute HF, shows the AFFIRM-AHF trial presented at the AHA 2020 Meeting.

“Iron deficiency can be easily detected using a simple blood test and is now an important therapeutic target,” said lead investigator Dr Piotr Ponikowski from Wroclaw Medical University in Wroclaw, Poland.

“Healthcare professionals should screen patients with HF for the presence of iron deficiency, and IV iron should be considered for those with iron deficiency and ejection fraction of 50 percent or lower,” he highlighted.

At 52 weeks, IV FCM reduced the composite primary endpoint of total hospitalizations for HF and cardiovascular (CV) mortality by 21 percent compared with placebo (rate ratio [RR], 0.79; p=0.059). [Lancet 2020;396:1895-1904]

While the composite primary outcome did not reach statistical significance, risk reduction in the component of HF hospitalization was significant, by 26 percent (RR, 0.74; p=0.013) — which according to Ponikowski, was the main driver of the reduction in the composite primary outcome.

The benefit on HF hospitalizations was seen with only one or two FCM injections in a majority of the patients (80 percent), irrespective of anaemia status, reported Ponikowski.

There was no effect on the component of CV mortality (hazard ratio, 0.96; p=0.809), as expected.

As follow-up of patients was disrupted by the COVID-19 outbreak, the investigators also performed a prespecified sensitivity analysis censoring patients in each country when the first case of COVID-19 was reported.

The sensitivity analysis revealed that the risk reductions were statistically significant for the primary composite endpoint (RR, 0.75; p=0.024) as well as total HF hospitalizations (RR, 0.70; p=0.005).

Potentially practice changing

“The million-dollar question, of course, is what will the results of this study mean for the guidelines: I think they probably will change the guidelines,” said invited discussant Dr John McMurray from University of Glasgow, Glasgow, UK, who called for a stronger recommendation for IV iron in this population. 

Thus far, use of IV iron supplementation was given a class IIb recommendation in the 2017 ACC/AHA* guidelines and a class IIa recommendation in the 2016 ESC guidelines for HF, with wordings such as “might be reasonable” or “should be considered” in the respective guidelines.

Press briefing panellist, Dr Nancy Sweitzer from the University of Arizona's Sarver Heart Center in Tucson, Arizona, US, agreed, saying AFFIRM-AHF looked at “one of the highest risk populations in HF” and represents “an important trial likely to change guidelines.”

Iron-deficient patients tend to be older people with more comorbidities and higher readmission rates, she pointed out.  

Another panellist, Dr Marc Pfeffer of Harvard Medical School in Boston, Massachusetts, US, highlighted the importance of showing that iron deficiency is a risk factor in these patients.

“It’s one thing to have a risk factor; it’s another to be a modifiable risk factor and I think that’s what’s so exciting about this,” he said.

“We only need to remember, we only need to assess it, and we have a very, very simple tool in our hands. We just need to measure two biomarkers, transferrin saturation and ferritin — that’s all,” explained Ponikowski.

IV route is key

While multiple trials have shown benefits of IV iron supplementation in improving symptoms, exercise capacity, and quality of life in HF patients with iron deficiency, the benefit was not replicated with oral iron supplementation in the IRONOUT trial.

“So it seems if we are to replace iron, it needs to be done using IV therapy,” said McMurray.

In the double-blind, phase IV AFFIRM-AHF study, 1,132 patients (mean age 71 years, female 44.5 percent) were randomized 1:1 to receive a FCM bolus injection or normal saline prior to discharge from hospital for an acute HF episode. Subsequently, treatment was given as required, up to 24 weeks after randomization.