Hello.
My name is Paul Kalra.
I'm consultant cardiologist and heart failure
specialist at Portsmouth Hospital's University NHS
Trust in the United Kingdom.
And I was chief investigator for IRONMAN, which was a
trial that was funded by the British Heart Foundation.
So IRONMAN was a randomized trial of
intravenous ferric derisomaltose and usual care versus usual
care alone in patients with heart failure,
a reduced ejection fraction and an iron deficiency.
We presented this and published this in 2022
and the main trial showed that intravenous ferric
derisomaltose reduced the risk of the primary endpoint
which was a combination of cardiovascular death and
recurrent heart failure hospitalization by 18%.
The p value was 0.07.
But our trial was markedly impacted by COVID and
when we did a prespecified COVID sensitivity analysis we
had a rate ratio of 0.75 and the
p value of less than 0.05.
The main benefit appeared to be on
a reduction in heart failure hospitalization.
So we now have a number
of secondary analysis from IRONMAN.
Firstly, we have been interested in looking at the impact
of ferric derisomaltose on infections and the reason for this
is that previous trials of intravenous iron in other disease
areas have questioned as to whether it might be associated
with a higher risk of infection.
But they've had major limitations because this wasn't a
prespecified analysis and as such, subject to potential reporting
bias in IRONMAN, all deaths and hospitalizations were
blindly adjudicated and this was a prespecified endpoint and
we found that there was no excess risk of
infections as a cause of hospitalization or death.
And in fact, when you look to time
to first event there was a 21% reduction
with ferric derisomaltose that approached statistical significance
of p-value of 0.055.
What we did find looking at COVID adverse
events was there was a 60% statistical reduction
in COVID-related events with intravenous iron.
So I think that the benefits of these data are
when we are speaking to our patients discussing the risk
benefit of a drug like intravenous iron, we now have
increasing data about the safety profile, if you like, for
intravenous iron and the fact that there's no excess risk
with infections is really good news.
We've also had other presentations having a deeper
dive into quality of life at four months
and consistent with previous studies with the different
intravenous iron, ferric carboxymaltose, that have shown benefits
on quality of life, we found very similar
findings at four months with the Minnesota living
with heart Failure questionnaire.
That was primarily driven by
improvements in the physical domain.
And what we've seen is as patients had lower TSATs
then their quality of life was worse at baseline, but
they appeared to have more to gain from intravenous iron.
And similarly, the patients with moderate anaemia as opposed
to mild anaemia or normal haemoglobin again had impaired
quality of life at baseline and they appeared to
have more to gain from intravenous iron in terms
of benefits on quality of life.
So, again, that's good news.
We can tell our patients seems to benefit on
the reducing the risk of heart failure hospitalization, but
also an improvement in quality of life.
And finally, we've looked across the ages, age
of patients, that is, we had a quarter
of our patients were 79 or older.
And again, what is important here, because these
are people that we're seeing in real life,
day to day clinical pathways, the benefits seem
to be maintained in that older age group.
So I think the important thing is if you've got
a patient with heart failure and any degree of reduced
ejection fraction, please screen them for iron deficiency.
If you don't look for it, you're not going to find it.
And when present, then correction with high dose
intravenous iron is a good way to help
patients feel better and reduce the risk of
heart failure hospitalization, and there's a low risk
of adverse events with intravenous iron.
So there are a few things we still need to establish.
One is, is there a better marker for
iron deficiency and the potential response to intravenous
iron than we're using at the moment?
These have been arbitrary definitions and I think the
data that we're seeing from IRONMAN and pooled analysis
with other studies is that a transferring saturation of
less than 20% is particularly important here.
I think we need to understand more
about the potential benefits in patients with
heart failure and preserved ejection fraction.
We haven't got data on that group at the moment
and hopefully we'll see some later on this year.
And then finally, whilst there were
numerically fewer cardiovascular deaths in IRON
MAN, it didn't reach statistical significance.
There's another trial called Heart Fit that we'll
present later this year and I think looking
at a pooled analysis of trials will be
very interesting in that respect.